Transglutaminase 2(TG2) inhibitors

文档序号：638819 发布日期：2021-05-11 浏览：27次中文

阅读说明：本技术 转谷氨酰胺酶2(tg2)抑制剂 (Transglutaminase 2(TG2) inhibitors ) 是由 D.坎普贝尔 J.查普曼 M.H.张 T.R.迪莱蒙多 S.G.杜伦于 2019-08-09 设计创作，主要内容包括：本文描述了抑制转谷氨酰胺酶2(TG2)的化合物和包含此类化合物的药物组合物。本文还描述了单独或与其他化合物组合使用此类TG2抑制剂来治疗从TG2抑制中受益的疾病或病症的方法。(Described herein are compounds that inhibit transglutaminase 2(TG2) and pharmaceutical compositions comprising such compounds. Also described herein are methods of using such TG2 inhibitors, alone or in combination with other compounds, to treat diseases or disorders that benefit from TG2 inhibition.)

1. A compound according to formula (I) or a pharmaceutically acceptable salt thereof:

wherein:

is a 9-membered bicyclic heteroaryl ring;

x, Y and Z are selected from ═ C (R)¹¹) -and-N-wherein at least two of X, Y and Z are ═ C (R)¹¹)-；

R¹And R²Independently selected from H and optionally substituted alkyl; or R¹And R²Together with the nitrogen to which they are attached form an optionally substituted 3-, 4-, 5-, or 6-membered heterocycloalkyl ring;

R³is-N (H) C (O) OR⁵、-OC(O)NR⁶R⁷、-N(H)C(O)NR⁶R⁷or-N (H) C (O) R⁸；

Each R⁴Independently selected from halogen, -CN、-OR⁹、-SR⁹、-N(R¹⁰)₂、-S(O)R⁹、-S(O)₂R⁹、-NHS(O)₂R⁹、-S(O)₂N(R¹⁰)₂、-C(O)R⁹、-C(O)OR⁹、-OC(O)R⁹、-C(O)N(R¹⁰)₂、-OC(O)N(R¹⁰)₂、-NR¹⁰C(O)N(R¹⁰)₂、-NR¹⁰C(O)R⁹、-NR¹⁰C(O)OR⁹Optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted phenyl and optionally substituted heteroaryl;

R⁵Selected from the group consisting of optionally substituted alkyl, optionally substituted heterocycloalkyl, optionally substituted phenyl, and optionally substituted heteroaryl;

R⁶and R⁷Independently selected from H and optionally substituted alkyl; or R⁶And R⁷Together with the nitrogen to which they are attached form an optionally substituted 5-or 6-membered heterocycloalkyl ring;

R⁸selected from optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted phenyl, optionally substituted heterocycloalkyl, and optionally substituted heteroaryl;

each R⁹Independently selected from optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted phenyl and optionally substituted heteroaryl;

each R¹⁰Independently selected from the group consisting of H, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted phenyl, and optionally substituted heteroaryl;

each R¹¹Independently selected from H, halogen and optionally substituted alkyl;

n is 0, 1, 2, 3 or 4; and

p is 0, 1 or 2.

2. A compound according to formula (II):

wherein:

is a 9-membered bicyclic heteroaryl ring;

x, Y and Z are selected from ═ C (R)¹¹) -and-N-wherein at least two of X, Y and Z are ═ C (R)¹¹)-；

R¹And R²Independently selected from H, C_1-6Alkyl and-C_1-6alkyl-OH; or R¹And R²Together with the nitrogen to which they are attached form a 3-, 4-, 5-or 6-membered heterocycloalkyl ring, optionally substituted with one or two substituents independently selected from halogen and C _1-6A group of alkyl groups;

R³selected from-N (H) C (O) OR⁵、-OC(O)NR⁶R⁷、-N(H)C(O)NR⁶R⁷and-N (H) C (O) R⁸；

Each R⁴Independently selected from halogen, -CN, -OR⁹、-SR⁹、-N(R¹⁰)₂、-S(O)R⁹、-S(O)₂R⁹、-NHS(O)₂R⁹、-S(O)₂N(R¹⁰)₂、-C(O)R⁹、-C(O)OR⁹、-OC(O)R⁹、-C(O)N(R¹⁰)₂、-OC(O)N(R¹⁰)₂、-NR¹⁰C(O)N(R¹⁰)₂、-NR¹⁰C(O)R⁹、-NR¹⁰C(O)OR⁹、C_1-10Alkyl radical, C_1-10alkyl-OH, C_1-10alkyl-OR⁹、C_2-10Alkenyl radical, C_2-10Alkynyl, C_1-10Haloalkyl, C_1-10haloalkyl-OH, C_2-10Haloalkenyl, C_3-12Cycloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl, -C_2-6alkenyl-C_3-12Cycloalkyl, phenyl, -C_1-6Alkyl-phenyl, -C_2-6Alkenyl-phenyl, C_2-9Heterocycloalkyl and C_2-9Heteroaryl, in which phenyl, -C_1-6Alkyl-phenyl, -C_2-6Alkenyl-phenyl, C_2-9Heterocycloalkyl and C_2-9Heteroaryl is optionally substituted with one, two or three independently selected from halogen and C_1-6A group of alkyl groups;

R⁵is selected from C_1-6Alkyl, -C_1-6alkyl-OH, -C_1-6alkyl-O-C_1-6Alkyl, -C_1-6alkyl-O-C (O) C_1-6Alkyl radical, C_2-9Heterocycloalkyl, -C_1-6alkyl-C_2-9Heterocycloalkyl, phenyl, -C_1-6Alkyl-phenyl and C_2-9Heteroaryl group, wherein C_2-9Heterocycloalkyl, -C_1-6alkyl-C_2-9Heterocycloalkyl, phenyl, -C_1-6Alkyl-phenyl and C_2-9Heteroaryl is optionally substituted with one or two substituents independently selected from halogen and C_1-6A group of alkyl groups;

R⁶and R⁷Independently selected from H, C_1-6Alkyl, -C_1-6alkyl-OH, -C_1-6alkyl-O-C_1-6Alkyl and-C_1-6alkyl-N (C)_1-6Alkyl radical)₂(ii) a Or R⁶And R⁷Together with the nitrogen to which they are attached form a 5-or 6-membered heterocycloalkyl ring, optionally substituted with one or two substituents independently selected from halogen and C _1-6A group of alkyl groups;

R⁸is selected from C_1-6Alkyl radical, C_1-6Haloalkyl, -C_1-6alkyl-OH, -C_1-6alkyl-O-C_1-6Alkyl radical, C_3-6Cycloalkyl, phenyl, C_2-9Heterocycloalkyl and C_2-9Heteroaryl group, wherein C_3-6Cycloalkyl, phenyl, C_2-9Heterocycloalkyl and C_2-9Heteroaryl is optionally substituted with one or two substituents independently selected from halogen and C_1-6A group of alkyl groups;

each R⁹Independently selected from C_1-10Alkyl radical, C_1-10Haloalkyl, C_3-12Cycloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl, phenyl, -C_1-6Alkyl-phenyl and C_2-9Heteroaryl, in which phenyl, -C_1-6Alkyl-phenyl and C_2-9Heteroaryl is optionalSubstituted with one or two independently selected from halogen and C_1-6A group of alkyl groups;

each R¹⁰Independently selected from H, C_1-10Alkyl radical, C_1-10Haloalkyl, C_3-12Cycloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl, phenyl, -C_1-6Alkyl-phenyl and C_2-9Heteroaryl, in which phenyl, -C_1-6Alkyl-phenyl and C_2-9Heteroaryl is optionally substituted with one or two substituents independently selected from halogen and C_1-6A group of alkyl groups;

each R¹¹Independently selected from H, halogen, C_1-6Alkyl and C_1-6A haloalkyl group;

n is 0, 1, 2, 3 or 4; and

p is 0, 1 or 2.

3. A compound according to claim 1 or 2, or a pharmaceutically acceptable salt thereof,

wherein X, Y and Z are each ═ C (R)¹¹)-。

4. A compound according to claim 3 or a pharmaceutically acceptable salt thereof,

Wherein X and Y are each ═ c (h) -; and Z is ═ C (CH) -, (CH)₃) -or ═ c (cl) -.

5. A compound according to claim 4 or a pharmaceutically acceptable salt thereof,

wherein X, Y and Z are each ═ C (H) -.

6. A compound according to any one of claims 1 to 5, or a pharmaceutically acceptable salt thereof,

whereinSelected from: benzimidazolyl, imidazopyridinyl, purinyl, indolyl, pyrrolopyridinyl, pyrrolopyrimidinyl, benzoxazolyl, benzothiazolyl, imidazopyrazinyl, imidazopyridazinyl, pyrrolopyrazinylAzinyl, pyrrolopyridazinyl, oxazolopyridyl, oxazolopyrimidinyl, oxazolopyridazinyl, benzofuranyl, furopyridinyl, furopyrimidinyl, furopyrazinyl, furopyridazinyl, thiazolopyridyl, thiazolopyrimidinyl, thiazolopyridazinyl, benzothiophenyl, thienopyridinyl, thienopyrimidinyl, thienopyrazinyl, thienopyridazinyl, indolizinyl, pyrrolotriazinyl, imidazotriazinyl, triazolopyridinyl, triazolopyridazinyl, triazolopyrimidinyl and triazolopyrazinyl groups.

7. A compound according to claim 6 or a pharmaceutically acceptable salt thereof,

WhereinSelected from: benzimidazolyl, imidazopyridinyl, purinyl, indolyl, pyrrolopyridinyl, pyrrolopyrimidinyl, benzoxazolyl, and benzothiazolyl.

8. A compound according to claim 7 or a pharmaceutically acceptable salt thereof,

whereinIs selected from

9. The compound according to claim 8 or a pharmaceutically acceptable salt thereof,

wherein R is⁴Independently selected from halogen and optionally substituted alkyl.

10. A compound according to claim 9 or a pharmaceutically acceptable salt thereof,

wherein R is⁴Independently selected from the group consisting of chloro, fluoro, methyl, ethyl, butyl and isobutyl.

11. A compound according to any one of claims 1 to 10, or a pharmaceutically acceptable salt thereof, wherein R¹And R²Each is C_1-6An alkyl group.

12. The compound according to claim 11 or a pharmaceutically acceptable salt thereof,

wherein R is¹And R²Each is-CH₃。

13. The compound according to any one of claims 1-12, or a pharmaceutically acceptable salt thereof, wherein R³Selected from-N (H) C (O) OR⁵and-OC (O) NR⁶R⁷；R⁵Is C_1-6An alkyl group; and R is⁶And R⁷Independently selected from H and C_1-6An alkyl group.

14. A compound according to claim 1 or a pharmaceutically acceptable salt thereof,

wherein:

is benzimidazolyl, imidazopyridinyl, purinyl, indolyl, pyrrolopyridinyl, pyrrolopyrimidinyl, benzoxazolyl, benzothiazolyl, imidazopyrazinyl, imidazopyridazinyl, pyrrolopyrazinyl, pyrrolopyridazinyl, oxazolopyridyl, oxazolopyrimidinyl, oxazolopyridazinyl, benzofuranyl, furopyridinyl, furopyrimidinyl, furopyrazinyl, furopyridazinyl, thiazolopyridyl, thiazolopyrimidinyl, thiazolopyridazinyl, benzothienyl, thienopyridinyl, thienopyrimidinyl, thienopyrazinyl, thienopyridazinyl, indolizinyl, pyrrolotriazinyl, imidazotriazinyl, triazolopyridinyl, triazolopyridazinyl, triazolopyrimidinyl, triazolopyrazinyl, triazolopyrimidinyl or triazolopyrazinyl;

X, Y and Z is ═ C (R)¹¹)-；

R¹And R²Independently selected from H and C_1-6An alkyl group;

R³selected from-N (H) C (O) OR⁵and-OC (O) NR⁶R⁷；

Each R⁴Independently selected from halogen and C_1-10An alkyl group;

R⁵is C_1-6An alkyl group;

R⁶and R⁷Independently selected from H and C_1-6An alkyl group;

each R¹¹Independently selected from H, halogen and C_1-6An alkyl group;

n is 0, 1, 2, 3 or 4; and

p is 0, 1 or 2.

15. A compound according to claim 1 or a pharmaceutically acceptable salt thereof,

wherein:

is benzimidazolyl, imidazopyridinyl, purinyl, indolyl, pyrrolopyridinyl, pyrrolopyrimidinyl, benzoxazolyl or benzothiazolyl;

x, Y and Z is ═ C (R)¹¹)-；

R¹And R²Independently selected from H and C_1-6An alkyl group;

R³selected from-N (H) C (O) OR⁵and-OC (O) NR⁶R⁷；

Each R⁴Independently selected from halogen and C_1-10An alkyl group;

R⁵is C_1-6An alkyl group;

R⁶and R⁷Independently selected from H and C_1-6An alkyl group;

each R¹¹Independently selected from H, halogen and C_1-6An alkyl group;

n is 1, 2 or 3; and

p is 1.

16. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, which is:

2- [ [3- [ [ (E,2S) -7- (dimethylamino) -2- (methoxycarbonylamino) -7-oxo-hept-5-enoyl ] amino ] -2-oxo-1-pyridinyl ] methyl ] -4-isobutyl-benzimidazole-1-carboxylic acid tert-butyl ester;

methyl N- [ (E,1S) -6- (dimethylamino) -1- [ [1- [ (4-isobutyl-1H-benzimidazol-2-yl) methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] carbamate;

(S, E) -2- ((3- (7-amino-2- (((benzyloxy) carbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -4-isobutyl-1H-benzo [ d ] imidazole-1-carboxylic acid tert-butyl ester;

(S, E) - (7-amino-1- ((1- ((4-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid benzyl ester;

(S, E) -2- ((3- (7-amino-2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -4-isobutyl-1H-benzo [ d ] imidazole-1-carboxylic acid tert-butyl ester;

(S, E) - (7-amino-1- ((1- ((4-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -2- ((3- (2- (((benzyloxy) carbonyl) amino) -7- (dimethylamino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -4-isobutyl-1H-benzo [ d ] imidazole-1-carboxylic acid tert-butyl ester;

(S, E) - (7- (dimethylamino) -benzyl 1- ((1- ((4-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamate;

2- ((3- ((2S, E) -7-amino-7-oxo-2- (((((tetrahydrofuran-3-yl) oxy) carbonyl) amino) hept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -4-isobutyl-1H-benzo [ d ] imidazole-1-carboxylic acid tert-butyl ester;

((S, E) -7- (dimethylamino) -1- ((1- ((4-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid (tetrahydrofuran-3-yl) methyl ester;

((S, E) -7-amino-1- ((1- ((4-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid tetrahydrofuran-3-yl ester;

2- ((3- ((2S, E) -7-amino-7-oxo-2- (((((tetrahydrofuran-3-yl) methoxy) carbonyl) amino) hept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -4-isobutyl-1H-benzo [ d ] imidazole-1-carboxylic acid tert-butyl ester;

((S, E) -7-amino-1- ((1- ((4-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid (tetrahydrofuran-3-yl) methyl ester;

(S, E) - (7- (dimethylamino) -2-hydroxyethyl 1- ((1- ((4-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamate;

(S, E) -4-isobutyl-2- ((3- (2- ((methoxycarbonyl) amino) -7- (methylamino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -1H-benzo [ d ] imidazole-1-carboxylic acid tert-butyl ester;

(S, E) - (1- ((1- ((4-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (methylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -2- ((3- (7- (dimethylamino) -2- ((dimethylcarbamoyl) oxy) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -4-isobutyl-1H-benzo [ d ] imidazole-1-carboxylic acid tert-butyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((7-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -1- ((1- ((5, 6-difluoro-7-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) -tert-butyl 2- ((3- (7- (dimethylamino) -2- ((dimethylcarbamoyl) oxy) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5, 6-difluoro-4-isobutyl-1H-benzo [ d ] imidazole-1-carboxylate;

(S, E) - (1- ((1- ((5, 6-difluoro-7-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -tert-butyl 2- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5, 6-difluoro-4-isobutyl-1H-benzo [ d ] imidazole-1-carboxylate;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((5-fluoro-7-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) -tert-butyl 2- ((3- (7- (dimethylamino) -2- ((dimethylcarbamoyl) oxy) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -6-fluoro-4-isobutyl-1H-benzo [ d ] imidazole-1-carboxylate;

(S, E) - (7- (dimethylamino) -1- ((1- ((6-fluoro-4-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -6- (3, 3-dimethylureido) -N7- (1- ((5-fluoro-7-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -N1, N1-dimethylhept-2-enediamide;

(S, E) -tert-butyl 2- ((3- (7- (dimethylamino) -2- (3, 3-dimethylureido) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -6-fluoro-4-isobutyl-1H-benzo [ d ] imidazole-1-carboxylate;

(R, E) - (7- (dimethylamino) -1- ((1- ((4-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -2- ((3- (7- (dimethylamino) -2- (3, 3-dimethylureido) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -4-isobutyl-1H-benzo [ d ] imidazole-1-carboxylic acid tert-butyl ester;

(S, E) -6- (3, 3-dimethylureido) -N7- (1- ((4-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -N1, N1-dimethylhept-2-enediamide;

(S, E) -tert-butyl 2- ((3- (7- (dimethylamino) -2- (3- (2-methoxyethyl) -3-methylureido) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -6-fluoro-4-isobutyl-1H-benzo [ d ] imidazole-1-carboxylate;

(S, E) -N7- (1- ((5-fluoro-7-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -6- (3- (2-methoxyethyl) -3-methylureido) -N1, N1-dimethylhept-2-enediamide;

(S, E) -tert-butyl 2- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -4-isobutyl-1H-imidazo [4,5-c ] pyridine-1-carboxylate;

(S, E) -tert-butyl 2- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -7-isobutyl-3H-imidazo [4,5-b ] pyridine-3-carboxylate;

(S, E) - (7- (dimethylamino) -1- ((1- ((7-isobutyl-3H-imidazo [4,5-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((4-isobutyl-1H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((6-isobutyl-2-methyl-9H-purin-8-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -8- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -6-isobutyl-2-methyl-9H-purine-9-carboxylic acid tert-butyl ester;

(S, E) - (1- ((1- ((6- (2-cyclopropylethyl) -9H-purin-8-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1, 7-dioxo-1- ((2-oxo-1- ((6-pentyl-9H-purin-8-yl) methyl) -1, 2-dihydropyridin-3-yl) amino) hept-5-en-2-yl) carbamic acid methyl ester;

n- [ (E,1S) -6- (dimethylamino) -1- [ [1- [ [6- (2-methylprop-1-enyl) -9H-purin-8-yl ] methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((6-isobutyl-9H-purin-8-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((6- (2-methylprop-1-en-1-yl) -9H-purin-8-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((6-isobutyl-9H-purin-8-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((7- (2-methylprop-1-en-1-yl) -3H-imidazo [4,5-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((4- (2-methylprop-1-en-1-yl) -1H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (1- ((1- ((6-cyclohexyl-9H-purin-8-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -1- ((1- ((6-cyclohexyl-9H-purin-8-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((7-fluoro-4-isobutyl-1H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((2-methyl-6- (2-methylprop-1-en-1-yl) -9H-purin-8-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((7- (2-methylprop-1-en-1-yl) -3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

Dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((7-fluoro-4-isobutyl-1H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((7-fluoro-4- (2-methylprop-1-en-1-yl) -1H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

((S, E) -7- (dimethylamino) -1, 7-dioxo-1- ((2-oxo-1- ((6- ((E) -styryl) -9H-purin-8-yl) methyl) -1, 2-dihydropyridin-3-yl) amino) hept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((7-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((4-isobutyl-6-methyl-1H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((6-methyl-4- (2-methylprop-1-en-1-yl) -1H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1, 7-dioxo-1- ((2-oxo-1- ((6-phenethyl-7H-purin-8-yl) methyl) -1, 2-dihydropyridin-3-yl) amino) hept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1, 7-dioxo-1- ((2-oxo-1- ((6-phenethyl-9H-purin-8-yl) methyl) -1, 2-dihydropyridin-3-yl) amino) hept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((7- (2-methylprop-1-en-1-yl) -3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((7-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

methyl (S, E) -1- ((1- ((6- ((E) -2-cyclopropylvinyl) -9H-purin-8-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamate;

2- [ [3- [ [ (E,2S) -7- (dimethylamino) -2- (methoxycarbonylamino) -7-oxo-hept-5-enoyl ] amino ] -2-oxo-1-pyridinyl ] methyl ] -5, 7-difluoro-4-isobutyl-benzimidazole-1-carboxylic acid tert-butyl ester;

Methyl N- [ (E,1S) -1- [ [1- [ (5, 7-difluoro-4-isobutyl-1H-benzimidazol-2-yl) methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6- (dimethylamino) -6-oxo-hex-4-enyl ] carbamate;

(S, E) -tert-butyl 2- ((3- (2- ((tert-butoxycarbonyl) amino) -7- (dimethylamino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -4-isobutyl-1H-benzo [ d ] imidazole-1-carboxylate;

(S, E) -N7- (1- ((4-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -N1, N1-dimethyl-6- (oxazole-5-carboxamido) hept-2-enediamide;

(S, E) -N7- (1- ((4-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -N1, N1-dimethyl-6- (pyrimidine-2-carboxamido) hept-2-enediamide;

(S, E) -6- (2-fluorobenzamido) -N7- (1- ((4-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -N1, N1-dimethylhept-2-enediamide;

(S, E) -N7- (1- ((4-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -N1, N1-dimethyl-6- (oxazole-2-carboxamido) hept-2-enediamide;

(S, E) -N7- (1- ((4-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -N1, N1-dimethyl-6- (1-methyl-1H-imidazole-5-carboxamido) hept-2-enediamide;

(S, E) -N7- (1- ((4-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -N1, N1-dimethyl-6- (1-methyl-1H-imidazole-2-carboxamido) hept-2-enediamide;

(S, E) -N7- (1- ((4-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -N1, N1-dimethyl-6- (pyridin-2-ylcarboxamido) hept-2-enediamide;

(S, E) -N7- (1- ((4-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -6- (3-methoxypropionylamino) -N1, N1-dimethylhept-2-enediamide;

(S, E) -N7- (1- ((7-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -6- (2-methoxyacetylamino) -N1, N1-dimethylhept-2-enediamide;

(6S, E) -N7- (1- ((7-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -N1, N1-dimethyl-6- (tetrahydrofuran-2-carboxamido) hept-2-enediamide;

(S, E) -2- ((3- (7-amino-2- (((2-methoxyethoxy) carbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -1H-benzo [ d ] imidazole-1-carboxylic acid tert-butyl ester;

(S, E) - (1- ((1- ((1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7-amino-1, 7-dioxohept-5-en-2-yl) carbamic acid 2-methoxyethyl ester;

(S, E) - (1- ((1- ((1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7-amino-1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (1- ((1- ((1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (benzyl 1- ((1- ((1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamate;

(S, E) -tert-butyl 2- ((3- (2- ((tert-butoxycarbonyl) amino) -7- (dimethylamino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -1H-benzo [ d ] imidazole-1-carboxylate;

(S, E) -tert-butyl 2- ((3- (2- ((methoxycarbonyl) amino) -7- (methylamino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -1H-benzo [ d ] imidazole-1-carboxylate;

(S, E) - (1- ((1- ((1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (methylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((5-fluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

Dimethylcarbamic acid (S, E) -1- ((1- ((5, 6-difluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) -tert-butyl 2- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5, 6-difluoro-1H-benzo [ d ] imidazole-1-carboxylate;

(S, E) - (1- ((1- ((5, 6-difluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (R, E) -7- (dimethylamino) -1- ((1- ((5-fluoro-1H-benzo [ d)]Imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl-3, 3-d₂An ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((5-fluoro-1H-benzo [ d)]Imidazol-2-yl) methyl) -2-oxo-1, 2-dihydroPyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl-3, 3-d₂An ester;

(S, E) - (1- ((1- ((1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7-amino-1, 7-dioxohept-5-en-2-yl) carbamic acid 2-hydroxyethyl ester;

(S) -2- ((((S, E) -1- ((1- ((1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7-amino-1, 7-dioxohept-5-en-2-yl) carbamoyl) oxy) ethyl 2- ((S) -2-amino-3-methylbutanoate) -3-methylbutanoate;

(S, E) -N7- (1- ((1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -6- (2-hydroxyacetamido) -N1, N1-dimethylhept-2-enediamide;

(E,6S) -N' - [1- (1H-benzoimidazol-2-ylmethyl) -2-oxo-3-pyridinyl ] -6- (3-hydroxypropionylamino) -N, N-dimethyl-hept-2-enediamide;

(S, E) -N7- (1- ((1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -6- (4-hydroxybutyrylamino) -N1, N1-dimethylhept-2-enediamide;

(S, E) - (1- ((1- ((1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- ((2-hydroxyethyl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((6-fluoro-4-neopentyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (1- ((1- ((6-fluoro-4-neopentyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxo-7- (pyrrolidin-1-yl) hept-5-en-2-yl) carbamic acid methyl ester;

Dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((5-fluoro-7-neopentyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -2-methoxyethyl 1- ((1- ((6-fluoro-4-neopentyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamate;

(2-methoxyethyl) (methyl) carbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((5-fluoro-7-neopentyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -1- ((1- ((5-fluoro-7-neopentyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxo-7- (pyrrolidin-1-yl) hept-5-en-2-yl ester;

(S, E) -tert-butyl 2- ((3- (7- (dimethylamino) -2- ((dimethylcarbamoyl) oxy) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -6-methoxy-4-neopentyl-1H-benzo [ d ] imidazole-1-carboxylate;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((6-methoxy-4-neopentyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) -2- ((3- (7-amino-2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -4-neopentyl-1H-benzo [ d ] imidazole-1-carboxylic acid tert-butyl ester;

(S, E) -2- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -4-neopentyl-1H-benzo [ d ] imidazole-1-carboxylic acid tert-butyl ester;

(S, E) - (7-amino-1- ((1- ((7-neopentyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((7-neopentyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -tert-butyl 2- ((3- (7- (dimethylamino) -7-oxo-2- ((((tetrahydro-2H-pyran-4-yl) methoxy) carbonyl) amino) hept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -4-neopentyl-1H-benzo [ d ] imidazole-1-carboxylate;

(S, E) - (7- (dimethylamino) -1- ((1- ((7-neopentyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid (tetrahydro-2H-pyran-4-yl) methyl ester;

((S, E) -7- (dimethylamino) -1- ((1- ((4-neopentyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid tetrahydrofuran-3-yl ester;

2- ((3- ((2S, E) -7-amino-7-oxo-2- (((((tetrahydrofuran-3-yl) oxy) carbonyl) amino) hept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -4-neopentyl-1H-benzo [ d ] imidazole-1-carboxylic acid tert-butyl ester;

((S, E) -7-amino-1- ((1- ((4-neopentyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid tetrahydrofuran-3-yl ester;

(S, E) -tert-butyl 2- ((3- (7-amino-7-oxo-2- ((((tetrahydro-2H-pyran-4-yl) methoxy) carbonyl) amino) hept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -4-neopentyl-1H-benzo [ d ] imidazole-1-carboxylate;

(S, E) - (7-amino-1- ((1- ((4-neopentyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid (tetrahydro-2H-pyran-4-yl) methyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((7-fluoro-4-neopentyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) -tert-butyl 2- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5, 7-difluoro-4-neopentyl-1H-benzo [ d ] imidazole-1-carboxylate;

(S, E) - (1- ((1- ((5, 7-difluoro-4-neopentyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

n, N-dimethylcarbamic acid [ (E,1S) -6- (dimethylamino) -1- [ [1- [ [4- (2, 2-dimethylpropyl) -6-fluoro-1-methyl-benzimidazol-2-yl ] methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] ester;

(S, E) - (7- (dimethylamino) -2-methoxyethyl 1- ((1- ((6-fluoro-1-methyl-4-neopentyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamate;

2- [ [5- [ [ (E,2S) -7- (dimethylamino) -2- (dimethylcarbamoyloxy) -7-oxo-hept-5-enoyl ] amino ] -6-oxo-pyridazin-1-yl ] methyl ] -4- (2, 2-dimethylpropyl) -6-fluoro-benzimidazole-1-carboxylic acid tert-butyl ester;

n, N-dimethylcarbamic acid [ (E,1S) -6- (dimethylamino) -1- [ [2- [ [7- (2, 2-dimethylpropyl) -5-fluoro-1H-benzimidazol-2-yl ] methyl ] -3-oxo-pyridazin-4-yl ] carbamoyl ] -6-oxo-hex-4-enyl ] ester TFA salt;

(S, E) -tert-butyl 2- ((3- (7- (dimethylamino) -2- ((dimethylcarbamoyl) oxy) -7-oxohept-5-enoylamino) -2-oxopyrazin-1 (2H) -yl) methyl) -6-fluoro-4-neopentyl-1H-benzo [ d ] imidazole-1-carboxylate;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((5-fluoro-7-neopentyl-1H-benzo [ d ] imidazol-2-yl) methyl) -6-oxo-1, 6-dihydropyrimidin-5-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

2- [ [3- [ [ (E,2S) -7- (dimethylamino) -2- (methoxycarbonylamino) -7-oxo-hept-5-enoyl ] amino ] -2-oxo-1-pyridinyl ] methyl ] -6-fluoro-4- (3,3, 3-trifluoropropyl) benzimidazole-1-carboxylic acid tert-butyl ester;

methyl N- [ (E,1S) -6- (dimethylamino) -1- [ [1- [ [ 5-fluoro-7- (3,3, 3-trifluoropropyl) -1H-benzimidazol-2-yl ] methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] carbamate;

(S, E) - (7-amino-1, 7-dioxo-1- ((2-oxo-1- ((4- (3,3, 3-trifluoropropyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -1, 2-dihydropyridin-3-yl) amino) hept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1, 7-dioxo-1- ((2-oxo-1- ((4- (3,3, 3-trifluoropropyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -1, 2-dihydropyridin-3-yl) amino) hept-5-en-2-yl) carbamic acid methyl ester;

Dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((5-fluoro-7- (3,3, 3-trifluoropropyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) -6-fluoro-2- ((3- (2- ((methoxycarbonyl) amino) -7-oxo-7- (pyrrolidin-1-yl) hept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -4- (3,3, 3-trifluoropropyl) -1H-benzo [ d ] imidazole-1-carboxylic acid tert-butyl ester;

(S, E) - (1- ((1- ((6-fluoro-4- (3,3, 3-trifluoropropyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxo-7- (pyrrolidin-1-yl) hept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -tert-butyl 2- ((3- (2- ((dimethylcarbamoyl) oxy) -7- (methylamino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5-fluoro-7- (3,3, 3-trifluoropropyl) -1H-benzo [ d ] imidazole-1-carboxylate;

dimethylcarbamic acid (S, E) -1- ((1- ((5-fluoro-7- (3,3, 3-trifluoropropyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (methylamino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (1- ((1- ((4, 6-difluoro-7- (3,3, 3-trifluoropropyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -2- ((3- (7- (dimethylamino) -2- ((dimethylcarbamoyl) oxy) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5, 7-difluoro-4- (3,3, 3-trifluoropropyl) -1H-benzo [ d ] imidazole-1-carboxylic acid tert-butyl ester;

dimethylcarbamic acid (S, E) -1- ((1- ((4, 6-difluoro-7- (3,3, 3-trifluoropropyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) -tert-butyl 2- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5, 6-difluoro-4- (3,3, 3-trifluoropropyl) -1H-benzo [ d ] imidazole-1-carboxylate;

(S, E) - (1- ((1- ((5, 6-difluoro-4- (3,3, 3-trifluoropropyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

n, N-dimethylcarbamic acid [ (E,1S) -6- (dimethylamino) -1- [ [1- [ [ 6-fluoro-1-methyl-4- (3,3, 3-trifluoropropyl) benzimidazol-2-yl ] methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] ester;

(S, E) - (7- (dimethylamino) -2-methoxyethyl 1- ((1- ((6-fluoro-1-methyl-4- (3,3, 3-trifluoropropyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamate;

2- [ [5- [ [ (E,2S) -7- (dimethylamino) -2- (methoxycarbonylamino) -7-oxo-hept-5-enoyl ] amino ] -6-oxo-pyrimidin-1-yl ] methyl ] -6-fluoro-4- (3,3, 3-trifluoropropyl) benzimidazole-1-carboxylic acid tert-butyl ester;

methyl N- [ (E,1S) -6- (dimethylamino) -1- [ [1- [ [ 5-fluoro-7- (3,3, 3-trifluoropropyl) -1H-benzimidazol-2-yl ] methyl ] -6-oxo-pyrimidin-5-yl ] carbamoyl ] -6-oxo-hex-4-enyl ] carbamate;

(S, E) - (1- ((1- ((5-fluoro-7- (3,3, 3-trifluoropropyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -6-oxo-1, 6-dihydropyrimidin-5-yl) amino) -7- (methylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -6-fluoro-2- ((5- (2- ((methoxycarbonyl) amino) -7- (methylamino) -7-oxohept-5-enoylamino) -6-oxopyrimidin-1 (6H) -yl) methyl) -4- (3,3, 3-trifluoropropyl) -1H-benzo [ d ] imidazole-1-carboxylic acid tert-butyl ester;

4- (cyclopropylmethyl) -2- [ [3- [ [ (E,2S) -7- (dimethylamino) -2- (methoxycarbonylamino) -7-oxo-hept-5-enoyl ] amino ] -2-oxo-1-pyridinyl ] methyl ] -6-fluoro-benzimidazole-1-carboxylic acid tert-butyl ester;

methyl N- [ (E,1S) -1- [ [1- [ [4- (cyclopropylmethyl) -6-fluoro-1H-benzimidazol-2-yl ] methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6- (dimethylamino) -6-oxo-hex-4-enyl ] carbamate;

(S, E) -4- (cyclopropylmethyl) -2- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -1H-benzo [ d ] imidazole-1-carboxylic acid tert-butyl ester;

(S, E) - (1- ((1- ((4- (cyclopropylmethyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -2- ((3- (7-amino-2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -4- (cyclopropylmethyl) -1H-benzo [ d ] imidazole-1-carboxylic acid tert-butyl ester;

(S, E) - (7-amino-1- ((1- ((4- (cyclopropylmethyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (1- ((1- ((4- (2, 4-difluorophenoxy) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -2- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -4-phenoxy-1H-benzo [ d ] imidazole-1-carboxylic acid tert-butyl ester;

(S, E) - (7- (dimethylamino) -1, 7-dioxo-1- ((2-oxo-1- ((7-phenoxy-1H-benzo [ d ] imidazol-2-yl) methyl) -1, 2-dihydropyridin-3-yl) amino) hept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7-amino-1, 7-dioxo-1- ((2-oxo-1- ((4-phenoxy-1H-benzo [ d ] imidazol-2-yl) methyl) -1, 2-dihydropyridin-3-yl) amino) hept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (1- ((1- ((6- (2, 4-difluorophenoxy) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -methyl (1- ((1- ((7- ((2, 4-difluorobenzyl) oxy) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamate;

(S, E) - (7-amino-1- ((1- ((4-isopropoxy-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid benzyl ester;

(S, E) - (1- ((1- ((7- (benzyloxy) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -benzyl 1- ((1- ((7-isobutoxy-1-methyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamate;

(S, E) - (7-amino-1- ((1- ((7-isobutoxy-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7-amino-1- ((1- ((7- (benzyloxy) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7-amino-1- ((1- ((4-isopropoxy-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7-amino-1- ((1- ((7- (cyclopropylmethoxy) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (1- ((1- ((6- ((2, 4-difluorobenzyl) oxy) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (1- ((1- ((4- (2, 2-difluoroethoxy) -6-fluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7-amino-1- ((1- ((4- (2, 2-difluoroethoxy) -6-fluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((6-fluoro-4- (2,2, 2-trifluoroethoxy) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7-amino-1- ((1- ((6-fluoro-4- (2,2, 2-trifluoroethoxy) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (1- ((1- ((7- ((2, 4-difluorobenzyl) oxy) -5-fluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (1- ((1- ((4- ((2, 4-difluorobenzyl) oxy) -6-fluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (methylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7-amino-1- ((1- ((7- ((2, 4-difluorobenzyl) oxy) -5-fluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -1- ((1- ((7- ((2, 4-difluorobenzyl) oxy) -5-fluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

(2-methoxyethyl) (methyl) carbamic acid (S, E) -1- ((1- ((7- ((2, 4-difluorobenzyl) oxy) -5-fluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (1- ((1- ((7- (cyclopropylmethoxy) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethyl-amino) -1- ((1- ((5-fluoro-7- (1,1,2, 2-tetrafluoroethoxy) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -N7- (1- ((7- (2, 4-difluorophenoxy) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -N1, N1-dimethyl-6- (oxazole-2-carboxamido) hept-2-enediamide;

(S, E) -N7- (1- ((7- (2, 4-difluorophenoxy) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -6- (2-methoxyacetylamino) -N1, N1-dimethylhept-2-enediamide;

(S, E) -N7- (1- ((7- (2, 4-difluorophenoxy) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -N1, N1-dimethyl-6- (1-methyl-1H-imidazole-5-carboxamido) hept-2-enediamide;

(S, E) -N7- (1- ((4- ((2, 4-difluorobenzyl) oxy) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -N1, N1-dimethyl-6- (oxazole-2-carboxamido) hept-2-enediamide;

(S, E) -N7- (1- ((7- ((2, 4-difluorobenzyl) oxy) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -6- (2-methoxyacetylamino) -N1, N1-dimethylhept-2-enediamide;

(S, E) -N7- (1- ((4- ((2, 4-difluorobenzyl) oxy) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -N1, N1-dimethyl-6- (1-methyl-1H-imidazole-2-carboxamido) hept-2-enediamide;

(S, E) -N7- (1- ((7- ((2, 4-difluorobenzyl) oxy) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -6- (4, 4-difluorocyclohexane-1-carboxamido) -N1, N1-dimethylhept-2-enediamide;

(S, E) -N7- (1- ((7- ((2, 4-difluorobenzyl) oxy) -5-fluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -6- (2-methoxyacetylamino) hept-2-enediamide;

(S, E) -N7- (1- ((7- ((2, 4-difluorobenzyl) oxy) -5-fluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -6- (5-fluoropyridin-2-ylcarboxamido) hept-2-enediamide;

(S, E) -N7- (1- ((4- ((2, 4-difluorobenzyl) oxy) -6-fluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -6- (2-methoxyacetylamino) -N1, N1-dimethylhept-2-enediamide;

(S, E) -N7- (1- ((4- ((2, 4-difluorobenzyl) oxy) -6-fluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -6- (5-fluoropyridin-2-ylcarboxamido) -N1, N1-dimethylhept-2-enediamide;

methyl N- [ (E,1S) -1- [ [1- [ [4- [ (2, 4-difluorophenoxy) methyl ] -1H-benzimidazol-2-yl ] methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6- (dimethylamino) -6-oxo-hex-4-enyl ] carbamate;

(S, E) - (7- (dimethylamino) -1- ((1- ((4- (isopropoxymethyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -tert-butyl 2- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -4- (3,3, 3-trifluoro-2- (trifluoromethyl) propyl) -1H-benzo [ d ] imidazole-1-carboxylate;

(S, E) - (7- (dimethylamino) -1, 7-dioxo-1- ((2-oxo-1- ((4- (3,3, 3-trifluoro-2- (trifluoromethyl) propyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -1, 2-dihydropyridin-3-yl) amino) hept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7-amino-1, 7-dioxo-1- ((2-oxo-1- ((4- (3,3, 3-trifluoro-2- (trifluoromethyl) propyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -1, 2-dihydropyridin-3-yl) amino) hept-5-en-2-yl) carbamic acid methyl ester;

((2S, E) -7- (dimethylamino) -1- ((1- ((4- (1-hydroxy-2-methylpropyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

((2S, E) -7-amino-1- ((1- ((4- (1-hydroxy-2-methylpropyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

((2S, E) -7- (dimethylamino) -1- ((1- ((7- (1-hydroxy-2-methylpropyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

((2S, E) -7- (dimethylamino) -1- ((1- ((7- (1-fluoro-2-methylpropyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

((2S, E) -7- (dimethylamino) -1- ((1- ((7- (1-hydroxy-2, 2-dimethylpropyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

((2S, E) -7-amino-1- ((1- ((7- (1-hydroxy-2, 2-dimethylpropyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

tert-butyl (2S, E) -7- (dimethylamino) -1- ((1- ((7- (1-hydroxy-2, 2-dimethylpropyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamate;

(6S, E) -N7- (1- ((7- (1-hydroxy-2, 2-dimethylpropyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -N1, N1-dimethyl-6- (oxazole-2-carboxamido) hept-2-enediamide;

(S, E) - (7- (dimethylamino) -1, 7-dioxo-1- ((2-oxo-1- ((7-pivaloyl-1H-benzo [ d ] imidazol-2-yl) methyl) -1, 2-dihydropyridin-3-yl) amino) hept-5-en-2-yl) carbamic acid methyl ester;

((2S, E) -7- (dimethylamino) -1- ((1- ((7- (1-fluoro-2, 2-dimethylpropyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

((2S, E) -7-amino-1- ((1- ((4- (1-fluoro-2, 2-dimethylpropyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (1- ((1- ((4- (1, 1-difluoro-2-hydroxy-2-methylpropyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (1- ((1- ((4- (1, 1-difluoro-2-methylpropyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7-amino-1- ((1- ((4- (1, 1-difluoro-2-methylpropyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (1- ((1- ((4- (1, 1-difluoro-2-methylallyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7-amino-1- ((1- ((4- (1, 1-difluoro-2-methylallyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (1- ((1- ((7- (tert-butoxy) -5-fluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7-amino-1- ((1- ((7- (tert-butoxy) -5-fluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

n, N-dimethylcarbamic acid [ (E,1S) -6- (dimethylamino) -1- [ [1- [ (5-fluoro-1-methyl-benzimidazol-2-yl) methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] ester;

Methyl N- [ (E,1S) -6- (dimethylamino) -1- [ [1- [ (5-fluoro-1-methyl-benzimidazol-2-yl) methyl ] -6-oxo-pyrimidin-5-yl ] carbamoyl ] -6-oxo-hex-4-enyl ] carbamate;

dimethylcarbamic acid (S, E) -1- ((1- ((5, 6-difluoro-1-isopentyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -1- ((1- ((1- (cyclopropylmethyl) -5-fluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((5-fluoro-1-neopentyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((1-ethyl-5-fluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((5-fluoro-1-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

Dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((5-fluoro-1- (3,3, 3-trifluoropropyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -1- ((1- ((1- (2-cyclopropylethyl) -5, 6-difluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (1- ((1- ((1- (2-cyclopropylethyl) -5, 6-difluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -1- ((1- ((1- ((1-benzyl-5-fluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -6-oxo-1, 6-dihydropyrimidin-5-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -1- ((1- ((1- (2, 4-difluorobenzyl) -5-fluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -6-oxo-1, 6-dihydropyrimidin-5-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (1- ((1- ((1- (2, 4-difluorobenzyl) -5-fluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -6-oxo-1, 6-dihydropyrimidin-5-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

Dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((5-fluoro-1-neopentyl-1H-benzo [ d ] imidazol-2-yl) methyl) -6-oxo-1, 6-dihydropyrimidin-5-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (1- ((1- ((5, 6-difluoro-1- (2-isopropoxyethyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((5-fluoro-1- (4-fluorobenzyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -6-oxo-1, 6-dihydropyrimidin-5-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (1- ((1- ((1- (cyclopropylmethyl) -5-fluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -6-oxo-1, 6-dihydropyrimidin-5-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((5-fluoro-1-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -6-oxo-1, 6-dihydropyrimidin-5-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((1-ethyl-5-fluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -6-oxo-1, 6-dihydropyrimidin-5-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

Dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((5-fluoro-1-methyl-1H-benzo [ d ] imidazol-2-yl) methyl) -6-oxo-1, 6-dihydropyrimidin-5-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

2- [ [3- [ [ (E,2S) -7- (dimethylamino) -2- (dimethylcarbamoyloxy) -7-oxo-hept-5-enoyl ] amino ] -2-oxo-1-pyridinyl ] methyl ] -5-fluoro-benzimidazole-1-carboxylic acid ethyl ester;

2- [ [3- [ [ (E,2S) -7- (dimethylamino) -2- (dimethylcarbamoyloxy) -7-oxo-hept-5-enoyl ] amino ] -2-oxo-1-pyridinyl ] methyl ] -5-fluoro-benzimidazole-1-carboxylic acid cyclopropylmethyl ester;

(S, E) -methyl 2- ((3- (7- (dimethylamino) -2- ((dimethylcarbamoyl) oxy) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5-fluoro-1H-benzo [ d ] imidazole-1-carboxylate;

(S, E) -ethyl 2- ((3- (7- (dimethylamino) -2- ((dimethylcarbamoyl) oxy) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5, 6-difluoro-1H-benzo [ d ] imidazole-1-carboxylate;

(S, E) -2- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5, 6-difluoro-1H-benzo [ d ] imidazole-1-carboxylic acid cyclopropylmethyl ester;

(S, E) -ethyl 2- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5, 6-difluoro-1H-benzo [ d ] imidazole-1-carboxylate;

(S, E) -2- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5-fluoro-1H-benzo [ d ] imidazole-1-carboxylic acid cyclopropylmethyl ester;

(S, E) -ethyl 2- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5-fluoro-1H-benzo [ d ] imidazole-1-carboxylate;

2- [ [5- [ [ (E,2S) -7- (dimethylamino) -2- (methoxycarbonylamino) -7-oxo-hept-5-enoyl ] amino ] -6-oxo-pyrimidin-1-yl ] methyl ] -5-fluoro-benzimidazole-1-carboxylic acid methyl ester;

n, N-dimethylcarbamic acid [ (E,1S) -1- [ [1- [ (1-benzyl-6-fluoro-benzimidazol-2-yl) methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6- (dimethylamino) -6-oxo-hex-4-enyl ] ester;

n, N-dimethylcarbamic acid [ (E,1S) -1- [ [1- [ (1-benzyl-5-fluoro-benzimidazol-2-yl) methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6- (dimethylamino) -6-oxo-hex-4-enyl ] ester;

dimethylcarbamic acid (S, E) -1- ((1- ((1- (2, 4-difluorobenzyl) -5-fluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

Dimethylcarbamic acid (S, E) -1- ((1- ((1- (2, 4-difluorobenzyl) -6-fluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((5-fluoro-1- (4-fluorobenzyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((6-fluoro-1- (4-fluorobenzyl) -1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((5-fluoro-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -5-fluoro-2- ((3- (2- ((methoxycarbonyl) amino) -7-oxo-7- (pyrrolidin-1-yl) hept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -1H-indole-1-carboxylic acid tert-butyl ester;

(S, E) -5-fluoro-2- ((3- (2- (((2-hydroxyethoxy) carbonyl) amino) -7-oxo-7- (pyrrolidin-1-yl) hept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -1H-indole-1-carboxylic acid tert-butyl ester;

(S, E) - (1- ((1- ((5-fluoro-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxo-7- (pyrrolidin-1-yl) hept-5-en-2-yl) carbamic acid 2-hydroxyethyl ester;

(S, E) - (7-amino-1- ((1- ((5-fluoro-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (1- ((1- ((5-fluoro-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxo-7- (pyrrolidin-1-yl) hept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((5-fluoro-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(2-methoxyethyl) (methyl) carbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((5-fluoro-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

pyrrolidine-1-carboxylic acid (S, E) -7- (dimethylamino) -1- ((1- ((5-fluoro-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) -2- ((3- (7-amino-2- ((dimethylcarbamoyl) oxy) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5-fluoro-1H-indole-1-carboxylic acid tert-butyl ester;

Dimethylcarbamic acid (S, E) -7-amino-1- ((1- ((5-fluoro-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) -tert-butyl 2- ((3- (2- ((bis (2-methoxyethyl) carbamoyl) oxy) -7- (dimethylamino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5-fluoro-1H-indole-1-carboxylate;

bis (2-methoxyethyl) carbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((5-fluoro-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) -benzyl 2- ((3- (7- (dimethylamino) -2- ((dimethylcarbamoyl) oxy) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5-fluoro-1H-indole-1-carboxylate;

dimethylcarbamic acid (E) -7- (dimethylamino) -1- ((1- ((5-fluoro-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl-3, 3-d₂An ester;

(E) -tert-butyl 2- ((3- (7- (dimethylamino) -2- ((dimethylcarbamoyl) oxy) -7-oxohept-5-enoylamino-3, 3-d2) -2-oxopyridin-1 (2H) -yl) methyl) -5-fluoro-1H-indole-1-carboxylate;

2- [ [3- [ [ (E,2S) -7- (dimethylamino) -2- (dimethylcarbamoyloxy) -7-oxo-hept-5-enoyl ] amino ] -2-oxo-pyrazin-1-yl ] methyl ] -5-fluoro-indole-1-carboxylic acid tert-butyl ester;

N, N-dimethylcarbamic acid [ (E,1S) -6- (dimethylamino) -1- [ [4- [ (5-fluoro-1H-indol-2-yl) methyl ] -3-oxo-pyrazin-2-yl ] carbamoyl ] -6-oxo-hex-4-enyl ] ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((5-fluoro-1H-indol-2-yl) methyl) -6-oxo-1, 6-dihydropyrimidin-5-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) -2- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -4-isobutyl-1H-indole-1-carboxylic acid tert-butyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((4-isobutyl-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -2- ((3- (7-amino-2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -4-isobutyl-1H-indole-1-carboxylic acid tert-butyl ester;

(S, E) - (7-amino-1- ((1- ((4-isobutyl-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -2- ((3- (7-amino-2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -7-isobutyl-1H-indole-1-carboxylic acid tert-butyl ester;

(S, E) -2- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -7-isobutyl-1H-indole-1-carboxylic acid tert-butyl ester;

(S, E) - (7-amino-1- ((1- ((7-isobutyl-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((7-isobutyl-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((7-isobutyl-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) -2- ((3- (7- (dimethylamino) -2- ((methylcarbamoyl) oxy) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -7-isobutyl-1H-indole-1-carboxylic acid tert-butyl ester;

methylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((7-isobutyl-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -1- ((1- ((7-isobutyl-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (methylamino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) -2- ((3- (7- (dimethylamino) -7-oxo-2- ((pyrrolidine-1-carbonyl) oxy) hept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -7-isobutyl-1H-indole-1-carboxylic acid tert-butyl ester;

pyrrolidine-1-carboxylic acid (S, E) -7- (dimethylamino) -1- ((1- ((7-isobutyl-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) -7-isobutyl-2- ((3- (2- ((methoxycarbonyl) amino) -7-oxo-7- (pyrrolidin-1-yl) hept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -1H-indole-1-carboxylic acid tert-butyl ester;

(S, E) - (1- ((1- ((7-isobutyl-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxo-7- (pyrrolidin-1-yl) hept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (E) -7- (dimethylamino) -1- ((1- ((7-isobutyl-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl-3, 3-d₂An ester;

(E) -2- ((3- (7- (dimethylamino) -2- ((dimethylcarbamoyl) oxy) -7-oxohept-5-enoylamino-3, 3-d₂) -2-oxopyridin-1 (2H) -yl) methyl) -7-isobutyl-1H-indole-1-carboxylic acid tert-butyl ester;

(S, E) -2- (((7- (dimethylamino) -1- ((1- ((7-isobutyl-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamoyl) oxy) ethyl acetate;

(S, E) -2- ((3- (7- (dimethylamino) -2- (((2-hydroxyethoxy) carbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -7-isobutyl-1H-indole-1-carboxylic acid tert-butyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((7-isobutyl-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid 2-hydroxyethyl ester;

(S, E) -2- ((3- (2- (((2-hydroxyethoxy) carbonyl) amino) -7-oxo-7- (pyrrolidin-1-yl) hept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -7-isobutyl-1H-indole-1-carboxylic acid tert-butyl ester;

(S, E) - (1- ((1- ((7-isobutyl-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxo-7- (pyrrolidin-1-yl) hept-5-en-2-yl) carbamic acid 2-hydroxyethyl ester;

(S, E) -N7- (1- ((7- ((2, 4-difluorobenzyl) oxy) -1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -6- (4, 4-difluorocyclohexanecarboxamido) -N1, N1-dimethylhept-2-enediamide;

(S, E) - (1- ((1- ((7- ((2, 4-difluorobenzyl) oxy) -1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid tert-butyl ester;

(S, E) -N7- (1- ((7- ((2, 4-difluorobenzyl) oxy) -1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -N1, N1-dimethyl-6- (oxazole-2-carboxamido) hept-2-enediamide;

(S, E) -N7- (1- ((7- ((2, 4-difluorobenzyl) oxy) -1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -6- (2-methoxyacetylamino) -N1, N1-dimethylhept-2-enediamide;

(S, E) -N7- (1- ((7- ((2, 4-difluorobenzyl) oxy) -1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -N1, N1-dimethyl-6- (3,3, 3-trifluoropropionylamino) hept-2-enediamide;

(S, E) -N7- (1- ((7- ((2, 4-difluorobenzyl) oxy) -1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -6- (2-fluorobenzamido) -N1, N1-dimethylhept-2-enediamide;

(S, E) - (1- ((1- ((7- ((2, 4-difluorobenzyl) oxy) -1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -7- ((2, 4-difluorobenzyl) oxy) -2- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -1H-indole-1-carboxylic acid tert-butyl ester;

(S, E) -2- ((3- (7-amino-2- ((tert-butoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -7- ((2, 4-difluorobenzyl) oxy) -1H-indole-1-carboxylic acid tert-butyl ester;

(S, E) -2- ((3- (7-amino-2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -7- ((2, 4-difluorobenzyl) oxy) -1H-indole-1-carboxylic acid tert-butyl ester;

(S, E) -N7- (1- ((7- ((2, 4-difluorobenzyl) oxy) -1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -6- (2-fluorobenzamido) hept-2-enediamide;

(S, E) - (7-amino-1- ((1- ((7- (2, 2-difluoroethoxy) -1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (1- ((1- ((7- (2, 2-difluoroethoxy) -1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -7- (2, 2-difluoroethoxy) -2- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -1H-indole-1-carboxylic acid tert-butyl ester;

(S, E) - (7-amino-1- ((1- ((7- ((2, 4-difluorobenzyl) oxy) -1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -N7- (1- ((7- ((2, 4-difluorobenzyl) oxy) -1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -6- (2-methoxyacetylamino) hept-2-enediamide;

(S, E) -7- ((2, 4-difluorobenzyl) oxy) -2- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5-fluoro-1H-indole-1-carboxylic acid tert-butyl ester;

(S, E) - (1- ((1- ((7- ((2, 4-difluorobenzyl) oxy) -5-fluoro-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -2- ((3- (7-amino-2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -7- ((2, 4-difluorobenzyl) oxy) -5-fluoro-1H-indole-1-carboxylic acid tert-butyl ester;

(S, E) - (7-amino-1- ((1- ((7- ((2, 4-difluorobenzyl) oxy) -5-fluoro-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -7- (2, 2-difluoroethoxy) -2- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5-fluoro-1H-indole-1-carboxylic acid tert-butyl ester;

(S, E) - (1- ((1- ((7- (2, 2-difluoroethoxy) -5-fluoro-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -2- ((3- (7-amino-2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -7- (2, 2-difluoroethoxy) -5-fluoro-1H-indole-1-carboxylic acid tert-butyl ester;

(S, E) - (7-amino-1- ((1- ((7- (2, 2-difluoroethoxy) -5-fluoro-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -7- ((2, 4-difluorobenzyl) oxy) -5-fluoro-2- ((3- (2- ((methoxycarbonyl) amino) -7- (methylamino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -1H-indole-1-carboxylic acid tert-butyl ester;

(S, E) - (1- ((1- ((7- ((2, 4-difluorobenzyl) oxy) -5-fluoro-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (methylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -7- ((2, 4-difluorobenzyl) oxy) -2- ((3- (7- (dimethylamino) -2- (((2-methoxyethoxy) carbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5-fluoro-1H-indole-1-carboxylic acid tert-butyl ester;

(S, E) -7- ((2, 4-difluorobenzyl) oxy) -5-fluoro-2- ((3- (2- ((methoxycarbonyl) amino) -7-oxo-7- (pyrrolidin-1-yl) hept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -1H-indole-1-carboxylic acid tert-butyl ester;

(S, E) - (1- ((1- ((7- ((2, 4-difluorobenzyl) oxy) -5-fluoro-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxo-7- (pyrrolidin-1-yl) hept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -2- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5-fluoro-7-isobutyl-1H-indole-1-carboxylic acid tert-butyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((5-fluoro-7-isobutyl-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -1- ((1- ((7- ((2, 4-difluorobenzyl) oxy) -5-fluoro-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) -7- ((2, 4-difluorobenzyl) oxy) -2- ((3- (7- (dimethylamino) -2- (((2-methoxyethyl) (methyl) carbamoyl) oxy) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5-fluoro-1H-indole-1-carboxylic acid tert-butyl ester;

(2-methoxyethyl) (methyl) carbamic acid (S, E) -1- ((1- ((7- ((2, 4-difluorobenzyl) oxy) -5-fluoro-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) -7- ((2, 4-difluorobenzyl) oxy) -2- ((3- (7- (dimethylamino) -7-oxo-2- ((pyrrolidine-1-carbonyl) oxy) hept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5-fluoro-1H-indole-1-carboxylic acid tert-butyl ester;

pyrrolidine-1-carboxylic acid (S, E) -1- ((1- ((7- ((2, 4-difluorobenzyl) oxy) -5-fluoro-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (1- ((1- ((7- ((2, 4-difluorobenzyl) oxy) -5-fluoro-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid 2-methoxyethyl ester;

(S, E) -7- ((2, 4-difluorobenzyl) oxy) -2- ((3- (2- ((dimethylcarbamoyl) oxy) -7-oxo-7- (pyrrolidin-1-yl) hept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5-fluoro-1H-indole-1-carboxylic acid tert-butyl ester;

dimethylcarbamic acid (S, E) -1- ((1- ((7- ((2, 4-difluorobenzyl) oxy) -5-fluoro-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxo-7- (pyrrolidin-1-yl) hept-5-en-2-yl ester;

Dimethylcarbamic acid (S, E) -7-amino-1- ((1- ((7- ((2, 4-difluorobenzyl) oxy) -5-fluoro-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (1- ((1- ((5-fluoro-7-isobutyl-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxo-7- (pyrrolidin-1-yl) hept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -5-fluoro-7-isobutyl-2- ((3- (2- ((methoxycarbonyl) amino) -7-oxo-7- (pyrrolidin-1-yl) hept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -1H-indole-1-carboxylic acid tert-butyl ester;

(S, E) - (7- (bis (methyl-d)₃) Amino) -1- ((1- ((7- ((2, 4-difluoro)Benzyl) oxy) -5-fluoro-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -2- ((3- (7- (bis (methyl-d)₃) Amino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -7- ((2, 4-difluorobenzyl) oxy) -5-fluoro-1H-indole-1-carboxylic acid tert-butyl ester;

(E) -7- ((2, 4-difluorobenzyl) oxy) -2- ((3- (7- (dimethylamino) -2- ((dimethylcarbamoyl) oxy) -7-oxohept-5-enoylamino-3, 3-d ₂) -2-oxopyridin-1 (2H) -yl) methyl) -5-fluoro-1H-indole-1-carboxylic acid tert-butyl ester;

dimethylcarbamic acid (E) -1- ((1- ((7- ((2, 4-difluorobenzyl) oxy) -5-fluoro-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl-3, 3-d₂An ester;

(E) -2- ((3- (7- (dimethylamino) -2- ((dimethylcarbamoyl) oxy) -7-oxohept-5-enoylamino-3, 3-d₂) -2-oxopyridin-1 (2H) -yl) methyl) -5-fluoro-7-isobutyl-1H-indole-1-carboxylic acid tert-butyl ester;

dimethylcarbamic acid (E) -7- (dimethylamino) -1- ((1- ((5-fluoro-7-isobutyl-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl-3, 3-d₂An ester;

n, N-dimethylcarbamic acid [ (E,1S) -6- (dimethylamino) -1- [ [1- [ [ 5-fluoro-7- (3,3, 3-trifluoropropyl) -1H-indol-2-yl ] methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] ester;

(S, E) -5-fluoro-2- ((3- (2- ((methoxycarbonyl) amino) -7-oxo-7- (pyrrolidin-1-yl) hept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -7- (3,3, 3-trifluoropropyl) -1H-indole-1-carboxylic acid tert-butyl ester;

(S, E) - (1- ((1- ((5-fluoro-7- (3,3, 3-trifluoropropyl) -1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxo-7- (pyrrolidin-1-yl) hept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((5-fluoro-7- (3,3, 3-trifluoropropyl) -1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -2- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5-fluoro-7- (3,3, 3-trifluoropropyl) -1H-indole-1-carboxylic acid tert-butyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((5-fluoro-7- (trifluoromethyl) -1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) -2- ((3- (7- (dimethylamino) -2- ((dimethylcarbamoyl) oxy) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5-fluoro-7- (trifluoromethyl) -1H-indole-1-carboxylic acid tert-butyl ester;

(S, E) -2- ((3- (2- ((dimethylcarbamoyl) oxy) -7- (methylamino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5-fluoro-7- (3,3, 3-trifluoropropyl) -1H-indole-1-carboxylic acid tert-butyl ester;

dimethylcarbamic acid (S, E) -1- ((1- ((5-fluoro-7- (3,3, 3-trifluoropropyl) -1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (methylamino) -1, 7-dioxohept-5-en-2-yl ester;

2- [ [3- [ [ (E,2S) -7- (dimethylamino) -7-oxo-2- (pyrrolidine-1-carbonyloxy) hept-5-enoyl ] amino ] -2-oxo-1-pyridinyl ] methyl ] -7- (2, 2-dimethylpropyl) -5-fluoro-indole-1-carboxylic acid tert-butyl ester;

pyrrolidine-1-carboxylic acid [ (E,1S) -6- (dimethylamino) -1- [ [1- [ [7- (2, 2-dimethylpropyl) -5-fluoro-1H-indol-2-yl ] methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] ester;

(S, E) - (7- (dimethylamino) -2-methoxyethyl 1- ((1- ((5-fluoro-7-neopentyl-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamate;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((5-fluoro-7-neopentyl-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (1- ((1- ((5-fluoro-7-neopentyl-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxo-7- (pyrrolidin-1-yl) hept-5-en-2-yl) carbamic acid methyl ester;

(2-methoxyethyl) (methyl) carbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((5-fluoro-7-neopentyl-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

Pyrrolidine-1-carboxylic acid (S, E) -1- ((1- ((5-fluoro-7-neopentyl-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxo-7- (pyrrolidin-1-yl) hept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((5-fluoro-7-neopentyl-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

2- [ [3- [ [ (E,2S) -7- (dimethylamino) -2- (dimethylcarbamoyloxy) -7-oxo-hept-5-enoyl ] amino ] -2-oxo-pyrazin-1-yl ] methyl ] -7- (2, 2-dimethylpropyl) -5-fluoro-indole-1-carboxylic acid tert-butyl ester;

n, N-dimethylcarbamic acid [ (E,1S) -6- (dimethylamino) -1- [ [4- [ [7- (2, 2-dimethylpropyl) -5-fluoro-1H-indol-2-yl ] methyl ] -3-oxo-pyrazin-2-yl ] carbamoyl ] -6-oxo-hex-4-enyl ] ester;

(S, E) -2- ((5- (7- (dimethylamino) -2- ((dimethylcarbamoyl) oxy) -7-oxohept-5-enoylamino) -6-oxopyrimidin-1 (6H) -yl) methyl) -5-fluoro-7-neopentyl-1H-indole-1-carboxylic acid tert-butyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((5-fluoro-7-neopentyl-1H-indol-2-yl) methyl) -6-oxo-1, 6-dihydropyrimidin-5-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) -2- ((3- (7- (dimethylamino) -2- ((dimethylcarbamoyl) oxy) -7-oxohept-5-enoylamino) -2-oxopyrazin-1 (2H) -yl) methyl) -5-fluoro-7- (3,3, 3-trifluoropropyl) -1H-indole-1-carboxylic acid tert-butyl ester;

(S, E) -2- ((5- (7- (dimethylamino) -2- ((dimethylcarbamoyl) oxy) -7-oxohept-5-enoylamino) -6-oxopyrimidin-1 (6H) -yl) methyl) -5-fluoro-7- (3,3, 3-trifluoropropyl) -1H-indole-1-carboxylic acid tert-butyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((5-fluoro-7- (3,3, 3-trifluoropropyl) -1H-indol-2-yl) methyl) -6-oxo-1, 6-dihydropyrimidin-5-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) -2- ((5- (2- ((dimethylcarbamoyl) oxy) -7- (methylamino) -7-oxohept-5-enoylamino) -6-oxopyrimidin-1 (6H) -yl) methyl) -5-fluoro-7- (3,3, 3-trifluoropropyl) -1H-indole-1-carboxylic acid tert-butyl ester;

dimethylcarbamic acid (S, E) -1- ((1- ((5-fluoro-7- (3,3, 3-trifluoropropyl) -1H-indol-2-yl) methyl) -6-oxo-1, 6-dihydropyrimidin-5-yl) amino) -7- (methylamino) -1, 7-dioxohept-5-en-2-yl ester;

n, N-dimethylcarbamic acid [ (E,1S) -6- (dimethylamino) -1- [ [1- [ (5-fluoro-1-isobutyl-indol-2-yl) methyl ] -6-oxo-pyrimidin-5-yl ] carbamoyl ] -6-oxo-hex-4-enyl ] ester;

Dimethylcarbamic acid (S, E) -1- ((1- ((1- ((1-benzyl-5-fluoro-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -1- ((1- ((1- (cyclopropylmethyl) -5-fluoro-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((5-fluoro-1-methyl-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((5-fluoro-1- (4-fluorobenzyl) -1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((1-ethyl-5-fluoro-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -1- ((1- ((1- ((1- (2, 4-difluorobenzyl) -5-fluoro-1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

2- [ [3- [ [ (E,2S) -7- (dimethylamino) -2- (dimethylcarbamoyloxy) -7-oxo-hept-5-enoyl ] amino ] -2-oxo-1-pyridinyl ] methyl ] -5-fluoro-indole-1-carboxylic acid methyl ester;

(S, E) -2- ((3- (7- (dimethylamino) -2- ((dimethylcarbamoyl) oxy) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5-fluoro-1H-indole-1-carboxylic acid 2, 4-difluorobenzyl ester;

n, N-dimethylcarbamic acid [ (E,1S) -6- (dimethylamino) -1- [ [4- [ (5-fluoro-1-isobutyl-indol-2-yl) methyl ] -3-oxo-pyrazin-2-yl ] carbamoyl ] -6-oxo-hex-4-enyl ] ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((4- ((1-ethyl-5-fluoro-1H-indol-2-yl) methyl) -3-oxo-3, 4-dihydropyrazin-2-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -1- ((4- ((1-benzyl-5-fluoro-1H-indol-2-yl) methyl) -3-oxo-3, 4-dihydropyrazin-2-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -1- ((4- ((1- (cyclopropylmethyl) -5-fluoro-1H-indol-2-yl) methyl) -3-oxo-3, 4-dihydropyrazin-2-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((4- ((5-fluoro-1- (4-fluorobenzyl) -1H-indol-2-yl) methyl) -3-oxo-3, 4-dihydropyrazin-2-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

Dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((5-fluoro-1-isobutyl-1H-indol-2-yl) methyl) -6-oxo-1, 6-dihydropyrimidin-5-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -1- ((4- ((1- (2, 4-difluorobenzyl) -5-fluoro-1H-indol-2-yl) methyl) -3-oxo-3, 4-dihydropyrazin-2-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

n- [2- [ tert-butoxycarbonyl (methyl) amino ] ethyl ] -N-methyl-carbamic acid [ (E,1S) -6- (dimethylamino) -1- [ [1- [ (5-fluoro-1-methyl-indol-2-yl) methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] ester;

n- [2- (dimethylamino) ethyl ] -N-methyl-carbamic acid [ (E,1S) -6- (dimethylamino) -1- [ [1- [ (5-fluoro-1-methyl-indol-2-yl) methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] ester;

(S, E) -7- ((3- (7-amino-2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -1H-indole-1-carboxylic acid tert-butyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((7-isobutylbenzo [ d ] oxazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7-amino-1- ((1- ((7-isobutylbenzo [ d ] oxazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((4-isobutylbenzo [ d ] oxazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7-amino-1- ((1- ((4-isobutylbenzo [ d ] oxazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((7-isobutylbenzo [ d ] oxazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid 2-hydroxyethyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((7-isobutylbenzo [ d ] thiazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7-amino-1- ((1- ((7-isobutylbenzo [ d ] thiazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -2-hydroxyethyl 1- ((1- ((7-isobutylbenzo [ d ] thiazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamate;

(S, E) - (1- ((1- ((7- ((2, 4-difluorobenzyl) oxy) benzo [ d ] thiazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid tert-butyl ester;

(S, E) -N7- (1- ((7- ((2, 4-difluorobenzyl) oxy) benzo [ d ] thiazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -N1, N1-dimethyl-6- (oxazole-2-carboxamido) hept-2-enediamide;

(S, E) -N7- (1- ((7- ((2, 4-difluorobenzyl) oxy) benzo [ d ] thiazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -6- (4, 4-difluorocyclohexane-1-carboxamido) -N1, N1-dimethylhept-2-enediamide;

(S, E) -N7- (1- ((7- ((2, 4-difluorobenzyl) oxy) benzo [ d ] thiazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -6- (2-fluorobenzamido) -N1, N1-dimethylhept-2-enediamide;

(S, E) - (7-amino-1- ((1- ((7- ((2, 4-difluorobenzyl) oxy) benzo [ d ] thiazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (1- ((1- ((7- ((2, 4-difluorobenzyl) oxy) benzo [ d ] thiazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -N7- (1- ((7- ((2, 4-difluorobenzyl) oxy) benzo [ d ] thiazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -6- (2-methoxyacetylamino) -N1, N1-dimethylhept-2-enediamide;

(S, E) - (7-amino-1- ((1- ((7- (2, 2-difluoroethoxy) benzo [ d ] thiazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (1- ((1- ((7- (2, 2-difluoroethoxy) benzo [ d ] thiazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7-amino-1, 7-dioxo-1- ((2-oxo-1- ((7- (1,1,2, 2-tetrafluoroethoxy) benzo [ d ] thiazol-2-yl) methyl) -1, 2-dihydropyridin-3-yl) amino) hept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1, 7-dioxo-1- ((2-oxo-1- ((7- (1,1,2, 2-tetrafluoroethoxy) benzo [ d ] thiazol-2-yl) methyl) -1, 2-dihydropyridin-3-yl) amino) hept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1, 7-dioxo-1- ((2-oxo-1- ((7- (2,2, 2-trifluoroethoxy) benzo [ d ] thiazol-2-yl) methyl) -1, 2-dihydropyridin-3-yl) amino) hept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7-amino-1, 7-dioxo-1- ((2-oxo-1- ((7- (2,2, 2-trifluoroethoxy) benzo [ d ] thiazol-2-yl) methyl) -1, 2-dihydropyridin-3-yl) amino) hept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7-amino-1- ((1- ((7- ((2, 4-difluorobenzyl) oxy) benzo [ d ] thiazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid tert-butyl ester;

(S, E) -N7- (1- ((7- ((2, 4-difluorobenzyl) oxy) benzo [ d ] thiazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -6- (2-methoxyacetylamino) hept-2-enediamide;

(S, E) -N7- (1- ((7- ((2, 4-difluorobenzyl) oxy) benzo [ d ] thiazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -6- (2-fluorobenzamido) hept-2-enediamide;

(S, E) - (7- (dimethylamino) -1- ((1- ((5-fluorobenzo [ d ] thiazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7-amino-1- ((1- ((5-fluorobenzo [ d ] thiazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (1- ((1- ((5-fluorobenzo [ d ] thiazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxo-7- (pyrrolidin-1-yl) hept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -methyl (1- ((1- ((7- ((2, 4-difluorophenoxy) methyl) benzo [ d ] thiazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamate;

(S, E) - (1- ((1- (benzo [ d ] thiazol-2-ylmethyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid 2-hydroxyethyl ester;

(S, E) -2- ((3- (7- (dimethylamino) -2- (((2-hydroxyethoxy) carbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -1H-indole-1-carboxylic acid tert-butyl ester;

(S, E) - (7-amino-1- ((1- (benzo [ d ] oxazol-2-ylmethyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid 2-hydroxyethyl ester;

(S, E) - (7-amino-1- ((1- (benzo [ d ] thiazol-2-ylmethyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid 2-hydroxyethyl ester;

(S, E) - (1- ((1- ((1H-indol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7-amino-1, 7-dioxohept-5-en-2-yl) carbamic acid 2-hydroxyethyl ester;

(S, E) -2- ((3- (7-amino-2- (((2-hydroxyethoxy) carbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -1H-indole-1-carboxylic acid tert-butyl ester;

(S, E) - (7-amino-1- ((1- ((7- ((2, 4-difluorobenzyl) oxy) -5-fluorobenzo [ d ] thiazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -2- ((3- (7- (dimethylamino) -2- (((2-hydroxyethoxy) carbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -1H-indole-1-carboxylic acid tert-butyl ester;

(S, E) - (1- ((1- ((7- ((2, 4-difluorobenzyl) oxy) -5-fluorobenzo [ d ] thiazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (methylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

methyl N- [ (E) -1- [ [ [1- [ (5, 7-difluoro-4-isobutyl-1H-benzimidazol-2-yl) methyl ] -2-oxo-3-pyridinyl ] amino ] methyl ] -6- (dimethylamino) -6-oxo-hex-4-enyl ] carbamate;

methyl N- [ (E,1S) -1- [ [1- [ [4- (2, 4-difluorophenoxy) -5, 6-difluoro-1H-benzimidazol-2-yl ] methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6- (dimethylamino) -6-oxo-hex-4-enyl ] carbamate;

(S, E) - (1- ((1- ((5, 6-difluoro-7-isopropoxy-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (1- ((1- ((7- (benzyloxy) -5, 6-difluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (1- ((1- ((7- ((2, 4-difluorobenzyl) oxy) -5, 6-difluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (1- ((1- ((5, 6-difluoro-7-phenoxy-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -1- ((1- ((5, 6-difluoro-7-isopropoxy-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -1- ((1- ((4- (2, 4-difluorophenoxy) -5, 6-difluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -1- ((1- ((4- ((2, 4-difluorobenzyl) oxy) -5, 6-difluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

4- (2, 4-difluorophenoxy) -2- [ [3- [ [ (E,2S) -7- (dimethylamino) -2- (methoxycarbonylamino) -7-oxo-hept-5-enoyl ] amino ] -2-oxo-1-pyridinyl ] methyl ] -5, 6-difluoro-benzimidazole-1-carboxylic acid tert-butyl ester;

(S, E) -tert-butyl 2- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5, 6-difluoro-4-isopropoxy-1H-benzo [ d ] imidazole-1-carboxylate;

(S, E) -4- (benzyloxy) -2- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5, 6-difluoro-1H-benzo [ d ] imidazole-1-carboxylic acid tert-butyl ester;

(S, E) -4- ((2, 4-difluorobenzyl) oxy) -2- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5, 6-difluoro-1H-benzo [ d ] imidazole-1-carboxylic acid tert-butyl ester;

(S, E) -tert-butyl 2- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5, 6-difluoro-4-phenoxy-1H-benzo [ d ] imidazole-1-carboxylate;

(S, E) -4- ((2, 4-difluorobenzyl) oxy) -2- ((3- (7- (dimethylamino) -2- ((dimethylcarbamoyl) oxy) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5, 6-difluoro-1H-benzo [ d ] imidazole-1-carboxylic acid tert-butyl ester;

2- [ [3- [ [ (E,2S) -7- (dimethylamino) -2- (methoxycarbonylamino) -7-oxo-hept-5-enoyl ] amino ] -2-oxo-1-pyridinyl ] methyl ] -4- (2, 2-dimethylpropyl) -5, 6-difluoro-benzimidazole-1-carboxylic acid tert-butyl ester;

methyl N- [ (E,1S) -6- (dimethylamino) -1- [ [1- [ [4- (2, 2-dimethylpropyl) -5, 6-difluoro-1H-benzimidazol-2-yl ] methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] carbamate;

(S, E) -tert-butyl 2- ((3- (7- (dimethylamino) -2- ((dimethylcarbamoyl) oxy) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5, 6-difluoro-4-neopentyl-1H-benzo [ d ] imidazole-1-carboxylate;

dimethylcarbamic acid (S, E) -1- ((1- ((5, 6-difluoro-4-neopentyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

2- [ [3- [ [ (E,2S) -7- (dimethylamino) -2- (methoxycarbonylamino) -7-oxo-hept-5-enoyl ] amino ] -2-oxo-1-pyridinyl ] methyl ] -5, 7-difluoro-4-phenoxy-benzimidazole-1-carboxylic acid tert-butyl ester;

(S, E) -4- (2, 4-difluorophenoxy) -2- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5, 7-difluoro-1H-benzo [ d ] imidazole-1-carboxylic acid tert-butyl ester;

Methyl N- [ (E,1S) -1- [ [1- [ (5, 7-difluoro-4-phenoxy-1H-benzimidazol-2-yl) methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6- (dimethylamino) -6-oxo-hex-4-enyl ] carbamate;

(S, E) -4- (benzyloxy) -2- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5, 7-difluoro-1H-benzo [ d ] imidazole-1-carboxylic acid tert-butyl ester;

(S, E) -tert-butyl 2- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -5, 7-difluoro-4-isopropoxy-1H-benzo [ d ] imidazole-1-carboxylate;

(S, E) - (1- ((1- ((4- (2, 4-difluorophenoxy) -5, 7-difluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (1- ((1- ((4- (benzyloxy) -5, 7-difluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (1- ((1- ((4- ((2, 4-difluorobenzyl) oxy) -5, 7-difluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

Dimethylcarbamic acid (S, E) -1- ((1- ((7- ((2, 4-difluorobenzyl) oxy) -4, 6-difluoro-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

methyl N- [ (E,1S) -6- (dimethylamino) -6-oxo-1- [ [ 2-oxo-1- [ (6-phenoxy-9H-purin-8-yl) methyl ] -3-pyridinyl ] carbamoyl ] hex-4-enyl ] carbamate;

(S, E) -6- (2, 4-difluorophenoxy) -8- ((3- (7- (dimethylamino) -2- ((methoxycarbonyl) amino) -7-oxohept-5-enoylamino) -2-oxopyridin-1 (2H) -yl) methyl) -9H-purine-9-carboxylic acid tert-butyl ester;

(S, E) - (1- ((1- ((6- (2, 4-difluorophenoxy) -9H-purin-8-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((6-isopropoxy-9H-purin-8-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((6-isobutoxy-9H-purin-8-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

Methyl N- [ (E,1S) -1- [ [1- [ (6-benzyloxy-9H-purin-8-yl) methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6- (dimethylamino) -6-oxo-hex-4-enyl ] carbamate;

(S, E) - (1- ((1- ((6- ((2, 4-difluorobenzyl) oxy) -9H-purin-8-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -1- ((1- ((6- ((2, 4-difluorobenzyl) oxy) -9H-purin-8-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

methyl N- [ (E,1S) -1- [ [1- [ (6-benzyl-9H-purin-8-yl) methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6- (dimethylamino) -6-oxo-hex-4-enyl ] carbamate;

(S, E) - (7- (dimethylamino) -1, 7-dioxo-1- ((2-oxo-1- ((6- (3,3, 3-trifluoropropyl) -9H-purin-8-yl) methyl) -1, 2-dihydropyridin-3-yl) amino) hept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (1- ((1- ((6- (cyclopropylmethyl) -9H-purin-8-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

((2S, E) -7- (dimethylamino) -1, 7-dioxo-1- ((2-oxo-1- ((9- (tetrahydro-2H-pyran-2-yl) -6- (3,3, 3-trifluoropropyl) -9H-purin-8-yl) methyl) -1, 2-dihydropyridin-3-yl) amino) hept-5-en-2-yl) carbamic acid methyl ester;

Dimethylcarbamic acid (2S, E) -7- (dimethylamino) -1, 7-dioxo-1- ((2-oxo-1- ((9- (tetrahydro-2H-pyran-2-yl) -6- (3,3, 3-trifluoropropyl) -9H-purin-8-yl) methyl) -1, 2-dihydropyridin-3-yl) amino) hept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1, 7-dioxo-1- ((2-oxo-1- ((6- (3,3, 3-trifluoropropyl) -9H-purin-8-yl) methyl) -1, 2-dihydropyridin-3-yl) amino) hept-5-en-2-yl ester;

n- [ (E,1S) -6- (dimethylamino) -1- [ [1- [ [6- (2, 2-dimethylpropyl) -9H-purin-8-yl ] methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((6-neopentyl-9H-purin-8-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((6-isopentyl-9H-purin-8-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (1- ((1- ((6- (2-cyclohexylethyl) -7H-purin-8-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((6- (3, 3-dimethylbutyl) -9H-purin-8-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((6- (3, 3-dimethylbutyl) -9H-purin-8-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (2S, E) -7- (dimethylamino) -1- ((1- ((6- (3, 3-dimethylbutyl) -9- (tetrahydro-2H-pyran-2-yl) -9H-purin-8-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

((2S, E) -7- (dimethylamino) -1- ((1- ((6- (3, 3-dimethylbutyl) -9- (tetrahydro-2H-pyran-2-yl) -9H-purin-8-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (2S, E) -7- (dimethylamino) -1- ((1- ((6-isopentyl-9- (tetrahydro-2H-pyran-2-yl) -9H-purin-8-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((6-isopentyl-9H-purin-8-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

Methyl N- [ (E,1S) -6- (dimethylamino) -1- [ [1- [ (4-isobutyl-5H-pyrrolo [3,2-d ] pyrimidin-6-yl) methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] carbamate;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((4-isobutyl-5H-pyrrolo [3,2-d ] pyrimidin-6-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -1, 7-dioxo-1- ((2-oxo-1- ((4- (3,3, 3-trifluoropropyl) -5H-pyrrolo [3,2-d ] pyrimidin-6-yl) methyl) -1, 2-dihydropyridin-3-yl) amino) hept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1, 7-dioxo-1- ((2-oxo-1- ((4- (3,3, 3-trifluoropropyl) -5H-pyrrolo [3,2-d ] pyrimidin-6-yl) methyl) -1, 2-dihydropyridin-3-yl) amino) hept-5-en-2-yl ester;

((2S, E) -7- (dimethylamino) -1- ((1- ((2-methyl-6-neopentyl-9- (tetrahydro-2H-pyran-2-yl) -9H-purin-8-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((2-methyl-6-neopentyl-9H-purin-8-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

Dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((2-methyl-6-neopentyl-9H-purin-8-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (1- ((1- ((6- (cyclohexylmethyl) -9H-purin-8-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -1- ((1- ((6- (cyclohexylmethyl) -9H-purin-8-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((4-isobutyl-2-methyl-5H-pyrrolo [3,2-d ] pyrimidin-6-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((4-isobutyl-2-methyl-5H-pyrrolo [3,2-d ] pyrimidin-6-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1, 7-dioxo-1- ((2-oxo-1- ((6- (3,3, 3-trifluoro-2- (trifluoromethyl) propyl) -9H-purin-8-yl) methyl) -1, 2-dihydropyridin-3-yl) amino) hept-5-en-2-yl ester;

2-methoxyethyl N- [ (E,1S) -6- (dimethylamino) -1- [ [1- [ (6-fluoro-7-isobutyl-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] carbamate;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((6-fluoro-7-isobutyl-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((6-fluoro-7-isobutyl-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) -6- (3, 3-dimethylureido) -N7- (1- ((6-fluoro-7-isobutyl-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) -N1, N1-dimethylhept-2-enediamide;

methyl N- [ (E,1S) -6- (dimethylamino) -1- [ [1- [ (6-fluoro-7-isobutyl-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl ] -6-methyl-2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] carbamate;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((6-fluoro-7-isobutyl-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl) -6-methyl-2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (1- ((6-chloro-1- ((6-fluoro-7-isobutyl-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -1- ((6-chloro-1- ((6-fluoro-7-isobutyl-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (1- ((1- ((7- (cyclobutylmethyl) -6-fluoro-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -1- ((1- ((7- (cyclobutylmethyl) -6-fluoro-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((6-fluoro-7-isopropoxy-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((6-fluoro-7-isopropoxy-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((6-fluoro-7-isobutoxy-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((6-fluoro-7-isobutoxy-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (1- ((1- ((7- (benzyloxy) -6-fluoro-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -1- ((1- ((7- (benzyloxy) -6-fluoro-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

methyl N- [ (E,1S) -1- [ [1- [ (6-chloro-7-isobutyl-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6- (dimethylamino) -6-oxo-hex-4-enyl ] carbamate;

dimethylcarbamic acid (S, E) -1- ((1- ((6-chloro-7-isobutyl-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (1- ((1- ((7- (cyclopropylmethyl) -6-fluoro-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((7-isobutyl-6- (trifluoromethyl) -1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((7-isobutyl-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((7-isobutyl-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((7-isobutyl-1H-pyrrolo [3,2-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(E) methyl (7- (dimethylamino) -1- ((1- ((7-isobutyl-1H-pyrrolo [3,2-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamate;

(S, E) - (7- (dimethylamino) -1- ((1- ((7- (2-methylprop-1-en-1-yl) -1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((7- (2-methylprop-1-en-1-yl) -1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((7- (2-methylprop-1-en-1-yl) -6- (trifluoromethyl) -1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

methyl N- [ (E,1S) -6- (dimethylamino) -1- [ [1- [ (6-fluoro-7-isobutyl-3-methyl-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] carbamate;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((6-fluoro-7-isobutyl-3-methyl-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((6-fluoro-7-isobutyl-3-methyl-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl) -6-methyl-2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((6-fluoro-7-isobutyl-3-methyl-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl) -6-methyl-2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((6-fluoro-7-isobutyl-5-methyl-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((6-fluoro-7-isobutyl-5-methyl-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((6-fluoro-7- (3,3, 3-trifluoropropyl) -1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((6-fluoro-7- (3,3, 3-trifluoropropyl) -1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((4-fluoro-7-isobutyl-1H-pyrrolo [2,3-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((4-fluoro-7-isobutyl-1H-pyrrolo [2,3-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((4-fluoro-7-isobutyl-1H-pyrrolo [2,3-c ] pyridin-2-yl) methyl) -6-methyl-2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((4-fluoro-7-isobutyl-1H-pyrrolo [2,3-c ] pyridin-2-yl) methyl) -6-methyl-2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -1- ((6-chloro-1- ((4-fluoro-7-isobutyl-1H-pyrrolo [2,3-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (1- ((6-chloro-1- ((4-fluoro-7-isobutyl-1H-pyrrolo [2,3-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((4-fluoro-7- (2-methylprop-1-en-1-yl) -1H-pyrrolo [2,3-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

Dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((4-fluoro-7- (2-methylprop-1-en-1-yl) -1H-pyrrolo [2,3-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

methyl N- [ (E,1S) -6- (dimethylamino) -1- [ [1- [ (7-isobutyl-1H-pyrrolo [2,3-c ] pyridin-2-yl) methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] carbamate;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((7-isobutyl-1H-pyrrolo [2,3-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((6- (dimethylamino) -2-methyl-9H-purin-8-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

methyl N- [ (E,1S) -6- (dimethylamino) -1- [ [1- [ (4-isobutyl-1H-benzimidazol-2-yl) methyl ] -6-methyl-2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] carbamate;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((7-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -6-methyl-2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (1- ((6-chloro-1- ((4-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -1- ((6-chloro-1- ((7-isobutyl-1H-benzo [ d ] imidazol-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

methyl N- [ (E,1S) -6- (dimethylamino) -1- [ [1- [ (7-fluoro-4-isobutyl-1H-imidazo [4,5-c ] pyridin-2-yl) methyl ] -6-methyl-2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] carbamate;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((7-fluoro-4-isobutyl-1H-imidazo [4,5-c ] pyridin-2-yl) methyl) -6-methyl-2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (1- ((1- ((7-fluoro-4-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -6-methyl-2-oxo-1, 2-dihydropyridin-3-yl) amino) -6- (methanesulfonyl) -1-oxohex-5-en-2-yl) carbamic acid methyl ester;

methyl N- [ (E,1S) -1- [ [ 6-chloro-1- [ (7-fluoro-4-isobutyl-1H-imidazo [4,5-c ] pyridin-2-yl) methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6- (dimethylamino) -6-oxo-hex-4-enyl ] carbamate;

N, N-dimethylcarbamic acid [ (E,1S) -1- [ [ 6-chloro-1- [ (7-fluoro-4-isobutyl-1H-imidazo [4,5-c ] pyridin-2-yl) methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6- (dimethylamino) -6-oxo-hex-4-enyl ] ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((7-fluoro-4- (3,3, 3-trifluoropropyl) -3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((7-fluoro-4- (3,3, 3-trifluoropropyl) -3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -6-methyl-2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((7-fluoro-4- (3,3, 3-trifluoropropyl) -3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -6-methyl-2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (1- ((6-chloro-1- ((7-fluoro-4- (3,3, 3-trifluoropropyl) -3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -1- ((6-chloro-1- ((7-fluoro-4- (3,3, 3-trifluoropropyl) -3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (1- ((1- ((4- (cyclopropylmethyl) -7-fluoro-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -1- ((1- ((4- (cyclopropylmethyl) -7-fluoro-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (1- ((1- ((4- (cyclopropylmethyl) -7-fluoro-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -6-methyl-2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -1- ((1- ((4- (cyclopropylmethyl) -7-fluoro-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -6-methyl-2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (1- ((6-chloro-1- ((4- (cyclopropylmethyl) -7-fluoro-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -1- ((6-chloro-1- ((4- (cyclopropylmethyl) -7-fluoro-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

Methyl N- [ (E,1S) -6- (dimethylamino) -1- [ [1- [ (7-fluoro-4-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl ] -5-methyl-2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] carbamate;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((7-fluoro-4-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -5-methyl-2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (1- ((5-chloro-1- ((7-fluoro-4-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -1- ((5-chloro-1- ((7-fluoro-4-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -1- ((5-fluoro-1- ((7-fluoro-4-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((5-fluoro-1- ((7-fluoro-4-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((7-fluoro-4-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -6-isobutyl-2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((7-fluoro-4-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -6-isobutyl-2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((7-fluoro-4-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -6-isopropyl-2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((7-fluoro-4-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -6-isopropyl-2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((6-ethyl-1- ((7-fluoro-4-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -1- ((6-ethyl-1- ((7-fluoro-4-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((7-fluoro-4-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-6-propyl-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((7-fluoro-4-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-6-propyl-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((7-fluoro-4-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -5, 6-dimethyl-2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((7-fluoro-4-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -5, 6-dimethyl-2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((7-fluoro-4-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-6- (trifluoromethyl) -1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((7-fluoro-4-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-6- (trifluoromethyl) -1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((7-fluoro-4-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -6- (methoxymethyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((7-fluoro-4-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -6- (hydroxymethyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((7-fluoro-4-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -6- (hydroxymethyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (7- (dimethylamino) -1- ((6-fluoro-1- ((7-fluoro-4-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((6-fluoro-1- ((7-fluoro-4-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -1- ((5-fluoro-1- ((7-fluoro-4-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -6-methyl-2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

Dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((5-fluoro-1- ((7-fluoro-4-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -6-methyl-2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((6-fluoro-7-isobutyl-3H-imidazo [4,5-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((6-fluoro-7-isobutyl-1H-imidazo [4,5-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((6-fluoro-7-isobutyl-3H-imidazo [4,5-b ] pyridin-2-yl) methyl) -6-methyl-2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((6-fluoro-7-isobutyl-1H-imidazo [4,5-b ] pyridin-2-yl) methyl) -6-methyl-2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -1- ((6-chloro-1- ((6-fluoro-7-isobutyl-3H-imidazo [4,5-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (1- ((6-chloro-1- ((6-fluoro-7-isobutyl-1H-imidazo [4,5-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

n- [2- (dimethylamino) ethyl ] -N-methyl-carbamic acid [ (E,1S) -6- (dimethylamino) -1- [ [1- [ (6-fluoro-7-isobutyl-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] ester;

2- (dimethylamino) ethyl N- [ (E,1S) -6- (dimethylamino) -1- [ [1- [ (6-fluoro-7-isobutyl-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] carbamate;

Dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((6-fluoro-7-isobutyl-3-methyl-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((7-fluoro-4- (3,3, 3-trifluoropropyl) -3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

(S, E) - (1- ((6-chloro-1- ((7-fluoro-4-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

dimethylcarbamic acid (S, E) -1- ((6-chloro-1- ((7-fluoro-4-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -2-oxo-1, 2-dihydropyridin-3-yl) amino) -7- (dimethylamino) -1, 7-dioxohept-5-en-2-yl ester;

dimethylcarbamic acid (S, E) -7- (dimethylamino) -1- ((1- ((7-fluoro-4-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -6-methyl-2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl ester;

(S, E) - (7- (dimethylamino) -1- ((1- ((7-fluoro-4-isobutyl-3H-imidazo [4,5-c ] pyridin-2-yl) methyl) -6-methyl-2-oxo-1, 2-dihydropyridin-3-yl) amino) -1, 7-dioxohept-5-en-2-yl) carbamic acid methyl ester;

N, N-dimethylcarbamic acid [ (E,1S) -6- (dimethylamino) -1- [ [1- [ (4-isobutyl-1H-benzimidazol-2-yl) methyl ] -6-methyl-2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] ester;

n, N-dimethylcarbamic acid [ (E,1S) -6- (dimethylamino) -1- [ [1- [ (7-fluoro-4-isobutyl-1H-imidazo [4,5-c ] pyridin-2-yl) methyl ] -6-methyl-2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] ester; or

N, N-dimethylcarbamic acid [ (E,1S) -6- (dimethylamino) -1- [ [1- [ (6-fluoro-7-isobutyl-3-methyl-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] ester;

or a pharmaceutically acceptable salt thereof.

17. A compound according to claim 1, or a pharmaceutically acceptable salt thereof, which is:

methyl N- [ (E,1S) -6- (dimethylamino) -1- [ [1- [ (4-isobutyl-1H-benzimidazol-2-yl) methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] carbamate;

methyl N- [ (E,1S) -6- (dimethylamino) -1- [ [1- [ (4-isobutyl-1H-benzimidazol-2-yl) methyl ] -6-methyl-2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] carbamate;

n, N-dimethylcarbamic acid [ (E,1S) -6- (dimethylamino) -1- [ [1- [ (4-isobutyl-1H-benzimidazol-2-yl) methyl ] -6-methyl-2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] ester;

Methyl N- [ (E,1S) -1- [ [ 6-chloro-1- [ (7-fluoro-4-isobutyl-1H-imidazo [4,5-c ] pyridin-2-yl) methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6- (dimethylamino) -6-oxo-hex-4-enyl ] carbamate;

n, N-dimethylcarbamic acid [ (E,1S) -1- [ [ 6-chloro-1- [ (7-fluoro-4-isobutyl-1H-imidazo [4,5-c ] pyridin-2-yl) methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6- (dimethylamino) -6-oxo-hex-4-enyl ] ester;

methyl N- [ (E,1S) -6- (dimethylamino) -1- [ [1- [ (7-fluoro-4-isobutyl-1H-imidazo [4,5-c ] pyridin-2-yl) methyl ] -6-methyl-2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] carbamate;

methyl N- [ (E,1S) -6- (dimethylamino) -1- [ [1- [ (6-fluoro-7-isobutyl-3-methyl-1H-pyrrolo [3,2-b ] pyridin-2-yl) methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] carbamate; or

Or a pharmaceutically acceptable salt thereof.

18. A compound which is:

or a pharmaceutically acceptable salt thereof.

19. A compound which is:

or a pharmaceutically acceptable salt thereof.

20. A compound which is:

or a pharmaceutically acceptable salt thereof.

21. A compound which is:

or a pharmaceutically acceptable salt thereof.

22. A compound which is:

or a pharmaceutically acceptable salt thereof.

23. A compound which is:

or a pharmaceutically acceptable salt thereof.

24. A compound which is:

or a pharmaceutically acceptable salt thereof.

25. A compound which is:

or a pharmaceutically acceptable salt thereof.

26. A compound which is:

or a pharmaceutically acceptable salt thereof.

27. A pharmaceutical composition comprising a compound according to any one of claims 1-26, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

28. A method of treating a disease or condition mediated by transglutaminase 2 in a patient in need of such treatment, said method comprising administering to the patient a therapeutically effective amount of a compound according to any one of claims 1-26, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition according to claim 27.

29. The method according to claim 28, wherein said transglutaminase 2 mediated disease or disorder is selected from the group consisting of celiac disease, neurodegenerative disease, ocular disease, cancer, and fibrosis.

30. The method according to claim 29, wherein the neurodegenerative disease is selected from parkinson's disease, huntington's disease, and alzheimer's disease.

31. The method according to claim 29, wherein said ocular disease is selected from the group consisting of macular degeneration, glaucoma, cataracts, and uveitis.

32. The method according to claim 29, wherein the cancer is selected from the group consisting of melanoma, glioblastoma, meningioma, pancreatic cancer, renal cell carcinoma, and breast cancer.

33. The method according to claim 29, wherein the fibrosis is selected from the group consisting of renal fibrosis, idiopathic pulmonary fibrosis and liver fibrosis.

34. A compound according to any one of claims 1 to 26, or a pharmaceutically acceptable salt thereof, for use in therapy.

35. A compound according to any one of claims 1 to 26, or a pharmaceutically acceptable salt thereof, for use in the treatment of celiac disease, neurodegenerative disease, ocular disease, cancer or fibrosis.

36. Use of a compound according to any one of claims 1 to 26, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment of a disease or condition mediated by transglutaminase 2.

37. The use according to claim 36, wherein the disease or disorder is celiac disease, neurodegenerative disease, ocular disease, cancer or fibrosis.

Background

Transglutaminase 2(TG2) is a member of the human transglutaminase family, which is abundantly expressed in various tissues and found both in intracellular and extracellular locations. It has catalytic activity for cross-linking glutamine side chains on substrate peptides or proteins with amines bound to small biological molecules or proteins, which requires fine post-translational regulation. TG2 is involved in the pathogenesis of a range of human diseases, particularly inflammatory diseases.

Disclosure of Invention

Described herein are inhibitors of transglutaminase 2(TG 2). Also disclosed herein are methods of synthesizing such TG2 inhibitors and methods of treating diseases using such TG2 inhibitors, wherein TG2 inhibition provides a therapeutic benefit to patients suffering from the disease. Further described are pharmaceutical formulations comprising TG2 inhibitors.

Another aspect is a compound having the structure of formula (Q), or a pharmaceutically acceptable salt or solvate thereof:

Wherein:

is a 9-membered bicyclic heteroaryl ring;

x, Y and Z are selected from ═ C (R)¹¹) -and-N-wherein at least two of X, Y and Z are ═ C (R)¹¹)-；

W is-C (O) NR¹R²or-S (O)₂R¹²；

R³selected from-N (H) C (O) OR⁵、-OC(O)NR⁶R⁷、-N(H)C(O)NR⁶R⁷and-N (H) C (O) R⁸；

R⁵is selected from C_1-6Alkyl, -C_1-6alkyl-OH, -C_1-6alkyl-O-C_1-6Alkyl, -C_1-6alkyl-O-C (O) C_1-6Alkyl radical, C_2-9Heterocycloalkyl, -C_1-6alkyl-C_2-9Heterocycloalkyl, phenyl, -C_1-6Alkyl-phenyl and C_2-9Heteroaryl group, wherein C_2-9Heterocycloalkyl, -C _1-6alkyl-C_2-9Heterocycloalkyl, phenyl, -C_1-6Alkyl-phenyl and C_2-9Heteroaryl is optionally substituted with one or two substituents independently selected from halogen and C_1-6A group of alkyl groups;

each R⁹Independently selected from C_1-10Alkyl radical, C_1-10Haloalkyl, C_3-12Cycloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl, phenyl, -C_1-6Alkyl-phenyl and C_2-9Heteroaryl, in which phenyl, -C_1-6Alkyl-phenyl and C_2-9Heteroaryl is optionally substituted with one or two substituents independently selected from halogen and C_1-6A group of alkyl groups;

each R¹⁰Independently selected from H, C_1-10Alkyl radical, C_1-10Haloalkyl, C_3-12Cycloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl, phenyl, -C_1-6Alkyl-phenyl and C_2-9Heteroaryl, in which phenyl, -C _1-6Alkyl radical-phenyl and C_2-9Heteroaryl is optionally substituted with one or two substituents independently selected from halogen and C_1-6A group of alkyl groups;

each R¹¹Independently selected from H, halogen, C_1-6Alkyl and C_1-6A haloalkyl group;

R¹²is C_1-6An alkyl group;

n is 0, 1, 2, 3 or 4; and

p is 0, 1 or 2.

One aspect is a compound having the structure of formula (I), or a pharmaceutically acceptable salt or solvate thereof:

wherein:

is a 9-membered bicyclic heteroaryl ring;

x, Y and Z are selected from ═ C (R)¹¹) -and-N-wherein at least two of X, Y and Z are ═ C (R)¹¹)-；

R³is-N (H) C (O) OR⁵、-OC(O)NR⁶R⁷、-N(H)C(O)NR⁶R⁷or-N (H) C (O) R⁸；

Each R⁴Independently selected from halogen, -CN, -OR⁹、-SR⁹、-N(R¹⁰)₂、-S(O)R⁹、-S(O)₂R⁹、-NHS(O)₂R⁹、-S(O)₂N(R¹⁰)₂、-C(O)R⁹、-C(O)OR⁹、-OC(O)R⁹、-C(O)N(R¹⁰)₂、-OC(O)N(R¹⁰)₂、-NR¹⁰C(O)N(R¹⁰)₂、-NR¹⁰C(O)R⁹、-NR¹⁰C(O)OR⁹Optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted phenyl and optionally substituted heteroaryl;

R⁵selected from the group consisting of optionally substituted alkyl, optionally substituted heterocycloalkyl, optionally substituted phenyl, and optionally substituted heteroaryl;

R⁸Selected from optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted phenyl, optionally substituted heterocycloalkyl, and optionally substituted heteroaryl;

each R⁹Independently selected from optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted phenyl and optionally substituted heteroaryl;

each R¹¹Independently selected from H, halogen and optionally substituted alkyl;

n is 0, 1, 2, 3 or 4; and

p is 0, 1 or 2.

Another aspect is a compound having the structure of formula (II), or a pharmaceutically acceptable salt or solvate thereof:

wherein:

is a 9-membered bicyclic heteroaryl ring;

x, Y and Z are selected from ═ C (R)¹¹) -and ═ N-, where X, Y and Z areIs ═ C (R)¹¹)-；

R³selected from-N (H) C (O) OR⁵、-OC(O)NR⁶R⁷、-N(H)C(O)NR⁶R⁷and-N (H) C (O) R⁸；

Each R⁴Independently selected from halogen, -CN, -OR⁹、-SR⁹、-N(R¹⁰)₂、-S(O)R⁹、-S(O)₂R⁹、-NHS(O)₂R⁹、-S(O)₂N(R¹⁰)₂、-C(O)R⁹、-C(O)OR⁹、-OC(O)R⁹、-C(O)N(R¹⁰)₂、-OC(O)N(R¹⁰)₂、-NR¹⁰C(O)N(R¹⁰)₂、-NR¹⁰C(O)R⁹、-NR¹⁰C(O)OR⁹、C_1-10Alkyl radical, C_1-10alkyl-OH, C _1-10alkyl-OR⁹、C_2-10Alkenyl radical, C_2-10Alkynyl, C_1-10Haloalkyl, C_1-10haloalkyl-OH, C_2-10Haloalkenyl, C_3-12Cycloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl, -C_2-6alkenyl-C_3-12Cycloalkyl, phenyl, -C_1-6Alkyl-phenyl, -C_2-6Alkenyl-phenyl, C_2-9Heterocycloalkyl and C_2-9Heteroaryl, in which phenyl, -C_1-6Alkyl-phenyl, -C_2-6Alkenyl-phenyl, C_2-9Heterocycloalkyl and C_2-9Heteroaryl is optionally substituted with one, two or three independently selected from halogen and C_1-6A group of alkyl groups;

R⁵is selected from C_1-6Alkyl, -C_1-6alkyl-OH, -C_1-6alkyl-O-C_1-6Alkyl, -C_1-6alkyl-O-C (O) C_1-6Alkyl radical、C_2-9Heterocycloalkyl, -C_1-6alkyl-C_2-9Heterocycloalkyl, phenyl, -C_1-6Alkyl-phenyl and C_2-9Heteroaryl group, wherein C_2-9Heterocycloalkyl, -C_1-6alkyl-C_2-9Heterocycloalkyl, phenyl, -C_1-6Alkyl-phenyl and C_2-9Heteroaryl is optionally substituted with one or two substituents independently selected from halogen and C_1-6A group of alkyl groups;

R⁸is selected from C_1-6Alkyl radical, C_1-6Haloalkyl, -C_1-6alkyl-OH, -C_1-6alkyl-O-C _1-6Alkyl radical, C_3-6Cycloalkyl, phenyl, C_2-9Heterocycloalkyl and C_2-9Heteroaryl group, wherein C_3-6Cycloalkyl, phenyl, C_2-9Heterocycloalkyl and C_2-9Heteroaryl is optionally substituted with one or two substituents independently selected from halogen and C_1-6A group of alkyl groups;

each R⁹Independently selected from C_1-10Alkyl radical, C_1-10Haloalkyl, C_3-12Cycloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl, phenyl, -C_1-6Alkyl-phenyl and C_2-9Heteroaryl, in which phenyl, -C_1-6Alkyl-phenyl and C_2-9Heteroaryl is optionally substituted with one or two substituents independently selected from halogen and C_1-6A group of alkyl groups;

each R¹⁰Independently selected from H, C_1-10Alkyl radical, C_1-10Haloalkyl, C_3-12Cycloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl, phenyl, -C_1-6Alkyl-phenyl and C_2-9Heteroaryl, in which phenyl, -C_1-6Alkyl-phenyl andC_2-9heteroaryl is optionally substituted with one or two substituents independently selected from halogen and C_1-6A group of alkyl groups;

each R¹¹Independently selected from H, halogen, C_1-6Alkyl and C_1-6A haloalkyl group;

n is 0, 1, 2, 3 or 4; and

p is 0, 1 or 2.

Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R¹And R²Independently selected from H and C_1-6An alkyl group. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹And R²Each is H. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R¹And R²Each is C_1-6An alkyl group. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R¹And R²Each is-CH₃. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R¹And R²Together with the nitrogen to which they are attached form a 3-, 4-, 5-or 6-membered heterocycloalkyl ring, optionally substituted with one or two substituents independently selected from halogen and C_1-6The radical of an alkyl group. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R¹And R²Together with the nitrogen to which they are attached form an unsubstituted 3-, 4-, 5-, or 6-membered heterocycloalkyl ring. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R⁵Is selected from C_1-6Alkyl, -C_1-6alkyl-OH, C_1-6alkyl-O-C_1-6Alkyl radical, C _1-6alkyl-O-C (O) C_1-6Alkyl radical, C_2-9Heterocycloalkyl, -C_1-6alkyl-C_2-9Heterocycloalkyl, -C_1-6Alkyl-phenyl and C_2-9A heteroaryl group. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R⁵Is selected from C_1-6Alkyl, -C_1-6alkyl-OH, -C_1-6alkyl-O-C_1-6Alkyl, -C_1-6alkyl-C_2-9Heterocycloalkyl and-C_1-6Alkyl-phenyl. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R⁵Is C_1-6An alkyl group. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R⁵is-CH₃. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R⁵is-C_1-6alkyl-OH. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R⁵is-C_1-6alkyl-O-C_1-6An alkyl group. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R⁵is-C_1-6alkyl-C_2-9A heterocycloalkyl group. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ⁵is-C_1-6Alkyl-phenyl. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R⁵is-CH₂-phenyl. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-OC (O) NR⁶R⁷. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) NR⁶R⁷. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R⁶And R⁷Independently selected from H, C_1-6Alkyl, -C_1-6alkyl-OH, -C_1-6alkyl-O-C_1-6Alkyl and-C_1-6alkyl-N (C)_1-6Alkyl radical)₂. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R⁶And R⁷Independently selected from H, C_1-6Alkyl, -C_1-6alkyl-O-C_1-6Alkyl and-C_1-6alkyl-N (C)_1-6Alkyl radical)₂. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R⁶And R⁷Independently selected from C_1-6An alkyl group. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ⁶And R⁷Each is-CH₃. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) R⁸. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R⁸is-C_1-6alkyl-OH. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R⁸is-C_1-6alkyl-O-C_1-6An alkyl group. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R⁸Is optionally substituted with one or two independently selected from halogen and C_1-6Phenyl of the radical of alkyl. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R⁸Is optionally substituted with one or two independently selected from halogen and C_1-6C of the radical of an alkyl group_2-9A heteroaryl group. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, -OR⁹、-C(O)OR⁹、-C(O)-C_1-10Alkyl radical, C_1-10Alkyl radical, C_1-10alkyl-OH, C_2-10Alkenyl radical, C_1-10Haloalkyl, C_1-10haloalkyl-OH, C _2-10Haloalkenyl, C_3-12Cycloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl, phenyl and-C_1-6Alkyl-phenyl, wherein phenyl and-C_1-6Alkyl-phenyl optionally substituted with one, two or three independently selected from halogen and C_1-6The radical of an alkyl group. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, -OR⁹、-C(O)OR⁹、C_1-10Alkyl radical, C_1-10alkyl-OH, C_1-10Haloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl and-C_1-6Alkyl-phenyl of which-C_1-6Alkyl-phenyl is optionally substituted with one or two halogens. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁹Independently selected from C_1-10Alkyl radical, C_1-10Haloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl, phenyl and-C_1-6Alkyl-phenyl, wherein phenyl and-C_1-6Alkyl-phenyl optionally substituted with one or two independently selected from halogen and C_1-6The radical of an alkyl group. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, whereinSelected from: some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, whereinSelected from: Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R⁴Is C_1-10An alkyl group. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ⁴Is C_1-10A haloalkyl group. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R⁴is-OR⁹. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R⁴is-OR⁹And R is⁹is-C optionally substituted with one or two halogens_1-6Alkyl-phenyl. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, whereinSelected from: some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen and C_1-10An alkyl group. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein p is 0. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein p is 1. Some embodiments are compounds of formula (Q), (I) or (II), or a pharmaceutically acceptable salt or solvate thereof Wherein p is 2. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein X, Y and Z are each ═ C (R)¹¹) -. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein X is ═ N-, Y is ═ C (R)¹¹) -, and Z is ═ C (R)¹¹) -. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein X is ═ C (R)¹¹) -, Y is ═ C (R)¹¹) -, and Z is ═ N-. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein X is ═ C (R)¹¹) -, Y is ═ N-, and Z is ═ C (R)¹¹) -. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is¹¹Is H. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein X is ═ c (h) -, Y is ═ c (h) -, and Z is ═ c (cl) -. Some embodiments are compounds of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein X is ═ C (h) -, Y is ═ C (h) -, and Z is ═ C (CH) ₃)-。

Another aspect described herein is a pharmaceutical composition comprising a compound of formula (Q), (I) or (II), or a pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable excipient.

Another aspect is a method of treating a disease or condition mediated by transglutaminase 2 in a patient in need of such treatment, said method comprising administering to the patient a therapeutically effective amount of a compound of formula (Q), (I) or (II), or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable excipient.

Another aspect of the invention relates to a method of treating a disease or disorder mediated by transglutaminase 2 in a patient in need of such treatment, wherein the disease or disorder is celiac disease, a neurodegenerative disease, an ocular disease, cancer, or fibrosis.

Another aspect is a method of treating cancer in a patient in need of such treatment, said method comprising administering to the patient a therapeutically effective amount of a compound of formula (Q), (I) or (II), or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition comprising a compound of formula (Q), (I) or (II), or a pharmaceutically acceptable salt or solvate thereof.

Also described herein is a method of treating celiac disease in a patient in need of such treatment, which comprises administering to the patient a therapeutically effective amount of a compound of formula (Q), (I) or (II), or a pharmaceutically acceptable salt or solvate thereof. Some embodiments are methods of treating renal fibrosis in a patient in need of such treatment, comprising administering to the patient a therapeutically effective amount of a compound of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof.

Also described herein is a method of treating a neurodegenerative disease in a patient in need of such treatment, the method comprising administering to the patient a therapeutically effective amount of a compound of formula (Q), (I) or (II), or a pharmaceutically acceptable salt or solvate thereof. Some embodiments are methods of treating a neurodegenerative disease in a patient in need of such treatment, comprising administering to the patient a therapeutically effective amount of a compound of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein the neurodegenerative disease is selected from: parkinson's disease, Huntington's disease and Alzheimer's disease.

Some embodiments are methods of treating an ocular disorder in a patient in need of such treatment, comprising administering to the patient a therapeutically effective amount of a compound of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof. Some embodiments are methods of treating an ocular disease in a patient in need of such treatment, comprising administering to the patient a therapeutically effective amount of a compound of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein the ocular disease is selected from the group consisting of macular degeneration, glaucoma, cataracts, and uveitis.

Some embodiments are methods of treating cancer in a patient in need of such treatment, comprising administering to the patient a therapeutically effective amount of a compound of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof. Some embodiments are methods of treating cancer in a patient in need of such treatment, comprising administering to the patient a therapeutically effective amount of a compound of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, wherein the cancer is selected from: melanoma, glioblastoma, meningioma, pancreatic cancer, renal cell carcinoma, and breast cancer.

Some embodiments are methods of treating renal fibrosis in a patient in need of such treatment, comprising administering to the patient a therapeutically effective amount of a compound of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof.

Some embodiments are methods of treating idiopathic pulmonary fibrosis in a patient in need of such treatment, comprising administering to the patient a therapeutically effective amount of a compound of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof.

Some embodiments are methods of treating liver fibrosis in a patient in need of such treatment, comprising administering to the patient a therapeutically effective amount of a compound of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof.

Also described herein are methods of reducing transglutaminase 2(TG2) activity in a subject, comprising administering to the subject a compound of formula (Q), (I) or (II), or a pharmaceutically acceptable salt or solvate thereof, in a dose effective to reduce TG2 activity.

Another aspect is a compound of formula (Q), (I) or (II), or a pharmaceutically acceptable salt thereof, for use in therapy.

Another aspect is a compound of formula (Q), (I) or (II), or a pharmaceutically acceptable salt or solvate thereof, for use in the treatment of celiac disease, neurodegenerative disease, ocular disease, cancer or fibrosis.

Another aspect is a compound of formula (Q), (I) or (II), or a pharmaceutically acceptable salt or solvate thereof, for use in the treatment of celiac disease.

Another aspect is a compound of formula (Q), (I) or (II), or a pharmaceutically acceptable salt or solvate thereof, for use in the treatment of a neurodegenerative disease.

Another aspect is a compound of formula (Q), (I) or (II), or a pharmaceutically acceptable salt or solvate thereof, for use in the treatment of a neurodegenerative disease, wherein the neurodegenerative disease is selected from: parkinson's disease, Huntington's disease and Alzheimer's disease.

Another aspect is a compound of formula (Q), (I) or (II), or a pharmaceutically acceptable salt or solvate thereof, for use in the treatment of an ocular disease.

Another aspect is a compound of formula (Q), (I) or (II), or a pharmaceutically acceptable salt or solvate thereof, for use in treating an ocular disease, wherein the ocular disease is selected from: macular degeneration, glaucoma, cataracts, and uveitis.

Another aspect is a compound of formula (Q), (I) or (II), or a pharmaceutically acceptable salt or solvate thereof, for use in the treatment of cancer.

Another aspect is a compound of formula (Q), (I) or (II), or a pharmaceutically acceptable salt or solvate thereof, for use in treating cancer, wherein the cancer is selected from: melanoma, glioblastoma, meningioma, pancreatic cancer, renal cell carcinoma, and breast cancer.

Another aspect is a compound of formula (Q), (I) or (II), or a pharmaceutically acceptable salt or solvate thereof, for use in treating fibrosis.

Another aspect is a compound of formula (Q), (I) or (II), or a pharmaceutically acceptable salt or solvate thereof, for use in treating renal fibrosis.

Another aspect is a compound of formula (Q), (I) or (II), or a pharmaceutically acceptable salt or solvate thereof, for use in the treatment of idiopathic pulmonary fibrosis.

Another aspect is a compound of formula (Q), (I) or (II), or a pharmaceutically acceptable salt or solvate thereof, for use in treating liver fibrosis.

Another aspect is a compound of formula (Q), (I) or (II), or a pharmaceutically acceptable salt or solvate thereof, for use in reducing transglutaminase 2(TG2) activity.

In another aspect, there is provided the use of a compound of formula (Q), (I) or (II), or a pharmaceutically acceptable salt or solvate thereof, in the manufacture of a medicament for the treatment of a disease or condition mediated by transglutaminase 2(TG 2).

Some embodiments is the use of a compound of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, in the manufacture of a medicament for treating a disease or disorder mediated by transglutaminase 2, wherein the disease or disorder is celiac disease, a neurodegenerative disease, an ocular disease, cancer, or fibrosis.

Some embodiments are the use of a compound of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, in the manufacture of a medicament for the treatment of celiac disease. Some embodiments are the use of a compound of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, in the manufacture of a medicament for the treatment of a neurodegenerative disease. Some embodiments are the use of a compound of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, in the manufacture of a medicament for the treatment of an ocular disease. Some embodiments are the use of a compound of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, in the manufacture of a medicament for the treatment of cancer. Some embodiments is the use of a compound of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, in the manufacture of a medicament for the treatment of fibrosis. Some embodiments are the use of a compound of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, in the manufacture of a medicament for the treatment of renal fibrosis. Some embodiments is the use of a compound of formula (Q), (I) or (II), or a pharmaceutically acceptable salt or solvate thereof, in the manufacture of a medicament for the treatment of idiopathic pulmonary fibrosis. Some embodiments is the use of a compound of formula (Q), (I), or (II), or a pharmaceutically acceptable salt or solvate thereof, in the manufacture of a medicament for treating liver fibrosis.

Detailed Description

Definition of

As used herein and in the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "an agent" includes a plurality of such agents, and reference to "a cell" includes reference to one or more cells (or a plurality of cells) and equivalents thereof. When ranges are used herein for physical properties, such as molecular weight, or chemical properties, such as chemical formulas, all combinations and subcombinations of ranges and specific embodiments therein are intended to be included. When referring to a number or numerical range, the term "about" means that the number or numerical range recited is an approximation within experimental variability (or within statistical experimental error), and thus, the number or numerical range varies from 1% to 15% of the number or numerical range recited. The term "comprising" (and related terms such as "comprising" or "including" or "having" or "including") is not intended to exclude those that may "consist of … …" or "consist essentially of … …" described features in other certain embodiments (e.g., embodiments of any of the compositions, methods, processes, etc., of matter described herein).

As used in the specification and the appended claims, the following terms have the meanings indicated below, unless specified to the contrary.

As used herein, C₁-C_xComprising C₁-C₂、C₁-C₃...C₁-C_x。C₁-C_xRefers to the number of carbon atoms (excluding optional substituents) that make up the indicated portion thereof.

"amino" means-NH₂A group.

"cyano" refers to the group-CN.

"nitro" means-NO₂A group.

"oxa" refers to an-O-group.

"oxo" refers to an ═ O group.

"thio" refers to ═ S groups.

"imino" refers to an ═ N-H group.

"oximino" refers to the group ═ N-OH.

"alkyl" or "alkylene" isRefers to a straight or branched hydrocarbon chain radical consisting only of carbon and hydrogen atoms, which is free of unsaturation and has from 1 to 15 carbon atoms (e.g. C)₁-C₁₅Alkyl groups). In certain embodiments, the alkyl group contains 1 to 13 carbon atoms (e.g., C)₁-C₁₃Alkyl groups). In certain embodiments, the alkyl group contains 1 to 10 carbon atoms (e.g., C)₁-C₁₀Alkyl groups). In certain embodiments, the alkyl group contains 1 to 8 carbon atoms (e.g., C)₁-C₈Alkyl groups). In other embodiments, the alkyl group contains 1 to 6 carbon atoms (e.g., C)₁-C₆Alkyl groups). In other embodiments, the alkyl group contains 1 to 5 carbon atoms (e.g., C)₁-C₅Alkyl groups). In other embodiments, the alkyl group contains 1 to 4 carbon atoms (e.g., C) ₁-C₄Alkyl groups). In other embodiments, the alkyl group contains 1 to 3 carbon atoms (e.g., C)₁-C₃Alkyl groups). In other embodiments, the alkyl group contains 1 to 2 carbon atoms (e.g., C)₁-C₂Alkyl groups). In other embodiments, the alkyl group contains 1 carbon atom (e.g., C)₁Alkyl groups). In other embodiments, the alkyl group contains 5 to 15 carbon atoms (e.g., C)₅-C₁₅Alkyl groups). In other embodiments, the alkyl group contains 5 to 8 carbon atoms (e.g., C)₅-C₈Alkyl groups). In other embodiments, the alkyl group contains 2 to 5 carbon atoms (e.g., C)₂-C₅Alkyl groups). In other embodiments, the alkyl group contains 3 to 5 carbon atoms (e.g., C)₃-C₅Alkyl groups). In other embodiments, the alkyl group is selected from: methyl, ethyl, 1-propyl (n-propyl), 1-methylethyl (isopropyl), 1-butyl (n-butyl), 1-methylpropyl (sec-butyl), 2-methylpropyl (isobutyl), 1-dimethylethyl (tert-butyl) and 1-pentyl (n-pentyl). The alkyl group is connected to the rest of the molecule by a single bond. Unless stated otherwise specifically in the specification, an alkyl group is optionally substituted with one or more of the following substituents: halogen, cyano, nitro, oxo, thio, imino, hydroxyimino, trimethylsilyl, -OR ^a、-SR^a、-OC(O)R^a、-N(R^a)₂、-C(O)R^a、-C(O)OR^a、-C(O)N(R^a)₂、-N(R^a)C(O)OR^f、-OC(O)-NR^aR^f、-N(R^a)C(O)R^f、-N(R^a)S(O)_tR^f(wherein t is 1 or 2), -S (O)_tOR^a(wherein t is 1 or 2), -S (O)_tR^f(wherein t is 1 or 2) and-S (O)_tN(R^a)₂(wherein t is 1 or 2) wherein each R^aIndependently hydrogen, alkyl, fluoroalkyl, cycloalkyl, aryl, aralkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl, and each R^fIndependently an alkyl, fluoroalkyl, cycloalkyl, aryl, aralkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl group.

"alkoxy" refers to a group bonded through an oxygen atom of the formula-O-alkyl, wherein alkyl is an alkyl chain as defined above.

"alkenyl" means a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon double bond and having from 2 to 12 carbon atoms. In other embodiments, alkenyl groups contain 2 to 10 carbon atoms. In certain embodiments, alkenyl groups contain 2 to 8 carbon atoms. In other embodiments, alkenyl groups contain 2 to 6 carbon atoms. In other embodiments, alkenyl groups contain 2 to 4 carbon atoms. The alkenyl group is attached to the remainder of the molecule by a single bond, such as vinyl (i.e., vinyl), prop-1-enyl (i.e., allyl), but-1-enyl, pent-1, 4-dienyl, and the like. Unless stated otherwise specifically in the specification, an alkenyl group is optionally substituted with one or more of the following substituents: halogen, cyano, nitro, oxo, thio, imino, hydroxyimino, trimethylsilyl, -OR ^a、-SR^a、-OC(O)-R^f、-N(R^a)₂、-C(O)R^a、-C(O)OR^a、-C(O)N(R^a)₂、-N(R^a)C(O)OR^f、-OC(O)-nR^aR^f、-N(R^a)C(O)R^f、-N(R^a)S(O)_tR^f(wherein t is 1 or 2), -S (O)_tOR^a(wherein t is 1 or 2), -S (O)_tR^f(wherein t is 1 or 2) and-S (O)_tN(R^a)₂(wherein t is 1 or 2) wherein each R^aIndependently hydrogen, alkyl, fluoroalkyl, cycloalkyl, aryl, aralkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl, and each R^fIndependently an alkyl, fluoroalkyl, cycloalkyl, aryl, aralkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl group.

"alkynyl" means a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing at least one carbon-carbon triple bond and having from 2 to 12 carbon atoms. In certain embodiments, alkynyl groups contain 2 to 10 carbon atoms. In certain embodiments, alkynyl groups contain 2 to 8 carbon atoms. In other embodiments, alkynyl groups have 2 to 4 carbon atoms. The alkynyl group is attached to the remainder of the molecule by a single bond, for example ethynyl, propynyl, butynyl, pentynyl, hexynyl, and the like. Unless stated otherwise specifically in the specification, alkynyl groups are optionally substituted with one or more of the following substituents: halogen, cyano, nitro, oxo, thio, imino, hydroxyimino, trimethylsilyl, -OR^a、-SR^a、-OC(O)R^a、-N(R^a)₂、-C(O)R^a、-C(O)OR^a、-C(O)N(R^a)₂、-N(R^a)C(O)OR^f、-OC(O)-NR^aR^f、-N(R^a)C(O)R^f、-N(R^a)S(O)_tR^f(wherein t is 1 or 2), -S (O) _tOR^a(wherein t is 1 or 2), -S (O)_tR^f(wherein t is 1 or 2) and-S (O)_tN(R^a)₂(wherein t is 1 or 2) wherein each R^aIndependently hydrogen, alkyl, fluoroalkyl, cycloalkyl, aryl, aralkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl, and each R^fIndependently an alkyl, fluoroalkyl, cycloalkyl, aryl, aralkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl group.

"aryl" refers to a group derived from an aromatic monocyclic or polycyclic hydrocarbon ring system by the removal of a hydrogen atom from a ring carbon atom. Aromatic monocyclic or polycyclic hydrocarbon ring systems containing only hydrogen and 6 to 18 carbonsCarbon of an atom, wherein at least one ring of the ring system is completely unsaturated, i.e. according to Huckel theory it comprises a cyclic, delocalized (4n +2) pi-electron system. Ring systems derivatized to form aryl groups include, but are not limited to, groups such as benzene, fluorene, indane, indene, tetralin, and naphthalene. Unless otherwise specifically stated in the specification, the term "aryl" or the prefix "ar-" (for example in "aralkyl") is intended to include aryl groups optionally substituted with one or more substituents independently selected from: alkyl, alkenyl, alkynyl, halogen, fluoroalkyl, cyano, nitro, aryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, heterocycloalkyl, heteroaryl, heteroarylalkyl, -R ^b-OR^a、-R^b-OC(O)-R^a、-R^b-OC(O)-OR^a、-R^b-OC(O)-N(R^a)₂、-R^b-N(R^a)₂、-R^b-C(O)R^a、-R^b-C(O)OR^a、-R^b-C(O)N(R^a)₂、-R^b-O-R^c-C(O)N(R^a)₂、-R^b-N(R^a)C(O)OR^a、-R^b-N(R^a)C(O)R^a、-R^b-N(R^a)S(O)_tR^a(wherein t is 1 or 2), -R^b-S(O)_tOR^a(wherein t is 1 or 2), -R^b-S(O)_tR^a(wherein t is 1 or 2) and-R^b-S(O)_tN(R^a)₂(wherein t is 1 or 2) wherein each R^aIndependently hydrogen, alkyl, fluoroalkyl, cycloalkyl, cycloalkylalkyl, aryl (optionally substituted with one or more halo groups), aralkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl, each R^bIndependently is a direct bond or a linear or branched alkylene or alkenylene chain, and R^cIs a linear or branched alkylene or alkenylene chain.

"aryloxy" refers to a group bonded through an oxygen atom of the formula-O-aryl, wherein aryl is as defined above.

"aralkyl" means a group of the formula-R^c-a radical of an aryl radical, wherein R^cIs an alkylene chain as defined above, e.g.Methylene, ethylene, and the like. The alkylene chain portion of the aralkyl group is optionally substituted as described above for the alkylene chain. The aryl portion of the aralkyl group is optionally substituted as described above for aryl.

"aralkoxy" means a group bonded through an oxygen atom of the formula-O-aralkyl, where aralkyl is as defined above.

"aralkenyl" means a group of formula-R^d-a radical of an aryl radical, wherein R^dIs an alkenylene chain as defined above. The aryl moiety of the aralkenyl is optionally substituted as described above for aryl. The alkenylene chain portion of the aralkenyl group is optionally substituted as described above for alkenylene.

"aralkynyl" means the formula-R^e-a radical of an aryl radical, wherein R^eIs an alkynylene chain as defined above. The aryl moiety of the aralkynyl is optionally substituted as described above for aryl. The alkynylene moiety of the aralkynyl is optionally substituted as described above for the alkynylene chain.

"cycloalkyl" refers to a stable, non-aromatic, monocyclic or polycyclic hydrocarbon radical consisting solely of carbon and hydrogen atoms, including fused or bridged ring systems having from 3 to 15 carbon atoms. In certain embodiments, cycloalkyl groups contain 3 to 10 carbon atoms. In other embodiments, the cycloalkyl group contains 5 to 7 carbon atoms. The cycloalkyl group is connected to the rest of the molecule by a single bond. Cycloalkyl groups are saturated (i.e., contain only a single C-C bond) or partially unsaturated (i.e., contain one or more double or triple bonds). Examples of monocyclic cycloalkyl groups include, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. In certain embodiments, cycloalkyl contains 3 to 8 carbon atoms (e.g., C)₃-C₈Cycloalkyl groups). In other embodiments, the cycloalkyl group contains 3 to 7 carbon atoms (e.g., C)₃-C₇Cycloalkyl groups). In other embodiments, the cycloalkyl group contains 3 to 6 carbon atoms (e.g., C)₃-C₆Cycloalkyl groups). In other embodiments, the cycloalkyl group contains 3 to 5 carbon atoms (e.g., C) ₃-C₅Cycloalkyl groups). In other embodiments, the cycloalkyl group contains 3 to 4 carbon atoms (e.g., C)₃-C₄Cycloalkyl groups). Is partially provided withSaturated cycloalkyl groups are also known as "cycloalkenyl". Examples of monocyclic cycloalkenyl groups include, for example, cyclopentenyl, cyclohexenyl, cycloheptenyl, and cyclooctenyl. Polycyclic cycloalkyl groups include, for example, adamantyl, norbornyl (i.e., bicyclo [ 2.2.1)]Heptyl), norbornenyl, decalinyl, 7-dimethyl-bicyclo [2.2.1]Heptyl, and the like. Unless otherwise specifically stated in the specification, the term "cycloalkyl" is intended to include cycloalkyl optionally substituted with one or more substituents independently selected from: alkyl, alkenyl, alkynyl, halogen, fluoroalkyl, cyano, nitro, aryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, heterocycloalkyl, heteroaryl, heteroarylalkyl, -R^b-OR^a、-R^b-OC(O)-R^a、-R^b-OC(O)-OR^a、-R^b-OC(O)-N(R^a)₂、-R^b-N(R^a)₂、-R^b-C(O)R^a、-R^b-C(O)OR^a、-R^b-C(O)N(R^a)₂、-R^b-O-R^c-C(O)N(R^a)₂、-R^b-N(R^a)C(O)OR^a、-R^b-N(R^a)C(O)R^a、-R^b-N(R^a)S(O)_tR^a(wherein t is 1 or 2), -R^b-S(O)_tOR^a(wherein t is 1 or 2), -R^b-S(O)_tR^a(wherein t is 1 or 2) and-R^b-S(O)_tN(R^a)₂(wherein t is 1 or 2) wherein each R^aIndependently hydrogen, alkyl, fluoroalkyl, cycloalkyl, cycloalkylalkyl, aryl (optionally substituted with one or more halo groups), aralkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl, each R ^bIndependently is a direct bond or a linear or branched alkylene or alkenylene chain, and R^cIs a linear or branched alkylene or alkenylene chain.

"halo" or "halogen" refers to a bromo, chloro, fluoro, or iodo substituent.

"haloalkyl" refers to an alkyl group as defined above substituted with one or more halo groups as defined above.

"fluoroalkyl" refers to an alkyl group as defined above substituted with one or more fluoro groups as defined above, for example trifluoromethyl, difluoromethyl, fluoromethyl, 2,2, 2-trifluoroethyl, 1-fluoromethyl-2-fluoroethyl, and the like. The alkyl portion of the fluoroalkyl group is optionally substituted as described above for alkyl.

"haloalkoxy" means an alkoxy group as defined above substituted with one or more halo groups as defined above.

"heterocycloalkyl" refers to a stable 3-to 18-membered non-aromatic cyclic group containing 2 to 12 carbon atoms and 1 to 6 heteroatoms selected from nitrogen, oxygen, and sulfur. Unless otherwise specifically stated in the specification, the heterocycloalkyl group is a monocyclic, bicyclic, tricyclic or tetracyclic ring system, which includes fused, spiro or bridged ring systems. The heteroatoms in the heterocycloalkyl group are optionally oxidized. If one or more nitrogen atoms are present, they are optionally quaternized. The heterocycloalkyl group is partially or fully saturated. In some embodiments, the heterocycloalkyl group is attached to the rest of the molecule through any atom of the ring. Examples of such heterocycloalkyl groups include, but are not limited to, dioxolanyl, thienyl [1,3 ] ]Dithiacyclohexyl, decahydroisoquinolinyl, imidazolinyl, imidazolidinyl, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, oxazolidinyl, piperidinyl, piperazinyl, 4-piperidinonyl, pyrrolidinyl, pyrazolidinyl, quinuclidinyl, thiazolidinyl, tetrahydrofuranyl, trithianyl, tetrahydropyranyl, thiomorpholinyl (thiomorpholinyl), 1-oxo-thiomorpholinyl, and 1, 1-dioxo-thiomorpholinyl. Unless otherwise specifically stated in the specification, the term "heterocycloalkyl" is intended to include heterocycloalkyl as defined above optionally substituted with one or more substituents selected from: alkyl, alkenyl, alkynyl, halogen, fluoroalkyl, oxo, thio, cyano, nitro, aryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, heterocycloalkyl, heteroaryl, heteroarylalkyl, -R^b-OR^a、-R^b-OC(O)-R^a、-R^b-OC(O)-OR^a、-R^b-OC(O)-N(R^a)₂、-R^b-N(R^a)₂、-R^b-C(O)R^a、-R^b-C(O)OR^a、-R^b-C(O)N(R^a)₂、-R^b-O-R^c-C(O)N(R^a)₂、-R^b-N(R^a)C(O)OR^a、-R^b-N(R^a)C(O)R^a、-R^b-N(R^a)S(O)_tR^a(wherein t is 1 or 2), -R^b-S(O)_tOR^a(wherein t is 1 or 2), -R^b-S(O)_tR^a(wherein t is 1 or 2) and-R^b-S(O)_tN(R^a)₂(wherein t is 1 or 2) wherein each R^aIndependently hydrogen, alkyl, fluoroalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl, each R ^bIndependently is a direct bond or a linear or branched alkylene or alkenylene chain, and R^cIs a linear or branched alkylene or alkenylene chain.

"heteroaryl" refers to a group derived from a 5-to 18-membered aromatic cyclic group containing 1 to 17 carbon atoms and 1 to 6 heteroatoms selected from nitrogen, oxygen, and sulfur. As used herein, the heteroaryl group is a monocyclic, bicyclic, tricyclic or tetracyclic ring system, wherein at least one ring in the ring system is fully unsaturated, i.e. according to huckel theory it comprises a cyclic, delocalized (4n +2) pi-electron system. Heteroaryl includes fused or bridged ring systems. The heteroatoms in the heteroaryl group are optionally oxidized. If one or more nitrogen atoms are present, they are optionally quaternized. The heteroaryl group is attached to the rest of the molecule through any atom of the ring. Illustrative examples of heteroaryl groups for use in the present invention include, but are not limited to, furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, isothiazolyl, pyridyl, pyridazinyl, pyrazinyl, pyrimidinyl, triazinyl, benzofuranyl, isobenzofuranyl, 2, 3-dihydrobenzofuranyl, 1, 3-benzodioxolyl, dihydrobenzodioxinyl, benzothienyl, indolizinyl, indolyl, isoindolyl, indolyl, and mixtures thereof, Indolinyl, benzimidazolyl, dihydrobenzimidazolyl, benzoxazolyl, dihydrobenzoxazolyl, benzothiazolyl, benzisothiazolyl, dihydrobenzisothiazolyl, indazolyl, imidazopyridinyl, pyrazolopyridinyl, benzotriazolyl, triazolopyridinyl, purinyl, quinolinyl, tetrahydroquinolinyl, isoquinolinyl, tetrahydroisoquinolinyl, quinoxalinyl, cinnolinyl, phthalazinyl, quinazolinyl, 1, 5-naphthyridinyl, 1, 6-naphthyridinyl, 1, 7-naphthyridinyl, 1, 8-naphthyridinyl, and pteridinyl. Examples of 5-membered "heteroaryl" groups include furyl, thienyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiadiazolyl, and isothiazolyl. Examples of 6-membered "heteroaryl" include oxo-pyridyl, pyridazinyl, pyrazinyl and pyrimidinyl. Examples of 6, 6-fused "heteroaryl" groups include quinolinyl, isoquinolinyl, quinoxalinyl, cinnolinyl, phthalazinyl, quinazolinyl, 1, 5-naphthyridinyl, 1, 6-naphthyridinyl, 1, 7-naphthyridinyl, 1, 8-naphthyridinyl, and pteridinyl. Examples of 6, 5-fused "heteroaryl" groups include benzofuranyl, benzothienyl, benzimidazolyl, benzothiazolyl, indolizinyl, indolyl, isoindolyl, and indazolyl. Unless otherwise specifically stated in the specification, the term "heteroaryl" is intended to include heteroaryl as defined above optionally substituted with one or more substituents selected from: alkyl, alkenyl, alkynyl, halogen, haloalkyl, oxo, thio, cyano, nitro, aryl, aralkyl, aralkenyl, aralkynyl, cycloalkyl, heterocycloalkyl, heteroaryl, heteroarylalkyl, -R ^b-OR^a、-R^b-OC(O)-R^a、-R^b-OC(O)-OR^a、-R^b-OC(O)-N(R^a)₂、-R^b-N(R^a)₂、-R^b-C(O)R^a、-R^b-C(O)OR^a、-R^b-C(O)N(R^a)₂、-R^b-O-R^c-C(O)N(R^a)₂、-R^b-N(R^a)C(O)OR^a、-R^b-N(R^a)C(O)R^a、-R^b-N(R^a)S(O)_tR^a(whereint is 1 or 2), -R^b-S(O)_tOR^a(wherein t is 1 or 2), -R^b-S(O)_tR^a(wherein t is 1 or 2) and-R^b-S(O)_tN(R^a)₂(wherein t is 1 or 2) wherein each R^aIndependently hydrogen, alkyl, fluoroalkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, heterocycloalkyl, heteroaryl, or heteroarylalkyl, each R^bIndependently is a direct bond or a linear or branched alkylene or alkenylene chain, and R^cIs a linear or branched alkylene or alkenylene chain. As used herein, "9-membered bicyclic heteroaryl ring" means a group or moiety comprising an aromatic bicyclic group comprising 9 ring atoms, including at least one carbon atom and heteroatoms independently selected from nitrogen, oxygen, and sulfur. Illustrative examples of 9-membered bicyclic heteroaryl rings include, but are not limited to, benzimidazolyl, imidazopyridinyl, purinyl, indolyl, pyrrolopyridinyl, pyrrolopyrimidinyl, benzoxazolyl, benzothiazolyl, imidazopyrazinyl, imidazopyridazinyl, pyrrolopyrazinyl, pyrrolopyridazinyl, oxazolopyridinyl, oxazolopyrimidinyl, oxazolopyridazinyl, benzofuranyl, furopyridinyl, furopyrimidinyl, furopyrazinyl, furopyridazinyl, thiazolopyridinyl, thiazolopyrimidinyl, thiazolopyrazinyl, thiazolopyridazinyl, benzothiophenyl, thienopyridinyl, thienopyrimidinyl, thienopyrazinyl, thienopyridazinyl, indolizinyl, pyrrolotriazinyl, imidazotriazinyl, triazolopyridinyl, triazolopyridazinyl, triazolopyrimidinyl, and triazolopyrazinyl.

"N-heteroaryl" refers to a heteroaryl group, as defined above, that contains at least one nitrogen, and wherein the point of attachment of the heteroaryl group to the rest of the molecule is through the nitrogen atom in the heteroaryl group. The N-heteroaryl group is optionally substituted as described above for heteroaryl.

"C-heteroaryl" refers to a heteroaryl group as defined above, and wherein the point of attachment of the heteroaryl group to the rest of the molecule is through a carbon atom in the heteroaryl group. C-heteroaryl is optionally substituted as described above for heteroaryl.

"heteroaryloxy" refers to a group bonded through an oxygen atom of the formula-O-heteroaryl, wherein heteroaryl is as defined above.

"Heteroarylalkyl" means a compound of the formula-R^c-a radical of heteroaryl, wherein R^cIs an alkylene chain as defined above. If the heteroaryl is a nitrogen-containing heteroaryl, the heteroaryl is optionally attached to the alkyl at a nitrogen atom. The alkylene chain of the heteroarylalkyl group is optionally substituted as defined above for the alkylene chain. The heteroaryl portion of the heteroarylalkyl group is optionally substituted as defined above for heteroaryl.

"Heteroarylalkoxy" means a compound of the formula-O-R^c-an oxygen atom-bonded group of heteroaryl, wherein R^cIs an alkylene chain as defined above. If the heteroaryl is a nitrogen-containing heteroaryl, the heteroaryl is optionally attached to the alkyl at a nitrogen atom. The alkylene chain of the heteroarylalkoxy group is optionally substituted as defined above for the alkylene chain. The heteroaryl portion of the heteroarylalkoxy group is optionally substituted as defined above for heteroaryl.

"tautomer" refers to molecules in which a proton may be transferred from one atom of one molecule to another atom of the same molecule. In certain embodiments, the compounds provided herein exist in tautomeric forms. In the case of possible tautomerism, there will be a chemical equilibrium of the tautomers. The exact ratio of tautomers depends on several factors including physical state, temperature, solvent and pH. Some examples of tautomeric equilibrium include:

"optional" or "optionally" means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where the event or circumstance occurs and instances where it does not. The term "optionally substituted" or "substituted" means that the group referred to may be substituted by one or more additional groups which are individually and independently selected from: alkyl, cyclicAlkyl, aryl, heteroaryl, heterocycloalkyl, -OH, alkoxy, aryloxy, alkylthio, arylthio, alkylsulfoxide, arylsulfoxide, alkylsulfone, arylsulfone, -CN, alkyne, C₁-C₆Alkyl alkynes, halogens, acyl, acyloxy, -CO₂H、-CO₂Alkyl, nitro, haloalkyl, fluoroalkyl and amino groups including mono-and di-substituted amino groups (e.g. -NH) ₂、-NHR、-N(R)₂) And protected derivatives thereof. For example, the optional substituent may be L^sR^sWherein each L^sIndependently selected from the group consisting of a bond, -O-, -C (═ O) -, -S (═ O)₂-、-NH-、-NHC(O)-、-C(O)NH-、S(＝O)₂NH-、-NHS(＝O)₂、-OC(O)NH-、-NHC(O)O-、-(C₁-C₆Alkyl) -or- (C₂-C₆Alkenyl) -; and each R^sIndependently selected from: H. (C)₁-C₆Alkyl group), (C)₃-C₈Cycloalkyl), aryl, heteroaryl, and heterocycloalkyl.

The term "independently" means that when more than one substituent is selected from a plurality of possible substituents, those substituents may be the same or different. The alternative definitions of the various groups and substituents of formula (I) provided throughout the specification are intended to specifically describe each compound class disclosed herein as well as the groups of one or more compound classes, respectively. The scope of the present invention includes any combination of these group and substituent definitions.

"pharmaceutically acceptable salts" include acid addition salts and base addition salts. The pharmaceutically acceptable salts of any of the pyrazole compounds described herein are intended to encompass any and all pharmaceutically suitable salt forms. Preferred pharmaceutically acceptable salts of the compounds described herein are pharmaceutically acceptable acid addition salts and pharmaceutically acceptable base addition salts. As used herein, the term "pharmaceutically acceptable salt" refers to a salt that retains the desired biological activity of the subject compound and exhibits minimal undesirable toxicological effects. These pharmaceutically acceptable salts can be prepared in situ during the final isolation and purification of the compound or by separately reacting the purified compound in its free acid or free base form with a suitable base or acid, respectively.

"pharmaceutically acceptable acid addition salts" refers to those salts that retain the biological effectiveness and properties of the free base, which are not biologically or otherwise undesirable, and which are formed with inorganic acids such as hydrochloric, hydrobromic, sulfuric, nitric, phosphoric, hydroiodic, hydrofluoric, phosphorous, and the like. Also included are salts formed with organic acids such as aliphatic mono-and dicarboxylic acids, phenyl substituted alkanoic acids, hydroxyalkanoic acids, alkanedioic acids, aromatic acids, aliphatic and aromatic sulfonic acids, and the like, and include, for example, acetic acid, trifluoroacetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like. Thus, exemplary salts include sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogenphosphate, dihydrogenphosphate, metaphosphate, pyrophosphate, chloride, bromide, iodide, acetate, trifluoroacetate, propionate, caprylate, isobutyrate, oxalate, malonate, succinate, suberate, sebacate, fumarate, maleate, mandelate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, phthalate, benzenesulfonate, tosylate, phenylacetate, citrate, lactate, malate, tartrate, mesylate, and the like. Also contemplated are Salts of amino acids, such as arginine, gluconate, and galacturonate (see, e.g., Berge S.M. et al, "Pharmaceutical Salts," Journal of Pharmaceutical Science, 66: 1-19 (1997)). Acid addition salts of basic compounds are prepared by contacting the free base form with a sufficient amount of the desired acid to form the salt.

"pharmaceutically acceptable base addition salts" refers to those salts that retain the biological effectiveness and properties of the free acid, which are not biologically or otherwise undesirable. These salts are prepared by adding an inorganic or organic base to the free acid. In some embodiments, pharmaceutically acceptable base addition salts are formed with metals or amines, such as alkali and alkaline earth metals or organic amines. Salts derived from inorganic bases include, but are not limited to, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts, and the like. Salts derived from organic bases include, but are not limited to: salts of primary, secondary and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, diethanolamine, 2-dimethylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procaine, N-dibenzylethylenediamine, chloroprocaine, hydrabamine, choline, betaine, ethylenediamine, ethylenedianiline, N-methylglucamine, glucosamine, methylglucamine, theobromine, purine, piperazine, piperidine, N-ethylpiperidine, polyamine resins and the like. See Berge et al, supra.

As used herein, "treatment" or "treating" or "alleviating" or "ameliorating" are used interchangeably herein. These terms refer to methods of achieving a beneficial or desired result, including but not limited to a therapeutic benefit and/or a prophylactic benefit. By "therapeutic benefit" is meant eradication or amelioration of the underlying disease being treated. Moreover, therapeutic benefit is achieved by eradicating or ameliorating one or more physiological symptoms associated with the underlying disease, such that an improvement may be observed in the patient even though the patient is still suffering from the underlying disease. For prophylactic benefit, the composition is administered to a patient at risk of a particular disease, or to a patient reporting one or more physiological symptoms of a disease, even if the disease has not been diagnosed.

The term "therapeutically effective amount" refers to any amount that results in the treatment, cure, or amelioration of a disease, disorder, or amelioration of a side effect, or a decrease in the rate of progression of a disease or disorder, as compared to a corresponding subject that does not receive that amount. The term also includes within its scope an amount effective to enhance normal physiological function. For use in therapy, a therapeutically effective amount of a compound of formula (I) or formula (II) and salts thereof may be administered as the starting chemical. In addition, the active ingredient may be present in the form of a pharmaceutical composition.

The term "patient" refers to a human or an animal.

The term "individual" refers to a human or an animal.

Compound (I)

The compounds of formula (Q), (I), (II), (IIa), (IIb), (IIc), (IId) or (IIe) described herein are inhibitors of TG 2. In some embodiments, compounds of formula (Q), (I), (II), (IIa), (IIb), (IIc), (IId), or (IIe) described herein, as well as pharmaceutical compositions comprising these compounds, are used to treat celiac disease, neurodegenerative disease, ocular disease, cancer, or fibrotic disease.

Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof:

wherein:

is a 9-membered bicyclic heteroaryl ring;

x, Y and Z are selected from ═ C (R)¹¹) -and-N-wherein at least two of X, Y and Z are ═ C (R)¹¹)-；

R³is-N (H) C (O) OR⁵、-OC(O)NR⁶R⁷、-N(H)C(O)NR⁶R⁷or-N (H) C (O) R⁸；

Each R⁴Independently selected from halogen, -CN, -OR⁹、-SR⁹、-N(R¹⁰)₂、-S(O)R⁹、-S(O)₂R⁹、-NHS(O)₂R⁹、-S(O)₂N(R¹⁰)₂、-C(O)R⁹、-C(O)OR⁹、-OC(O)R⁹、-C(O)N(R¹⁰)₂、-OC(O)N(R¹⁰)₂、-NR¹⁰C(O)N(R¹⁰)₂、-NR¹⁰C(O)R⁹、-NR¹⁰C(O)OR⁹Optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted phenyl and optionally substituted heteroaryl;

R⁵selected from the group consisting of optionally substituted alkyl, optionally substituted heterocycloalkyl, optionally substituted phenyl, and optionally substituted heteroaryl;

R⁶And R⁷Independently selected from H and optionally substituted alkyl; or R⁶And R⁷Together with the nitrogen to which they are attached form an optionally substituted 5-or 6-membered heterocycloalkyl ring;

R⁸selected from optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted phenyl, optionally substituted heterocycloalkyl, and optionally substituted heteroaryl;

each R⁹Independently selected from optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted phenyl and optionally substituted heteroaryl;

each R¹¹Independently selected from H, halogen and optionally substituted alkyl;

n is 0, 1, 2, 3 or 4; and

p is 0, 1 or 2.

Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein X, Y and Z are each ═ C (R)¹¹) -. In some embodiments of the compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein X and Y are each ═ c (h) -; and Z is ═ C (CH) -, (CH)₃) -or ═ c (cl) -. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein X, Y and Z are each ═ c (h) -. Some embodiments are of the formula (A) I) A compound, or a pharmaceutically acceptable salt or solvate thereof, wherein X is ═ N-, and Y is ═ C (R)¹¹) -, and Z is ═ C (R)¹¹) -. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein X is ═ N-, Y is ═ c (h) -, and Z is ═ c (h) -. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein X is ═ C (R)¹¹) -, Y is ═ N-, and Z is ═ C (R)¹¹) -. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein X is ═ c (h) -, Y is ═ N-, and Z is ═ c (h) -. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein X is ═ C (R)¹¹) -, Y is ═ C (R)¹¹) -, and Z is ═ N-. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein X is ═ c (h) -, Y is ═ c (h) -, and Z is ═ N-.

Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R¹And R²Independently selected from H and C_1-6An alkyl group. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹And R²Each is H. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R¹And R²Each is C_1-6An alkyl group. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R¹And R²Each is-CH₃. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R¹And R²Together with the nitrogen to which they are attached form a 3-, 4-, 5-or 6-membered heterocycloalkyl ring, optionally substituted with one or two substituents independently selected from halogen and C_1-6The radical of an alkyl group. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R¹And R²Together with the nitrogen to which they are attached form an unsubstituted 3-, 4-, 5-, or 6-membered heterocycloalkyl ring. Some embodiments are compounds of formula (I)Or a pharmaceutically acceptable salt or solvate thereof, wherein R¹And R²Together with the nitrogen to which they are attached form an unsubstituted 3-membered heterocycloalkyl ring. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R¹And R²Together with the nitrogen to which they are attached form an unsubstituted 4-membered heterocycloalkyl ring. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹And R²Together with the nitrogen to which they are attached form an unsubstituted 5-membered heterocycloalkyl ring. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R¹And R²Together with the nitrogen to which they are attached form an unsubstituted 6-membered heterocycloalkyl ring.

Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵And R is⁵Is selected from C_1-6Alkyl, -C_1-6alkyl-OH, C_1-6alkyl-O-C_1-6Alkyl radical, C_1-6alkyl-O-C (O) C_1-6Alkyl radical, C_2-9Heterocycloalkyl, -C_1-6alkyl-C_2-9Heterocycloalkyl, -C_1-6Alkyl-phenyl and C_2-9A heteroaryl group. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵And R is⁵Is selected from C_1-6Alkyl, -C_1-6alkyl-OH, -C_1-6alkyl-O-C_1-6Alkyl, -C_1-6alkyl-C_2-9Heterocycloalkyl and-C_1-6Alkyl-phenyl. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵And R is⁵Is C_1-6An alkyl group. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R ³is-N (H) C (O) OR⁵And R is⁵is-CH₃. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵And R is⁵is-C_1-6alkyl-OH. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵And R is⁵is-C_1-6alkyl-O-C_1-6An alkyl group. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵And R is⁵is-C_1-6alkyl-C_2-9A heterocycloalkyl group. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵And R is⁵is-C_1-6Alkyl-phenyl. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵And R is⁵is-CH₂-phenyl. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-OC (O) NR⁶R⁷. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-OC (O) NR⁶R⁷And R is³is-N (H) C (O) NR⁶R⁷. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R ³is-OC (O) NR⁶R⁷And R is⁶And R⁷Independently selected from H, C_1-6Alkyl, -C_1-6alkyl-OH, -C_1-6alkyl-O-C_1-6Alkyl and-C_1-6alkyl-N (C)_1-6Alkyl radical)₂. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-OC (O) NR⁶R⁷And R is⁶And R⁷Independently selected from H, C_1-6Alkyl, -C_1-6alkyl-O-C_1-6Alkyl and-C_1-6alkyl-N (C)_1-6Alkyl radical)₂. Some embodiments are compounds of formula (I), or a medicament thereofA pharmaceutically acceptable salt or solvate thereof, wherein R³is-OC (O) NR⁶R⁷And R is⁶And R⁷Independently selected from C_1-6An alkyl group. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-OC (O) NR⁶R⁷And R is⁶And R⁷Each is-CH₃. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) R⁸. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) R⁸And R is⁸is-C_1-6alkyl-OH. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) R⁸And R is⁸is-C_1-6alkyl-O-C_1-6An alkyl group. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R ³is-N (H) C (O) R⁸And R is⁸Is optionally substituted with one or two independently selected from halogen and C_1-6Phenyl of the radical of alkyl. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) R⁸And R is⁸Is optionally substituted with one or two independently selected from halogen and C_1-6C of the radical of an alkyl group_2-9A heteroaryl group.

Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R³Selected from-N (H) C (O) OR⁵and-OC (O) NR⁶R⁷. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R³Selected from-N (H) C (O) OR⁵and-OC (O) NR⁶R⁷；R⁵Is C_1-6An alkyl group; and R is⁶And R⁷Independently selected from H and C_1-6An alkyl group. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵(ii) a And R is⁵Is methyl. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-OC (O) NR⁶R⁷(ii) a And R is⁶And R⁷Independently selected from H and C_1-6An alkyl group. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-OC (O) NR⁶R⁷(ii) a And R is⁶And R⁷Is C _1-6An alkyl group. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-OC (O) NR⁶R⁷(ii) a And R is⁶And R⁷Is methyl.

Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 0, 1, 2, or 3. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 0. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1, 2, or 3. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 2. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 3. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 4.

Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, -OR⁹、-C(O)OR⁹、-C(O)-C_1-10Alkyl radical, C_1-10Alkyl radical, C_1-10alkyl-OH, C _2-10Alkenyl radical, C_1-10Haloalkyl, C_1-10haloalkyl-OH, C_2-10Haloalkenyl, C_3-12Cycloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl, phenyl and-C_1-6Alkyl-phenyl, wherein phenyl and-C_1-6Alkyl-phenyl optionally substituted with one, two or three independently selected from halogen and C_1-6The radical of an alkyl group. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, -OR⁹、-C(O)OR⁹、C_1-10Alkyl radical, C_1-10alkyl-OH, C_1-10Haloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl and-C_1-6Alkyl-phenyl of which-C_1-6Alkyl-phenyl is optionally substituted with one or two halogens. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁹Independently selected from C_1-10Alkyl radical, C_1-10Haloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl, phenyl and-C_1-6Alkyl-phenyl, wherein phenyl and-C_1-6Alkyl-phenyl optionally substituted with one or two independently selected from halogen and C_1-6The radical of an alkyl group.

Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, whereinSelected from: benzimidazolyl, imidazopyridinyl, purinyl, indolyl, pyrrolopyridinyl, pyrrolopyrimidinyl, benzoxazolyl, benzothiazolyl, imidazopyrazinyl, imidazopyridazinyl, pyrrolopyrazinyl, pyrrolopyridazinyl, oxazolopyridyl, oxazolopyrimidinyl, oxazolopyridazinyl, benzofuranyl, furopyridinyl, furopyrimidinyl, furopyrazinyl, furopyridazinyl, thiazolopyridyl, thiazolopyrimidinyl, thiazolopyridinyl, thiazolopyridazinyl, benzothienyl, thienopyridinyl, thienopyrimidinyl, thienopyrazinyl, thienopyridazinyl, indolizinyl, pyrrolotriazinyl, imidazotriazinyl, triazolopyridinyl, triazolopyridazinyl, triazolopyrimidinyl, and triazolopyrazinyl.

Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, whereinSelected from: some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, whereinSelected from: some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein Is composed ofSome embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R⁴Is C_1-10An alkyl group. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R⁴Is C_1-10A haloalkyl group. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R⁴is-OR⁹. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein R⁴is-OR⁹And R is⁹is-C optionally substituted with one or two halogens_1-6Alkyl-phenyl.

Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, whereinSelected from: some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein Is composed ofSome embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (I), or a pharmaceutically acceptable salt thereofAn acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed of

Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, whereinSelected from:and each R⁴Independently selected from halogen and optionally substituted alkyl. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is ⁴Independently selected from the group consisting of chloro, fluoro, methyl, ethyl, butyl and isobutyl. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from fluorine, methyl and isobutyl.

Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, -OR⁹、-N(R¹⁰)₂、C_1-10Alkyl radical, C_2-10Alkenyl radical, C_1-10Haloalkyl and-C_1-6alkyl-C_3-12A cycloalkyl group. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, -OR⁹、-N(R¹⁰)₂、C_1-10Alkyl and C_1-10A haloalkyl group. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, -OR⁹、-N(R¹⁰)₂、C_1-10Alkyl and C_1-10Haloalkyl, and each R⁹Is C_1-10An alkyl group. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, C_1-10Alkyl and C_1-10A haloalkyl group. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen and C_1-10An alkyl group.

Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein p is 0. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein p is 1. Some embodiments are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein p is 2.

In another embodiment, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof,

wherein:

is a 9-membered bicyclic heteroaryl ring;

x, Y and Z is ═ C (R)¹¹)-；

R¹And R²Independently selected from H and C_1-6An alkyl group, a carboxyl group,

R³selected from-N (H) C (O) OR⁵and-OC (O) NR⁶R⁷；

Each R⁴Independently selected from halogen and C_1-10An alkyl group;

R⁵is C_1-6An alkyl group;

R⁶and R⁷Independently selected from H and C_1-6An alkyl group;

each R¹¹Independently selected from H, halogen and C_1-6An alkyl group;

n is 0, 1, 2, 3 or 4; and

p is 0, 1 or 2.

In another embodiment, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, wherein:

is benzimidazolyl, imidazopyridinyl, purinyl, indolyl, pyrrolopyridinyl, pyrrolopyrimidinyl, benzoxazolyl, benzothiazolyl, imidazopyrazinyl, imidazopyridazinyl, pyrrolopyrazinyl, pyrrolopyridazinyl, oxazolopyridyl, oxazolopyrimidinyl, oxazolopyridazinyl, benzofuranyl, furopyridinyl, furopyrimidinyl, furopyrazinyl, furopyridazinyl, thiazolopyridyl, thiazolopyrimidinyl, thiazopyridyl A thienopyrazinyl group, a thiazolopyridazinyl group, a benzothiophenyl group, a thienopyridyl group, a thienopyrimidinyl group, a thienopyrazinyl group, a thienopyridazinyl group, an indolizinyl group, a pyrrolotriazinyl group, an imidazotriazinyl group, a triazolopyridinyl group, a triazolopyridazinyl group, a triazolopyrimidinyl group or a triazolopyrazinyl group;

x, Y and Z is ═ C (R)¹¹)-；

R¹And R²Independently selected from H and C_1-6An alkyl group;

R³selected from-N (H) C (O) OR⁵and-OC (O) NR⁶R⁷；

Each R⁴Independently selected from halogen and C_1-10An alkyl group;

R⁵is C_1-6An alkyl group;

R⁶and R⁷Independently selected from H and C_1-6An alkyl group;

each R¹¹Independently selected from H, halogen and C_1-6An alkyl group;

n is 0, 1, 2, 3 or 4; and

p is 0, 1 or 2.

In another embodiment, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof,

wherein:

is benzimidazolyl, imidazopyridinyl, purinyl, indolyl, pyrrolopyridinyl, pyrrolopyrimidinyl, benzoxazolyl or benzothiazolyl;

x, Y and Z is ═ C (R)¹¹)-；

R¹And R²Independently selected from H and C_1-6An alkyl group;

R³selected from-N (H) C (O) OR⁵and-OC (O) NR⁶R⁷；

Each R⁴Independently selected from halogen and C_1-10An alkyl group;

R⁵is C_1-6An alkyl group;

R⁶and R⁷Independently selected from H and C_1-6An alkyl group;

each R¹¹Independently selected from H, halogen and C _1-6An alkyl group;

n is 0, 1, 2, 3 or 4; and

p is 0, 1 or 2.

In another embodiment, the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof,

wherein:

is benzimidazolyl, imidazopyridinyl or pyrrolopyrimidyl;

x, Y and Z is ═ C (R)¹¹)-；

R¹And R²Independently selected from H and C_1-6An alkyl group;

R³selected from-N (H) C (O) OR⁵and-OC (O) NR⁶R⁷；

Each R⁴Independently selected from halogen and C_1-10An alkyl group;

R⁵is C_1-6An alkyl group;

R⁶and R⁷Independently selected from H and C_1-6An alkyl group;

each R¹¹Independently selected from H, halogen and C_1-6An alkyl group;

n is 0, 1, 2, 3 or 4; and

p is 0, 1 or 2.

Some embodiments are compounds having the structure of formula (II), or a pharmaceutically acceptable salt or solvate thereof:

wherein:

is a 9-membered bicyclic heteroaryl ring;

x, Y and Z are selected from ═ C (R)¹¹) -and-N-wherein at least two of X, Y and Z are ═ C (R)¹¹)-；

R³selected from-N (H) C (O) OR⁵、-OC(O)NR⁶R⁷、-N(H)C(O)NR⁶R⁷and-N (H) C (O) R⁸；

Each R⁴Independently selected from halogen, -CN, -OR⁹、-SR⁹、-N(R¹⁰)₂、-S(O)R⁹、-S(O)₂R⁹、-NHS(O)₂R⁹、-S(O)₂N(R¹⁰)₂、-C(O)R⁹、-C(O)OR⁹、-OC(O)R⁹、-C(O)N(R¹⁰)₂、-OC(O)N(R¹⁰)₂、-NR¹⁰C(O)N(R¹⁰)₂、-NR¹⁰C(O)R⁹、-NR¹⁰C(O)OR⁹、C_1-10Alkyl radical, C _1-10alkyl-OH, C_1-10alkyl-OR⁹、C_2-10Alkenyl radical, C_2-10Alkynyl, C_1-10Haloalkyl, C_1-10haloalkyl-OH, C_2-10Haloalkenyl, C_3-12Cycloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl, -C_2-6alkenyl-C_3-12Cycloalkyl, phenyl, -C_1-6Alkyl-phenyl, -C_2-6Alkenyl-phenyl, C_2-9Heterocycloalkyl and C_2-9Heteroaryl, in which phenyl, -C_1-6Alkyl-phenyl, -C_2-6Alkenyl-phenyl, C_2-9Heterocycloalkyl and C_2-9Heteroaryl is optionally substituted with one, two or three independently selected from halogen and C_1-6A group of alkyl groups;

R⁸is selected from C_1-6Alkyl radical, C_1-6Haloalkyl, -C _1-6alkyl-OH, -C_1-6alkyl-O-C_1-6Alkyl radical, C_3-6Cycloalkyl, phenyl, C_2-9Heterocycloalkyl and C_2-9Heteroaryl group, wherein C_3-6Cycloalkyl, phenyl, C_2-9Heterocycloalkyl and C_2-9Heteroaryl is optionally substituted with one or two substituents independently selected from halogen and C_1-6A group of alkyl groups;

each R⁹Independently selected from C_1-10Alkyl radical, C_1-10Haloalkyl, C_3-12Cycloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl, phenyl, -C_1-6Alkyl-phenyl and C_2-9Heteroaryl, in which phenyl, -C_1-6Alkyl-phenyl and C_2-9Heteroaryl is optionally substituted with one or two substituents independently selected from halogen and C_1-6A group of alkyl groups;

each R¹⁰Independently selected from H, C_1-10Alkyl, aryl, heteroaryl, and heteroaryl,C_1-10Haloalkyl, C_3-12Cycloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl, phenyl, -C_1-6Alkyl-phenyl and C_2-9Heteroaryl, in which phenyl, -C_1-6Alkyl-phenyl and C_2-9Heteroaryl is optionally substituted with one or two substituents independently selected from halogen and C_1-6A group of alkyl groups;

each R¹¹Independently selected from H, halogen, C_1-6Alkyl and C_1-6A haloalkyl group;

n is 0, 1, 2, 3 or 4; and

p is 0, 1 or 2.

Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein X, Y and Z are each ═ C (R)¹¹) -. In some embodiments of the compound of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein X and Y are each ═ c (h) -; and Z is ═ C (CH) -, (CH) ₃) -or ═ c (cl) -. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein X, Y and Z are each ═ c (h) -. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein X and Y are each ═ c (h) -, and Z is each ═ c (cl) -. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein X and Y are each ═ C (h) -, and Z is each ═ C (CH)₃) -. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein X is ═ N-, and Y is ═ C (R)¹¹) -, and Z is ═ C (R)¹¹) -. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein X is ═ N-, Y is ═ c (h) -, and Z is ═ c (h) -. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein X is ═ C (R)¹¹) -, Y is ═ N-, and Z is ═ C (R)¹¹) -. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein X is ═ c (h) -, Y is ═ N-, and Z is ═ c (h) -. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solution thereof A compound of formula (I) wherein X is ═ C (R)¹¹) -, Y is ═ C (R)¹¹) -, and Z is ═ N-. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein X is ═ c (h) -, Y is ═ c (h) -, and Z is ═ N-.

Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R¹And R²Independently selected from H and C_1-6An alkyl group. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R¹And R²Each is H. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R¹And R²Each is C_1-6An alkyl group. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R¹And R²Each is-CH₃. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R¹And R²Together with the nitrogen to which they are attached form a 3-, 4-, 5-or 6-membered heterocycloalkyl ring, optionally substituted with one or two substituents independently selected from halogen and C_1-6The radical of an alkyl group. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹And R²Together with the nitrogen to which they are attached form an unsubstituted 3-, 4-, 5-, or 6-membered heterocycloalkyl ring. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R¹And R²Together with the nitrogen to which they are attached form an unsubstituted 3-membered heterocycloalkyl ring. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R¹And R²Together with the nitrogen to which they are attached form an unsubstituted 4-membered heterocycloalkyl ring. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R¹And R²Together with the nitrogen to which they are attached form an unsubstituted 5-membered heterocycloalkyl ring. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R¹And R²Together with the nitrogen to which they are attached form an unsubstituted 6-membered heterocycloalkyl ring.

Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵And R is⁵Is selected from C_1-6Alkyl, -C _1-6alkyl-OH, C_1-6alkyl-O-C_1-6Alkyl radical, C_1-6alkyl-O-C (O) C_1-6Alkyl radical, C_2-9Heterocycloalkyl, -C_1-6alkyl-C_2-9Heterocycloalkyl, -C_1-6Alkyl-phenyl and C_2-9A heteroaryl group. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵And R is⁵Is selected from C_1-6Alkyl, -C_1-6alkyl-OH, -C_1-6alkyl-O-C_1-6Alkyl, -C_1-6alkyl-C_2-9Heterocycloalkyl and-C_1-6Alkyl-phenyl. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵And R is⁵Is C_1-6An alkyl group. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵And R is⁵is-CH₃. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵And R is⁵is-C_1-6alkyl-OH. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵And R is⁵is-C_1-6alkyl-O-C_1-6An alkyl group. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵And R is⁵is-C _1-6alkyl-C_2-9A heterocycloalkyl group. Some embodiments are compounds of formula (II)Or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵And R is⁵is-C_1-6Alkyl-phenyl. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵And R is⁵is-CH₂-phenyl. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-OC (O) NR⁶R⁷. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-OC (O) NR⁶R⁷And R is³is-N (H) C (O) NR⁶R⁷. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-OC (O) NR⁶R⁷And R is⁶And R⁷Independently selected from H, C_1-6Alkyl, -C_1-6alkyl-OH, -C_1-6alkyl-O-C_1-6Alkyl and-C_1-6alkyl-N (C)_1-6Alkyl radical)₂. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-OC (O) NR⁶R⁷And R is⁶And R⁷Independently selected from H, C_1-6Alkyl, -C_1-6alkyl-O-C_1-6Alkyl and-C_1-6alkyl-N (C)_1-6Alkyl radical)₂. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ³is-OC (O) NR⁶R⁷And R is⁶And R⁷Independently selected from C_1-6An alkyl group. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-OC (O) NR⁶R⁷And R is⁶And R⁷Each is-CH₃. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) R⁸. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O)R⁸And R is⁸is-C_1-6alkyl-OH. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) R⁸And R is⁸is-C_1-6alkyl-O-C_1-6An alkyl group. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) R⁸And R is⁸Is optionally substituted with one or two independently selected from halogen and C_1-6Phenyl of the radical of alkyl. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) R⁸And R is⁸Is optionally substituted with one or two independently selected from halogen and C_1-6C of the radical of an alkyl group_2-9A heteroaryl group.

Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ³Selected from-N (H) C (O) OR⁵and-OC (O) NR⁶R⁷. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R³Selected from-N (H) C (O) OR⁵and-OC (O) NR⁶R⁷；R⁵Is C_1-6An alkyl group; and R is⁶And R⁷Independently selected from H and C_1-6An alkyl group. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵(ii) a And R is⁵Is methyl. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-OC (O) NR⁶R⁷(ii) a And R is⁶And R⁷Independently selected from H and C_1-6An alkyl group. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-OC (O) NR⁶R⁷(ii) a And R is⁶And R⁷Is C_1-6An alkyl group. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-OC (O) NR⁶R⁷(ii) a And R is⁶And R⁷Is methyl.

Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 0, 1, 2, or 3. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 0. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1, 2, or 3. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 2. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 3. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 4.

Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, -OR⁹、-C(O)OR⁹、-C(O)-C_1-10Alkyl radical, C_1-10Alkyl radical, C_1-10alkyl-OH, C_2-10Alkenyl radical, C_1-10Haloalkyl, C_1-10haloalkyl-OH, C_2-10Haloalkenyl, C_3-12Cycloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl, phenyl and-C_1-6Alkyl-phenyl, wherein phenyl and-C_1-6Alkyl-phenyl optionally substituted with one, two or three independently selected from halogen and C_1-6The radical of an alkyl group. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, -OR⁹、-C(O)OR⁹、C_1-10Alkyl radical, C_1-10alkyl-OH, C_1-10Haloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl and-C_1-6Alkyl-phenyl of which-C_1-6Alkyl-phenyl is optionally substituted with one or two halogens. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁹Independently selected from C_1-10Alkyl radical, C_1-10Haloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl, phenyl and-C_1-6Alkyl-phenyl, wherein phenyl and-C_1-6Alkyl-phenyl optionally substituted with one or two independently selected from halogen and C_1-6The radical of an alkyl group.

Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein Selected from: benzimidazolyl, imidazopyridinyl, purinyl, indolyl, pyrrolopyridinyl, pyrrolopyrimidinyl, benzoxazolyl, benzothiazolyl, imidazopyrazinyl, imidazopyridazinyl, pyrrolopyrazinyl, pyrrolopyridazinyl, oxazolopyridyl, oxazolopyrimidinyl, oxazolopyridazinyl, benzofuranyl, furopyridinyl, furopyrimidinyl, furopyrazinyl, furopyridazinyl, thiazolopyridyl, thiazolopyrimidinyl, thiazolopyridinyl, thiazolopyridazinyl, benzothienyl, thienopyridinyl, thienopyrimidinyl, thienopyrazinyl, thienopyridazinyl, indolizinyl, pyrrolotriazinyl, imidazotriazinyl, triazolopyridinyl, triazolopyridazinyl, triazolopyrimidinyl, and triazolopyrazinyl.

Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein Selected from: some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, whereinSelected from: some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R⁴Is C_1-10An alkyl group. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R ⁴Is C_1-10A haloalkyl group. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R⁴is-OR⁹. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein R⁴is-OR⁹And R is⁹is-C optionally substituted with one or two halogens_1-6Alkyl-phenyl.

Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, whereinSelected from: some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (II), or a pharmaceutically acceptable salt thereofOr a solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein Is composed ofSome embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed of

Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, whereinSelected from:and each R⁴Independently selected from halogen and optionally substituted alkyl. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from the group consisting of chloro, fluoro, methyl, ethyl, butyl and isobutyl. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from fluorine, methyl and isobutyl.

Some embodiments are compounds of formula (II)Or a pharmaceutically acceptable salt or solvate thereof, wherein each R is ⁴Independently selected from halogen, -OR⁹、-N(R¹⁰)₂、C_1-10Alkyl radical, C_2-10Alkenyl radical, C_1-10Haloalkyl and-C_1-6alkyl-C_3-12A cycloalkyl group. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, -OR⁹、-N(R¹⁰)₂、C_1-10Alkyl and C_1-10A haloalkyl group. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, -OR⁹、-N(R¹⁰)₂、C_1-10Alkyl and C_1-10Haloalkyl, and each R⁹Is C_1-10An alkyl group. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, C_1-10Alkyl and C_1-10A haloalkyl group. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen and C_1-10An alkyl group.

Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein p is 0. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein p is 1. Some embodiments are compounds of formula (II), or a pharmaceutically acceptable salt or solvate thereof, wherein p is 2.

In another embodiment, the invention relates to a compound of formula (II), or a pharmaceutically acceptable salt or solvate thereof,

wherein:

is a 9-membered bicyclic heteroaryl ring;

x, Y and Z is ═ C (R)¹¹)-；

R¹And R²Independently selected from H and C_1-6An alkyl group, a carboxyl group,

R³selected from-N (H) C (O) OR⁵and-OC (O) NR⁶R⁷；

Each R⁴Independently selected from halogen and C_1-10An alkyl group;

R⁵is C_1-6An alkyl group;

R⁶and R⁷Independently selected from H and C_1-6An alkyl group;

each R¹¹Independently selected from H, halogen and C_1-6An alkyl group;

n is 0, 1, 2, 3 or 4; and

p is 0, 1 or 2.

In another embodiment, the invention relates to a compound of formula (II), or a pharmaceutically acceptable salt or solvate thereof,

wherein:

X, Y and Z is ═ C (R)¹¹)-；

R¹And R²Independently selected from H and C_1-6An alkyl group, a carboxyl group,

R³selected from-N (H) C (O) OR⁵and-OC (O)NR⁶R⁷；

Each R⁴Independently selected from halogen and C_1-10An alkyl group;

R⁵is C_1-6An alkyl group;

R⁶and R⁷Independently selected from H and C_1-6An alkyl group;

each R¹¹Independently selected from H, halogen and C_1-6An alkyl group;

n is 0, 1, 2, 3 or 4; and

p is 0, 1 or 2.

In another embodiment, the invention relates to a compound of formula (II), or a pharmaceutically acceptable salt or solvate thereof,

wherein:

is benzimidazolyl, imidazopyridinyl, purinyl, indolyl, pyrrolopyridinyl, pyrrolopyrimidinyl, benzoxazolyl or benzothiazolyl;

x, Y and Z is ═ C (R)¹¹)-；

R¹And R²Independently selected from H and C_1-6An alkyl group, a carboxyl group,

R³selected from-N (H) C (O) OR⁵and-OC (O) NR⁶R⁷；

Each R⁴Independently selected from halogen and C_1-10An alkyl group;

R⁵is C_1-6An alkyl group;

R⁶and R⁷Independently selected from H and C_1-6An alkyl group;

each R¹¹Independently selected from H, halogen and C_1-6An alkyl group;

n is 1, 2 or 3; and

p is 1.

In another embodiment, the invention relates to a compound of formula (II), or a pharmaceutically acceptable salt or solvate thereof,

wherein:

is benzimidazolyl, imidazopyridinyl or pyrrolopyridinyl;

x, Y and Z is ═ C (R)¹¹)-；

R¹And R²Independently selected from H and C_1-6An alkyl group, a carboxyl group,

R³Selected from-N (H) C (O) OR⁵and-OC (O) NR⁶R⁷；

Each R⁴Independently selected from halogen and C_1-10An alkyl group;

R⁵is C_1-6An alkyl group;

R⁶and R⁷Independently selected from H and C_1-6An alkyl group;

each R¹¹Independently selected from H, halogen and C_1-6An alkyl group;

n is 1, 2 or 3; and

p is 1.

Another aspect is a compound having the structure of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof:

wherein:

is a 9-membered bicyclic heteroaryl ring;

R¹and R²Independently selected from H, C_1-6Alkyl and-C_1-6alkyl-OH; or R¹And R²Together with the nitrogen to which they are attached form a 3-, 4-, 5-or 6-membered heterocycloalkyl ring, optionally substituted with one or two substituents independently selected from halogen and C_1-6A group of alkyl groups;

R³selected from-N (H) C (O) OR⁵、-OC(O)NR⁶R⁷、-N(H)C(O)NR⁶R⁷and-N (H) C (O) R⁸；

each R⁹Independently selected from C_1-10Alkyl radical, C_1-10Haloalkyl, C_3-12Cycloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl, phenyl, -C_1-6Alkyl-phenyl and C_2-9Heteroaryl, in which phenyl, -C_1-6Alkyl-phenyl and C _2-9Heteroaryl is optionally substituted with one or two substituents independently selected from halogen and C_1-6A group of alkyl groups;

n is 0, 1, 2, 3 or 4.

Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is¹And R²Independently selected from H and C_1-6An alkyl group. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is¹And R²Each is H. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is¹And R²Each is C_1-6An alkyl group. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is¹And R²Each is-CH₃. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is¹And R²Together with the nitrogen to which they are attached form a 3-, 4-, 5-or 6-membered heterocycloalkyl ring, optionally substituted with one or two substituents independently selected from halogen and C _1-6The radical of an alkyl group. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is¹And R²Together with the nitrogen to which they are attached form an unsubstituted 3-, 4-, 5-, or 6-membered heterocycloalkyl ring. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is¹And R²Together with the nitrogen to which they are attached form an unsubstituted 3-membered heterocycloalkyl ring. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is¹And R²Together with the nitrogen to which they are attached form an unsubstituted 4-membered heterocycloalkyl ring. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is¹And R²Together with the nitrogen to which they are attached form an unsubstituted 5-membered heterocycloalkyl ring. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is¹And R²Together with the nitrogen to which they are attached form an unsubstituted 6-membered heterocycloalkyl ring.

Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) OR⁵. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is ³is-N (H) C (O) OR⁵And R is⁵Is selected from C_1-6Alkyl, -C_1-6alkyl-OH, C_1-6alkyl-O-C_1-6Alkyl radical, C_1-6alkyl-O-C (O) C_1-6Alkyl radical, C_2-9Heterocycloalkyl, -C_1-6alkyl-C_2-9Heterocycloalkyl, -C_1-6Alkyl-phenyl and C_2-9A heteroaryl group. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) OR⁵And R is⁵Is selected from C_1-6Alkyl, -C_1-6alkyl-OH, -C_1-6alkyl-O-C_1-6Alkyl, -C_1-6alkyl-C_2-9Heterocycloalkyl and-C_1-6Alkyl-phenyl. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) OR⁵And R is⁵Is C_1-6An alkyl group. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) OR⁵And R is⁵is-CH₃. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) OR⁵And R is⁵is-C_1-6alkyl-OH. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) OR⁵And R is⁵is-C_1-6alkyl-O-C_1-6An alkyl group. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is ³is-N (H) C (O) OR⁵And R is⁵is-C_1-6alkyl-C_2-9A heterocycloalkyl group. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) OR⁵And R is⁵is-C_1-6Alkyl-phenyl. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) OR⁵And R is⁵is-CH₂-phenyl. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-OC (O) NR⁶R⁷. Some embodiments are compounds of formula (IIa), or a medicament thereofA pharmaceutically acceptable salt or solvate thereof, wherein R³is-OC (O) NR⁶R⁷And R is³is-N (H) C (O) NR⁶R⁷. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-OC (O) NR⁶R⁷And R is⁶And R⁷Independently selected from H, C_1-6Alkyl, -C_1-6alkyl-OH, -C_1-6alkyl-O-C_1-6Alkyl and-C_1-6alkyl-N (C)_1-6Alkyl radical)₂. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-OC (O) NR⁶R⁷And R is⁶And R⁷Independently selected from H, C_1-6Alkyl, -C_1-6alkyl-O-C_1-6Alkyl and-C_1-6alkyl-N (C)_1-6Alkyl radical)₂. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is ³is-OC (O) NR⁶R⁷And R is⁶And R⁷Independently selected from C_1-6An alkyl group. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-OC (O) NR⁶R⁷And R is⁶And R⁷Each is-CH₃. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) R⁸. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) R⁸And R is⁸is-C_1-6alkyl-OH. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) R⁸And R is⁸is-C_1-6alkyl-O-C_1-6An alkyl group. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) R⁸And R is⁸Is optionally substituted with one or two independently selected from halogen and C_1-6Phenyl of the radical of alkyl. ASome embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) R⁸And R is⁸Is optionally substituted with one or two independently selected from halogen and C_1-6C of the radical of an alkyl group_2-9A heteroaryl group.

Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 0, 1, 2, or 3. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 0. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1, 2, or 3. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 2. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 3. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 4.

Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, -OR⁹、-C(O)OR⁹、-C(O)-C_1-10Alkyl radical, C_1-10Alkyl radical, C_1-10alkyl-OH, C_2-10Alkenyl radical, C_1-10Haloalkyl, C_1-10haloalkyl-OH, C_2-10Haloalkenyl, C_3-12Cycloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl, phenyl and-C_1-6Alkyl-phenyl, wherein phenyl and-C_1-6Alkyl-phenyl optionally substituted with one, two or three independently selected from halogen and C_1-6The radical of an alkyl group. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, -OR⁹、-C(O)OR⁹、C_1-10Alkyl radical, C_1-10alkyl-OH, C_1-10Haloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl and-C_1-6Alkyl-phenyl of which-C_1-6Alkyl-phenyl is optionally substituted with one or two halogens. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁹Independently selected from C_1-10Alkyl radical, C_1-10Haloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl, phenyl and-C_1-6Alkyl-phenyl, wherein phenyl and-C_1-6Alkyl-phenyl optionally substituted with one or two independently selected from halogen and C_1-6The radical of an alkyl group.

Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein Selected from: some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, whereinSelected from: some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome areAn embodiment is a compound of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is⁴Is C_1-10An alkyl group. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is ⁴Is C_1-10A haloalkyl group. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is⁴is-OR⁹. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein R is⁴is-OR⁹And R is⁹is-C optionally substituted with one or two halogens_1-6Alkyl-phenyl.

Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, whereinSelected from: some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein Is composed ofSome embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed of

Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, -OR⁹、-N(R¹⁰)₂、C_1-10Alkyl radical, C_2-10Alkenyl radical, C_1-10Haloalkyl and-C_1-6alkyl-C_3-12A cycloalkyl group. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, -OR⁹、-N(R¹⁰)₂、C_1-10Alkyl and C_1-10A haloalkyl group. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, -OR⁹、-N(R¹⁰)₂、C_1-10Alkyl and C_1-10Haloalkyl, and each R⁹Is C _1-10An alkyl group. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, C_1-10Alkyl and C_1-10A haloalkyl group. Some embodiments are compounds of formula (IIa), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen and C_1-10An alkyl group.

Another aspect is a compound having the structure of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof:

wherein:

is a 9-membered bicyclic heteroaryl ring;

R¹and R²Independently selected from H, C_1-6Alkyl and-C_1-6alkyl-OH; or R¹And R²With itThe nitrogen to which they are attached together form a 3-, 4-, 5-or 6-membered heterocycloalkyl ring, optionally substituted with one or two substituents independently selected from halogen and C_1-6A group of alkyl groups;

R³selected from-N (H) C (O) OR⁵、-OC(O)NR⁶R⁷、-N(H)C(O)NR⁶R⁷and-N (H) C (O) R⁸；

Each R⁴Independently selected from halogen, -CN, -OR⁹、-SR⁹、-N(R¹⁰)₂、-S(O)R⁹、-S(O)₂R⁹、-NHS(O)₂R⁹、-S(O)₂N(R¹⁰)₂、-C(O)R⁹、-C(O)OR⁹、-OC(O)R⁹、-C(O)N(R¹⁰)₂、-OC(O)N(R¹⁰)₂、-NR¹⁰C(O)N(R¹⁰)₂、-NR¹⁰C(O)R⁹、-NR¹⁰C(O)OR⁹、C_1-10Alkyl radical, C_1-10alkyl-OH, C_1-10alkyl-OR⁹、C_2-10Alkenyl radical, C_2-10Alkynyl, C_1-10Haloalkyl, C_1-10haloalkyl-OH, C_2-10Haloalkenyl, C_3-12Cycloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl, -C_2-6alkenyl-C_3-12Cycloalkyl, phenyl, -C_1-6Alkyl-phenyl, -C_2-6Alkenyl-phenyl, C_2-9Heterocycloalkyl and C_2-9Heteroaryl, in which phenyl, -C_1-6Alkyl-phenyl, -C_2-6Alkenyl-phenyl, C _2-9Heterocycloalkyl and C_2-9Heteroaryl is optionally substituted with one, two or three independently selected from halogen and C_1-6A group of alkyl groups;

each R⁹Independently selected from C_1-10Alkyl radical, C_1-10Haloalkyl, C_3-12Cycloalkyl, -C_1-6alkyl-C _3-12Cycloalkyl, phenyl, -C_1-6Alkyl-phenyl and C_2-9Heteroaryl, in which phenyl, -C_1-6Alkyl-phenyl and C_2-9Heteroaryl is optionally substituted with one or two substituents independently selected from halogen and C_1-6A group of alkyl groups;

n is 0, 1, 2, 3 or 4.

Some areAn embodiment is a compound of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R is¹And R²Independently selected from H and C_1-6An alkyl group. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R¹And R²Each is H. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R¹And R²Each is C_1-6An alkyl group. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R¹And R²Each is-CH₃. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ¹And R²Together with the nitrogen to which they are attached form a 3-, 4-, 5-or 6-membered heterocycloalkyl ring, optionally substituted with one or two substituents independently selected from halogen and C_1-6The radical of an alkyl group. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R¹And R²Together with the nitrogen to which they are attached form an unsubstituted 3-, 4-, 5-, or 6-membered heterocycloalkyl ring. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R¹And R²Together with the nitrogen to which they are attached form an unsubstituted 3-membered heterocycloalkyl ring. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R¹And R²Together with the nitrogen to which they are attached form an unsubstituted 4-membered heterocycloalkyl ring. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R¹And R²Together with the nitrogen to which they are attached form an unsubstituted 5-membered heterocycloalkyl ring. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R¹And R²Together with the nitrogen to which they are attached form an unsubstituted 6-membered heterocycloalkyl ring.

Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵And R is⁵Is selected from C_1-6Alkyl, -C_1-6alkyl-OH, C_1-6alkyl-O-C_1-6Alkyl radical, C_1-6alkyl-O-C (O) C_1-6Alkyl radical, C_2-9Heterocycloalkyl, -C_1-6alkyl-C_2-9Heterocycloalkyl, -C_1-6Alkyl-phenyl and C_2-9A heteroaryl group. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵And R is⁵Is selected from C_1-6Alkyl, -C_1-6alkyl-OH, -C_1-6alkyl-O-C_1-6Alkyl, -C_1-6alkyl-C_2-9Heterocycloalkyl and-C_1-6Alkyl-phenyl. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵And R is⁵Is C_1-6An alkyl group. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵And R is⁵is-CH₃. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵And R is⁵is-C_1-6alkyl-OH. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ³is-N (H) C (O) OR⁵And R is⁵is-C_1-6alkyl-O-C_1-6An alkyl group. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵And R is⁵is-C_1-6alkyl-C_2-9A heterocycloalkyl group. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵And R is⁵is-C_1-6Alkyl-phenyl. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵And R is⁵is-CH₂-phenyl. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-OC (O) NR⁶R⁷. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-OC (O) NR⁶R⁷And R is³is-N (H) C (O) NR⁶R⁷. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-OC (O) NR⁶R⁷And R is⁶And R⁷Independently selected from H, C_1-6Alkyl, -C_1-6alkyl-OH, -C_1-6alkyl-O-C_1-6Alkyl and-C_1-6alkyl-N (C)_1-6Alkyl radical)₂. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ³is-OC (O) NR⁶R⁷And R is⁶And R⁷Independently selected from H, C_1-6Alkyl, -C_1-6alkyl-O-C_1-6Alkyl and-C_1-6alkyl-N (C)_1-6Alkyl radical)₂. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-OC (O) NR⁶R⁷And R is⁶And R⁷Independently selected from C_1-6An alkyl group. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-OC (O) NR⁶R⁷And R is⁶And R⁷Each is-CH₃. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) R⁸. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) R⁸And R is⁸is-C_1-6alkyl-OH. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) R⁸And R is⁸is-C_1-6Alkyl radical-O-C_1-6An alkyl group. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) R⁸And R is⁸Is optionally substituted with one or two independently selected from halogen and C_1-6Phenyl of the radical of alkyl. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ³is-N (H) C (O) R⁸And R is⁸Is optionally substituted with one or two independently selected from halogen and C_1-6C of the radical of an alkyl group_2-9A heteroaryl group.

Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 0, 1, 2, or 3. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 0. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1, 2, or 3. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 2. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 3. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 4.

Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, -OR⁹、-C(O)OR⁹、-C(O)-C_1-10Alkyl radical, C_1-10Alkyl radical, C_1-10alkyl-OH, C_2-10Alkenyl radical, C _1-10Haloalkyl, C_1-10haloalkyl-OH, C_2-10Haloalkenyl, C_3-12Cycloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl, phenyl and-C_1-6Alkyl-phenyl, wherein phenyl and-C_1-6Alkyl-phenyl optionally substituted with one, two or three independently selected from halogen and C_1-6The radical of an alkyl group. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt thereofA pharmaceutically acceptable salt or solvate, wherein each R⁴Independently selected from halogen, -OR⁹、-C(O)OR⁹、C_1-10Alkyl radical, C_1-10alkyl-OH, C_1-10Haloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl and-C_1-6Alkyl-phenyl of which-C_1-6Alkyl-phenyl is optionally substituted with one or two halogens. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁹Independently selected from C_1-10Alkyl radical, C_1-10Haloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl, phenyl and-C_1-6Alkyl-phenyl, wherein phenyl and-C_1-6Alkyl-phenyl optionally substituted with one or two independently selected from halogen and C_1-6The radical of an alkyl group.

Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, whereinSelected from: some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, whereinSelected from: some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, which InIs composed ofSome embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R⁴Is C_1-10An alkyl group. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R⁴Is C_1-10A haloalkyl group. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R ⁴is-OR⁹. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein R⁴is-OR⁹And R is⁹is-C optionally substituted with one or two halogens_1-6Alkyl-phenyl.

Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, whereinSelected from: some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein Is composed ofSome embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIb), orA pharmaceutically acceptable salt or solvate thereof, whereinIs composed of

Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, -OR⁹、-N(R¹⁰)₂、C_1-10Alkyl radical, C_2-10Alkenyl radical, C_1-10Haloalkyl and-C_1-6alkyl-C_3-12A cycloalkyl group. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, -OR⁹、-N(R¹⁰)₂、C_1-10Alkyl and C_1-10A haloalkyl group. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, -OR⁹、-N(R¹⁰)₂、C_1-10Alkyl and C_1-10Haloalkyl, and each R⁹Is C_1-10An alkyl group. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is ⁴Independently selected from halogen, C_1-10Alkyl and C_1-10A haloalkyl group. Some embodiments are compounds of formula (IIb), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen and C_1-10An alkyl group.

Another aspect is a compound having the structure of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof:

wherein:

is a 9-membered bicyclic heteroaryl ring;

R³selected from-N (H) C (O) OR⁵、-OC(O)NR⁶R⁷、-N(H)C(O)NR⁶R⁷and-N (H) C (O) R⁸；

R⁵Is selected from C_1-6Alkyl, -C_1-6alkyl-OH, -C_1-6alkyl-O-C_1-6Alkyl, -C_1-6alkyl-O-C (O) C_1-6Alkyl radical, C_2-9Heterocycloalkyl, -C_1-6alkyl-C_2-9Heterocycloalkyl, phenyl, -C_1-6Alkyl-phenyl and C_2-9Heteroaryl group, wherein C_2-9Heterocycloalkyl, -C_1-6alkyl-C_2-9Heterocycloalkyl, phenyl, -C_1-6Alkyl-phenyl and C_2-9Heteroaryl is optionally substituted with one or two substituents independently selected from halogen and C_1-6A group of alkyl groups;

each R⁹Independently selected from C_1-10Alkyl radical, C_1-10Haloalkyl, C_3-12Cycloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl, phenyl, -C_1-6Alkyl-phenyl and C_2-9Heteroaryl, in which phenyl, -C_1-6Alkyl-phenyl and C_2-9Heteroaryl is optionally substituted with one or two substituents independently selected from halogen and C _1-6A group of alkyl groups;

n is 0, 1, 2, 3 or 4.

Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is¹And R²Independently selected from H and C_1-6An alkyl group. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is¹And R²Each is H. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is¹And R²Each is C_1-6An alkyl group. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is¹And R²Each is-CH₃. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is¹And R²Together with the nitrogen to which they are attached form a 3-, 4-, 5-or 6-membered heterocycloalkyl ring, optionally substituted with one or two substituents independently selected from halogen and C_1-6The radical of an alkyl group. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is ¹And R²Together with the nitrogen to which they are attached form an unsubstituted 3-, 4-, 5-, or 6-membered heterocycloalkyl ring. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is¹And R²Together with the nitrogen to which they are attached form an unsubstituted 3-membered heterocycloalkyl ring. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is¹And R²Together with the nitrogen to which they are attached form an unsubstituted 4-membered heterocycloalkyl ring. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is¹And R²Together with the nitrogen to which they are attached form an unsubstituted 5-membered heterocycloalkyl ring. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvent thereofCompound (II) wherein R¹And R²Together with the nitrogen to which they are attached form an unsubstituted 6-membered heterocycloalkyl ring.

Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) OR⁵. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) OR⁵And R is⁵Is selected from C _1-6Alkyl, -C_1-6alkyl-OH, C_1-6alkyl-O-C_1-6Alkyl radical, C_1-6alkyl-O-C (O) C_1-6Alkyl radical, C_2-9Heterocycloalkyl, -C_1-6alkyl-C_2-9Heterocycloalkyl, -C_1-6Alkyl-phenyl and C_2-9A heteroaryl group. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) OR⁵And R is⁵Is selected from C_1-6Alkyl, -C_1-6alkyl-OH, -C_1-6alkyl-O-C_1-6Alkyl, -C_1-6alkyl-C_2-9Heterocycloalkyl and-C_1-6Alkyl-phenyl. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) OR⁵And R is⁵Is C_1-6An alkyl group. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) OR⁵And R is⁵is-CH₃. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) OR⁵And R is⁵is-C_1-6alkyl-OH. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) OR⁵And R is⁵is-C_1-6alkyl-O-C_1-6An alkyl group. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) OR ⁵And R is⁵is-C_1-6alkyl-C_2-9A heterocycloalkyl group. Some implementationsThe formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R³is-N (H) C (O) OR⁵And R is⁵is-C_1-6Alkyl-phenyl. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) OR⁵And R is⁵is-CH₂-phenyl. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-OC (O) NR⁶R⁷. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-OC (O) NR⁶R⁷And R is³is-N (H) C (O) NR⁶R⁷. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-OC (O) NR⁶R⁷And R is⁶And R⁷Independently selected from H, C_1-6Alkyl, -C_1-6alkyl-OH, -C_1-6alkyl-O-C_1-6Alkyl and-C_1-6alkyl-N (C)_1-6Alkyl radical)₂. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-OC (O) NR⁶R⁷And R is⁶And R⁷Independently selected from H, C_1-6Alkyl, -C_1-6alkyl-O-C_1-6Alkyl and-C_1-6alkyl-N (C)_1-6Alkyl radical)₂. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is ³is-OC (O) NR⁶R⁷And R is⁶And R⁷Independently selected from C_1-6An alkyl group. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-OC (O) NR⁶R⁷And R is⁶And R⁷Each is-CH₃. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) R⁸. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereofWherein R is³is-N (H) C (O) R⁸And R is⁸is-C_1-6alkyl-OH. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) R⁸And R is⁸is-C_1-6alkyl-O-C_1-6An alkyl group. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) R⁸And R is⁸Is optionally substituted with one or two independently selected from halogen and C_1-6Phenyl of the radical of alkyl. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) R⁸And R is⁸Is optionally substituted with one or two independently selected from halogen and C_1-6C of the radical of an alkyl group_2-9A heteroaryl group.

Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 0, 1, 2, or 3. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 0. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1, 2, or 3. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 2. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 3. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 4.

Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, -OR⁹、-C(O)OR⁹、-C(O)-C_1-10Alkyl radical, C_1-10Alkyl radical, C_1-10alkyl-OH, C_2-10Alkenyl radical, C_1-10Haloalkyl, C_1-10haloalkyl-OH, C_2-10Haloalkenyl, C_3-12Cycloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl, phenyl and-C_1-6Alkyl-phenyl, wherein phenyl and-C_1-6Alkyl-phenyl optionally substituted with one, two or three independently selected from halogen and C_1-6The radical of an alkyl group. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, -OR⁹、-C(O)OR⁹、C_1-10Alkyl radical, C_1-10alkyl-OH, C_1-10Haloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl and-C_1-6Alkyl-phenyl of which-C_1-6Alkyl-phenyl is optionally substituted with one or two halogens. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁹Independently selected from C_1-10Alkyl radical, C_1-10Haloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl, phenyl and-C_1-6Alkyl-phenyl, wherein phenyl and-C_1-6Alkyl-phenyl optionally substituted with one or two independently selected from halogen and C_1-6The radical of an alkyl group.

Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein Selected from: some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, whereinSelected from: some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIc)Or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is⁴Is C_1-10An alkyl group. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is ⁴Is C_1-10A haloalkyl group. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is⁴is-OR⁹. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein R is⁴is-OR⁹And R is⁹is-C optionally substituted with one or two halogens_1-6Alkyl-phenyl.

Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, whereinSelected from: some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein Is composed ofSome embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed of

Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, -OR⁹、-N(R¹⁰)₂、C_1-10Alkyl radical, C_2-10Alkenyl radical, C_1-10Haloalkyl and-C_1-6alkyl-C_3-12A cycloalkyl group. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, -OR⁹、-N(R¹⁰)₂、C_1-10Alkyl and C_1-10A haloalkyl group. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, -OR⁹、-N(R¹⁰)₂、C_1-10Alkyl and C_1-10Haloalkyl, and each R⁹Is C _1-10An alkyl group. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, C_1-10Alkyl and C_1-10A haloalkyl group. Some embodiments are compounds of formula (IIc), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen and C_1-10An alkyl group.

Another aspect is a compound having the structure of formula (IId), or a pharmaceutically acceptable salt or solvate thereof:

wherein:

is a 9-membered bicyclic heteroaryl ring;

R³selected from-N (H) C (O) OR⁵、-OC(O)NR⁶R⁷、-N(H)C(O)NR⁶R⁷and-N (H) C (O) R⁸；

Each R⁴Independently selected from halogen, -CN, -OR⁹、-SR⁹、-N(R¹⁰)₂、-S(O)R⁹、-S(O)₂R⁹、-NHS(O)₂R⁹、-S(O)₂N(R¹⁰)₂、-C(O)R⁹、-C(O)OR⁹、-OC(O)R⁹、-C(O)N(R¹⁰)₂、-OC(O)N(R¹⁰)₂、-NR¹⁰C(O)N(R¹⁰)₂、-NR¹⁰C(O)R⁹、-NR¹⁰C(O)OR⁹、C_1-10Alkyl radical, C_1-10alkyl-OH, C_1-10alkyl-OR⁹、C_2-10Alkenyl radical, C_2-10Alkynyl, C_1-10Haloalkyl, C_1-10haloalkyl-OH, C_2-10Haloalkenyl, C_3-12Cycloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl, -C_2-6alkenyl-C_3-12Cycloalkyl, phenyl, -C_1-6Alkyl-phenyl, -C_2-6Alkenyl-phenyl, C_2-9Heterocycloalkyl and C_2-9Heteroaryl, in which phenyl, -C_1-6Alkyl-phenyl, -C_2-6Alkenyl-phenyl, C _2-9Heterocycloalkyl and C_2-9Heteroaryl is optionally substituted with one, two or three independently selected from halogen and C_1-6A group of alkyl groups;

each R⁹Independently selected from C_1-10Alkyl radical, C_1-10Haloalkyl, C_3-12Cycloalkyl, -C_1-6alkyl-C _3-12Cycloalkyl, phenyl, -C_1-6Alkyl-phenyl and C_2-9Heteroaryl, in which phenyl, -C_1-6Alkyl-phenyl and C_2-9Heteroaryl is optionally substituted with one or two substituents independently selected from halogen and C_1-6A group of alkyl groups;

n is 0, 1, 2, 3 or 4.

Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is¹And R²Independently selected from H and C_1-6An alkyl group. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is¹And R²Each is H. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is¹And R²Each is C_1-6An alkyl group. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is¹And R²Each is-CH₃. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is ¹And R²Together with the nitrogen to which they are attached form a 3-, 4-, 5-or 6-membered heterocycloalkyl ring, optionally substituted with one or two substituents independently selected from halogen and C_1-6The radical of an alkyl group. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is¹And R²Together with the nitrogen to which they are attached form an unsubstituted 3-, 4-, 5-, or 6-membered heterocycloalkyl ring. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is¹And R²Together with the nitrogen to which they are attached form an unsubstituted 3-membered heterocycloalkyl ring. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is¹And R²Together with the nitrogen to which they are attached form an unsubstituted 4-membered ringA heterocycloalkyl ring. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is¹And R²Together with the nitrogen to which they are attached form an unsubstituted 5-membered heterocycloalkyl ring. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is¹And R²Together with the nitrogen to which they are attached form an unsubstituted 6-membered heterocycloalkyl ring.

Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) OR⁵. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) OR⁵And R is⁵Is selected from C_1-6Alkyl, -C_1-6alkyl-OH, C_1-6alkyl-O-C_1-6Alkyl radical, C_1-6alkyl-O-C (O) C_1-6Alkyl radical, C_2-9Heterocycloalkyl, -C_1-6alkyl-C_2-9Heterocycloalkyl, -C_1-6Alkyl-phenyl and C_2-9A heteroaryl group. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) OR⁵And R is⁵Is selected from C_1-6Alkyl, -C_1-6alkyl-OH, -C_1-6alkyl-O-C_1-6Alkyl, -C_1-6alkyl-C_2-9Heterocycloalkyl and-C_1-6Alkyl-phenyl. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) OR⁵And R is⁵Is C_1-6An alkyl group. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) OR⁵And R is⁵is-CH₃. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) OR⁵And R is⁵is-C_1-6alkyl-OH. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is ³is-N (H) C (O) OR⁵And R is⁵is-C_1-6alkyl-O-C_1-6An alkyl group. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) OR⁵And R is⁵is-C_1-6alkyl-C_2-9A heterocycloalkyl group. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) OR⁵And R is⁵is-C_1-6Alkyl-phenyl. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) OR⁵And R is⁵is-CH₂-phenyl. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-OC (O) NR⁶R⁷. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-OC (O) NR⁶R⁷And R is³is-N (H) C (O) NR⁶R⁷. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-OC (O) NR⁶R⁷And R is⁶And R⁷Independently selected from H, C_1-6Alkyl, -C_1-6alkyl-OH, -C_1-6alkyl-O-C_1-6Alkyl and-C_1-6alkyl-N (C)_1-6Alkyl radical)₂. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is ³is-OC (O) NR⁶R⁷And R is⁶And R⁷Independently selected from H, C_1-6Alkyl, -C_1-6alkyl-O-C_1-6Alkyl and-C_1-6alkyl-N (C)_1-6Alkyl radical)₂. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-OC (O) NR⁶R⁷And R is⁶And R⁷Independently selected from C_1-6An alkyl group. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-OC (O) NR⁶R⁷And R is⁶And R⁷Each is-CH₃. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) R⁸. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) R⁸And R is⁸is-C_1-6alkyl-OH. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) R⁸And R is⁸is-C_1-6alkyl-O-C_1-6An alkyl group. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) R⁸And R is⁸Is optionally substituted with one or two independently selected from halogen and C_1-6Phenyl of the radical of alkyl. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is ³is-N (H) C (O) R⁸And R is⁸Is optionally substituted with one or two independently selected from halogen and C_1-6C of the radical of an alkyl group_2-9A heteroaryl group.

Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 0, 1, 2, or 3. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 0. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1, 2, or 3. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 1. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 2. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 3. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein n is 4.

Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, -OR⁹、-C(O)OR⁹、-C(O)-C_1-10Alkyl radical, C_1-10Alkyl radical, C_1-10alkyl-OH, C_2-10Alkenyl radical, C _1-10Haloalkyl, C_1-10haloalkyl-OH, C_2-10Haloalkenyl, C_3-12Cycloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl, phenyl and-C_1-6Alkyl-phenyl, wherein phenyl and-C_1-6Alkyl-phenyl optionally substituted with one, two or three independently selected from halogen and C_1-6The radical of an alkyl group. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, -OR⁹、-C(O)OR⁹、C_1-10Alkyl radical, C_1-10alkyl-OH, C_1-10Haloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl and-C_1-6Alkyl-phenyl of which-C_1-6Alkyl-phenyl is optionally substituted with one or two halogens. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁹Independently selected from C_1-10Alkyl radical, C_1-10Haloalkyl, -C_1-6alkyl-C_3-12Cycloalkyl, phenyl and-C_1-6Alkyl-phenyl, wherein phenyl and-C_1-6Alkyl-phenyl optionally substituted with one or two independently selected from halogen and C_1-6The radical of an alkyl group.

Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, whereinSelected from: some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, whereinSelected from: some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein Is composed ofSome embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is⁴Is C_1-10An alkyl group. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is⁴Is C_1-10A haloalkyl group. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is ⁴is-OR⁹. Some embodiments are compounds of formula (IId), or a pharmaceutically acceptable salt or solvate thereof, wherein R is⁴is-OR⁹And R is⁹is-C optionally substituted with one or two halogens_1-6Alkyl-phenyl.

Another aspect is a compound having the structure of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof:

wherein:

is composed of

R¹And R²Independently selected from C_1-6An alkyl group;

R³selected from-N (H) C (O) OR⁵and-OC (O) NR⁶R⁷；

Each R⁴Independently selected from halogen, -OR⁹、-N(R¹⁰)₂、C_1-10Alkyl radical, C_2-10Alkenyl radical, C_2-10Alkynyl, C_1-10Haloalkyl, C_3-12Cycloalkyl and-C_1-6alkyl-C_3-12A cycloalkyl group;

R⁵is C_1-6An alkyl group;

R⁶and R⁷Independently selected from C_1-6An alkyl group;

each R⁹Independently selected from C_1-10Alkyl radical, C_1-10Haloalkyl and-C_1-6Alkyl-phenyl;

each R¹⁰Independently selected from H and C_1-10An alkyl group; and

R¹¹selected from: H. halogen, C_1-6Alkyl and C_1-6A haloalkyl group.

Some embodiments are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein R is¹And R²Each is-CH₃。

Some embodiments are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) OR⁵. Some embodiments are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-N (H) C (O) OR ⁵And R is⁵is-CH₃. Some embodiments are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-OC (O) NR⁶R⁷. Some embodiments are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein R is³is-OC (O) NR⁶R⁷And R is⁶And R⁷Each is-CH₃。

Some embodiments are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein Is composed ofSome embodiments are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, whereinIs composed ofSome embodiments are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof,whereinIs composed of

Some embodiments are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, -OR⁹、-N(R¹⁰)₂、C_1-10Alkyl radical, C_2-10Alkenyl radical, C_1-10Haloalkyl and-C_1-6alkyl-C_3-12A cycloalkyl group. Some embodiments are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, -OR⁹、-N(R¹⁰)₂、C_1-10Alkyl and C_1-10A haloalkyl group. Some embodiments are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, -OR⁹、-N(R¹⁰)₂、C_1-10Alkyl and C_1-10Haloalkyl, and each R⁹Is C_1-10An alkyl group. Some embodiments are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen, C_1-10Alkyl and C_1-10A haloalkyl group. Some embodiments are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein each R is⁴Independently selected from halogen and C_1-10An alkyl group.

Described herein are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein:

is composed of

R¹And R²Independently of each otherIs selected from C_1-6An alkyl group;

R³selected from-N (H) C (O) OR⁵and-OC (O) NR⁶R⁷；

R⁴Is C_1-10An alkyl group;

R⁵is C_1-6An alkyl group;

R⁶and R⁷Independently selected from C_1-6An alkyl group; and

R¹¹selected from: H. halogen and C_1-6An alkyl group.

Described herein are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein:

is composed of

R¹And R²Independently selected from C_1-6An alkyl group;

R³is-N (H) C (O) OR⁵；

R⁴Is C_1-10An alkyl group;

R⁵is C_1-6An alkyl group; and

R¹¹is H.

Described herein are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein:

is composed of

R¹And R²Independently selected from C_1-6An alkyl group;

R³is-N (H) C (O) OR⁵；

R⁴Is C_1-10An alkyl group;

R⁵is C_1-6An alkyl group; and

R¹¹is halogen.

Described herein are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein:

is composed of

R¹And R²Independently selected from C_1-6An alkyl group;

R³is-N (H) C (O) OR⁵；

R⁴Is C_1-10An alkyl group;

R⁵is C_1-6An alkyl group; and

R¹¹is C_1-6An alkyl group.

Described herein are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein:

is composed of

R¹And R²Independently selected from C_1-6An alkyl group;

R³is-OC (O) NR⁶R⁷；

R⁴Is C_1-10An alkyl group;

R⁶and R⁷Independently selected from C_1-6An alkyl group; and

R¹¹Selected from: H. halogen and C_1-6An alkyl group.

Described herein are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein:

is composed of

R¹And R²Independently selected from C_1-6An alkyl group;

R³is-OC (O) NR⁶R⁷；

R⁴Is C_1-10An alkyl group;

R⁶and R⁷Independently selected from C_1-6An alkyl group; and

R¹¹is H.

Described herein are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein:

is composed of

R¹And R²Independently selected from C_1-6An alkyl group;

R³is-OC (O) NR⁶R⁷；

R⁴Is C_1-10An alkyl group;

R⁶and R⁷Independently selected from C_1-6An alkyl group; and

R¹¹is halogen.

Described herein are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein:

is composed of

R¹And R²Independently selected from C_1-6An alkyl group;

R³is-OC (O) NR⁶R⁷；

R⁴Is C_1-10An alkyl group;

R⁶and R⁷Independently selected from C_1-6An alkyl group; and

R¹¹is C_1-6An alkyl group.

Described herein are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein:

is composed of

R¹And R²Independently selected from C_1-6An alkyl group;

R³selected from-N (H) C (O) OR⁵and-OC (O) NR⁶R⁷；

Each R⁴Independently selected from halogen and C_1-10An alkyl group;

R⁵is C_1-6An alkyl group;

R⁶and R⁷Independently selected from C_1-6An alkyl group; and

R¹¹selected from: H. halogen and C_1-6An alkyl group.

Described herein are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein:

Is composed of

R¹And R²Independently selected from C_1-6An alkyl group;

R³is-N (H) C (O) OR⁵；

Each R⁴Independently selected from halogen and C_1-10An alkyl group;

R⁵is C_1-6An alkyl group; and

R¹¹selected from: H. halogen and C_1-6An alkyl group.

Described herein are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein:

is composed of

R¹And R²Independently selected from C_1-6An alkyl group;

R³is-N (H) C (O) OR⁵；

Each R⁴Independently selected from halogen and C_1-10An alkyl group;

R⁵is C_1-6An alkyl group; and

R¹¹is H.

Described herein are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein:

is composed of

R¹And R²Independently selected from C_1-6An alkyl group;

R³is-N (H) C (O) OR⁵；

Each R⁴Independently selected from halogen and C_1-10An alkyl group;

R⁵is C_1-6Alkyl radical(ii) a And

R¹¹is halogen.

Described herein are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein:

is composed of

R¹And R²Independently selected from C_1-6An alkyl group;

R³is-N (H) C (O) OR⁵；

Each R⁴Independently selected from halogen and C_1-10An alkyl group;

R⁵is C_1-6An alkyl group; and

R¹¹is C_1-6An alkyl group.

Described herein are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein:

is composed of

R¹And R²Independently selected from C_1-6An alkyl group;

R³is-OC (O) NR⁶R⁷；

Each R⁴Independently selected from halogen and C_1-10An alkyl group;

R⁶and R⁷Independently selected from C_1-6An alkyl group; and

R¹¹Selected from: H. halogen and C_1-6An alkyl group.

Described herein are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein:

is composed of

R¹And R²Independently selected from C_1-6An alkyl group;

R³is-OC (O) NR⁶R⁷；

Each R⁴Independently selected from halogen and C_1-10An alkyl group;

R⁶and R⁷Independently selected from C_1-6An alkyl group; and

R¹¹is H.

Described herein are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein:

is composed of

R¹And R²Independently selected from C_1-6An alkyl group;

R³is-OC (O) NR⁶R⁷；

Each R⁴Independently selected from halogen and C_1-10An alkyl group;

R⁶and R⁷Independently selected from C_1-6An alkyl group; and

R¹¹is halogen.

Described herein are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein:

is composed of

^R1And R²Independently selected from C_1-6An alkyl group;

R³is-OC (O) NR⁶R⁷；

Each R⁴Independently selected from halogen and C_1-10An alkyl group;

R⁶and R⁷Independently selected from C_1-6An alkyl group; and

R¹¹is C_1-6An alkyl group.

Described herein are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein:

is composed of

R¹And R²Independently selected from C_1-6An alkyl group;

R³selected from-N (H) C (O) OR⁵and-OC (O) NR⁶R⁷；

Each R⁴Independently selected from halogen and C_1-10An alkyl group;

R⁵is C_1-6An alkyl group;

R⁶and R⁷Independently selected from C_1-6An alkyl group; and

R¹¹selected from: H. halogen and C_1-6An alkyl group.

Described herein are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein:

is composed of

R¹And R²Independently selected from C_1-6An alkyl group;

R³is-N (H) C (O) OR⁵；

Each R⁴Independently selected from halogen and C_1-10An alkyl group;

R⁵is C_1-6An alkyl group; and

R¹¹selected from: H. halogen and C_1-6An alkyl group.

Described herein are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein:

is composed of

R¹And R²Independently selected from C_1-6An alkyl group;

R³is-N (H) C (O) OR⁵；

Each R⁴Independently selected from halogen and C_1-10An alkyl group;

R⁵is C_1-6An alkyl group; and

R¹¹is H.

Described herein are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein:

is composed of

R¹And R²Independently selected from C_1-6An alkyl group;

R³is-N (H) C (O) OR⁵；

Each R⁴Independently selected from halogen and C_1-10An alkyl group;

R⁵is C_1-6An alkyl group; and

R¹¹is halogen.

Described herein are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein:

is composed of

R¹And R²Independently selected from C_1-6An alkyl group;

R³is-N (H) C (O) OR⁵；

Each R⁴Independently selected from halogen and C_1-10An alkyl group;

R⁵is C_1-6An alkyl group; and

R¹¹is C_1-6An alkyl group.

Described herein are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein:

is composed of

R¹And R²Independently selected from C _1-6An alkyl group;

R³is-OC (O) NR⁶R⁷；

Each R⁴Independently selected from halogen and C_1-10An alkyl group;

R⁶and R⁷Independently selected from C_1-6An alkyl group; and

R¹¹selected from: H. halogen and C_1-6An alkyl group.

Described herein are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein:

is composed of

R¹And R²Independently selected from C_1-6An alkyl group;

R³is-OC (O) NR⁶R⁷；

Each R⁴Independently selected from halogen and C_1-10An alkyl group;

R⁶and R⁷Independently selected from C_1-6An alkyl group; and

R¹¹is H.

Described herein are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein:

is composed of

R¹And R²Independently selected from C_1-6An alkyl group;

R³is-OC (O) NR⁶R⁷；

Each R⁴Independently selected from halogen and C_1-10An alkyl group;

R⁶and R⁷Independently selected from C_1-6An alkyl group; and

R¹¹is halogen.

Described herein are compounds of formula (IIe), or a pharmaceutically acceptable salt or solvate thereof, wherein:

is composed of

R¹And R²Independently selected from C_1-6An alkyl group;

R³is-OC (O) NR⁶R⁷；

Each R⁴Independently selected from halogen and C_1-10An alkyl group;

R⁶and R⁷Independently selected from C_1-6An alkyl group; and

R¹¹is C_1-6An alkyl group.

Some embodiments are compounds selected from the group consisting of:

2- [ [3- [ [ (E,2S) -7- (dimethylamino) -2- (methoxycarbonylamino) -7-oxo-hept-5-enoyl ] amino ] -2-oxo-1-pyridinyl ] methyl ] -4-isobutyl-benzimidazole-1-carboxylic acid tert-butyl ester;

Methyl N- [ (E,1S) -6- (dimethylamino) -1- [ [1- [ (4-isobutyl-1H-benzimidazol-2-yl) methyl ] -2-oxo-3-pyridinyl ] carbamoyl ] -6-oxo-hex-4-enyl ] carbamate;