Compound (I)

文档序号：1173705 发布日期：2020-09-18 浏览：17次中文

阅读说明：本技术 化合物 (Compound (I) ) 是由 S·科林伍德 C·麦卡锡 J·D·哈格雷夫 D·A·哈伊 T·B·斯科菲尔德 S·埃拉米于 2019-01-25 设计创作，主要内容包括：通式(I)化合物：其中R1、R2、R3、R4、R5a、R5b、X1、X2、Z及Y如本文的定义,其为钙活化氯离子通道(calcium-activated chloride channel,CaCC)正向调节剂,TMEM16A。所述化合物可用于治疗受TMEM16A调节影响的疾病和病症,特别是呼吸系统疾病和病症。<Image he="389" wi="700" file="DDA0002603084150000011.GIF" imgContent="drawing" imgFormat="GIF" orientation="portrait" inline="no"></Image>(A compound of the general formula (I): wherein R is 1 、R 2 、R 3 、R 4 、R 5a 、R 5b 、X 1 、X 2 Z and Y are as defined herein, which are calcium-activated chloride channel (CaCC) positive regulators, TMEM 16A. The compounds are useful for the treatment of diseases and disorders which are affected by modulation of TMEM16A, particularly respiratory diseases and disorders.)

1. Compounds of general formula (I) including all tautomeric forms, all enantiomers and isotopic variations, and salts and solvates thereof:

Wherein:

R¹is H, CN, C (O) OR¹²、C_1-3Alkyl radical, C_2-3Alkenyl or C_2-3Alkynyl, any of which is optionally substituted by one or more substituents, suitably one substituent, selected from: fluorine, OR¹²、N(R¹²)₂、C(O)OR¹²、C(O)N(R¹²)₂、C(O)R¹²And N (R)¹³)C(O)R¹²；

Wherein R is¹²And R¹³Each independently selected from H, C_1-6Alkyl and C_1-6Fluoroalkyl group

R²Is H or C_1-6Alkyl, optionally substituted by OR¹²Substitution;

R³the method comprises the following steps:

C_1-10alkyl radical, C_2-10Alkenyl or C_2-10Alkynyl, any of which is optionally substituted by one or more substituents, suitably one substituent, selected from fluoro, CN, R¹⁴OR¹⁴、OR¹⁵、N(R¹⁵)₂、C(O)OR¹⁵、C(O)N(R¹⁵)₂、N(R¹⁶)C(O)R¹⁵、N(R¹⁵)S(O)₂R¹⁴、N(R¹⁵)S(O)₂R¹⁶And N (R)¹⁵)C(O)OR^16；Or

A 3-to 7-membered carbocyclic or heterocyclic ring system or a 6-to 10-membered aryl or 5-to 10-membered heteroaryl ring system, each of which is optionally substituted with one or more substituents selected from: halo, CN, C_1-4Alkyl radical, C_1-4Haloalkyl, OR¹⁷And N (R)¹⁷)₂；

Wherein R is¹⁴Is a 6-to 10-membered aryl or 5-to 10-membered heteroaryl ring system or a 3-to 7-membered carbocyclic or heterocyclic ring system, any of which is optionally substituted by one or more substituents selected from: halo, C_1-4Alkyl radical, C_1-4Haloalkyl, OR¹⁷And N (R)¹⁷)₂(ii) a Wherein R is¹⁷Each independently is H, C_1-4Alkyl or C_1-4A haloalkyl group;

R¹⁵and R¹⁶Each independently is H, C_1-6Alkyl or C _1-6A haloalkyl group; or

R²And R³Taken together with the carbon atoms to which they are attached form a 3-to 10-membered carbocyclic or heterocyclic ring system, which is optionally substituted with one or more substituents selected from: halo, CN, OR⁹、N(R⁹)₂、C(O)OR⁹、C(O)N(R⁹)₂、C(O)R⁹、N(R⁹)C(O)R⁹And optionally halo, OR⁹Or N (R)⁹)₂Substituted C_1-4An alkyl group; or

R¹、R²And R³Taken together with the carbon atoms to which they are attached form a bridged 5-to 10-membered carbocyclic or heterocyclic ring system or phenyl, any of which is optionally substituted with one or more substituents selected from: halo, CN, OR⁹、N(R⁹)₂、C(O)OR⁹、C(O)N(R⁹)₂、C(O)R⁹、N(R⁹)C(O)R⁹And optionally halo, OR⁹Or N (R)⁹)₂Substituted C_1-4An alkyl group;

R⁹each independently selected from H, C_1-6Alkyl or C_1-6A haloalkyl group;

X¹and X²Each of which is independently N or CR⁸；

R⁸Is H, halo, OH, O (C)_1-4Alkyl), CN or NH₂；

Y being a bond or C being straight-chain_1-6An alkylene chain, optionally substituted by one or more substituents R¹⁸Substituted, in which two substituents R¹⁸May be attached to the same or different carbon atoms;

wherein R is¹⁸Each independently is C_1-3Alkyl or C_1-3Haloalkyl radicals of which-CH₂-is optionally replaced by-NH-or-O-, and wherein two R are¹⁸Groups may combine with one or more of the atoms to which they are attached to form a 3-to 6-membered carbocyclic or heterocyclic ring system;

z is-C (O) -or-C (O) NH-;

R⁴Is a 6-to 14-membered aryl, 5-to 14-membered heteroaryl or 5-to 10-membered carbocyclic ring system, any of which is optionally substituted by one or more substituents selected from:

halo, CN, nitro, R¹⁹、OR¹⁹、OR⁶、SR⁶、NR⁶R⁷、C(O)R⁶、C(O)R¹⁹、C(O)OR⁶、C(O)N(R⁶)(R⁷)、N(R⁷)C(O)R⁶；

C_1-6Alkyl or O (C)_1-6Alkyl), any of which is optionally substituted with one or more substituents selected from: halo, CN, nitro, R¹⁹、OR⁶、SR⁶、NR⁶R⁷、C(O)R⁶C(O)OR⁶、C(O)N(R⁶)(R⁷) And N (R)⁷)C(O)R⁶(ii) a And

oxo radical, when R⁴This is true when not completely aromatic in nature;

wherein R is¹⁹Is a 5-or 6-membered aryl or heteroaryl ring system or a 3-to 7-membered carbocyclic or heterocyclic ring system, any of which is optionally substituted by one or more substituents selected from: halo, C_1-4Alkyl radical, C_1-4Haloalkyl, OH, O (C)_1-4Alkyl), O (C)_1-4Haloalkyl);

R⁶is H, C_1-6Alkyl radical, C_1-6Haloalkyl, benzyl, 3-to 7-membered carbocyclyl or 3-to 7-A heterocyclic group;

R⁷is H, C_1-6Alkyl or C_1-6A haloalkyl group; or

R⁶And R⁷Together with the nitrogen atom to which they are attached may form a 4 to 7-membered heterocyclic ring, optionally containing one or more additional heteroatoms and optionally substituted with one or more substituents selected from oxo and halo; and is

R^5aAnd R^5bIs independently H, C_1-4Alkyl or halo;

it is used in medical applications.

2. A compound for use according to claim 1 for the treatment or prevention of diseases and disorders which are affected by modulation of TMEM 16A.

3. Use of a compound of general formula (I) as defined in claim 1 for the preparation of a medicament for the treatment or prevention of diseases and conditions which are affected by modulation of TMEM 16A.

4. A method of treatment or prevention of diseases and conditions which are affected by modulation of TMEM16A, which method comprises administering to a patient in need of such treatment an effective amount of a compound of general formula (I) as defined in claim 1.

5. The compound for use, the use or the method according to any one of claims 2 to 4, wherein the disease or disorder which is affected by modulation of TMEM16A is selected from respiratory diseases and disorders, dry mouth (xerostomia), intestinal hyperactivity, cholestasis and ocular symptoms.

6. The compound for use, use or method according to claim 5 wherein the respiratory diseases and disorders are selected from the group consisting of cystic fibrosis, Chronic Obstructive Pulmonary Disease (COPD), chronic bronchitis, emphysema, bronchiectasis including non-cystic fibrosis, asthma and primary ciliary dyskinesia.

7. The compound for use, the use or the method according to claim 5, wherein the dry mouth (xerostomia) is caused by sjogren's syndrome, radiotherapy or a drug causing dry mouth.

8. The compound for use, the use or the method according to claim 5, wherein the intestinal hyperactivity is associated with gastric dyspepsia, gastroparesis, chronic constipation or irritable bowel syndrome.

9. The compound for use, the use or the method according to claim 5, wherein the ocular disease is dry eye.

10. A compound, use or method for use according to any one of claims 1 to 9, wherein:

in the compounds of the general formula (I), Z is-C (O) -, and R^5bIs H, such that the compound has formula (IZ):

wherein R is¹、R²、R³、R⁴、R^5a、X¹、X²And Y is as defined in claim 1; or

In the compound of the general formula (I), Z is-C (O) NH-and R^5bIs H, such that the compound has the general formula (Iy):

wherein R is¹、R²、R³、R⁴、R^5a、X¹、X²And Y is as defined in claim 1; or

The compounds of formula (I) are compounds of formula (Ix) including all tautomeric forms, all enantiomers and isotopic variations and salts and solvates thereof:

wherein:

R¹is H, CN or C_1-3Alkyl, optionally substituted with one or more substituents selected from: halo, OR¹²、N(R¹²)₂、C(O)OR¹²、C(O)N(R¹²)₂、C(O)R¹²And N (R)¹³)C(O)R¹²；

Wherein R is¹²And R¹³Each independently selected from H, C_1-6Alkyl or C_1-6A haloalkyl group;

R²is C_1-6An alkyl group;

R³is C_1-6Alkyl, optionally substituted with one or more substituents selected from: halo, OH, O (C) _1-6Alkyl), C (O) O- (C)_1-6Alkyl and N (H) C (O) O- (C)_1-6Alkyl groups); or

R²And R³Taken together with the carbon atoms to which they are attached form a 3-to 10-membered carbocyclic or heterocyclic ring system, which is optionally substituted with one or more substituents selected from: halo, OR⁹、N(R⁹)₂、C(O)OR⁹、C(O)N(R⁹)₂、C(O)R⁹And N (R)⁹)C(O)R⁹(ii) a Or

R¹、R²And R³Taken together with the carbon atoms to which they are attached form a bridged 5-to 10-membered carbocyclic or heterocyclic ring system, which is optionally substituted with one or more substituents selected from: halo, OR⁹、N(R⁹)₂、C(O)OR⁹、C(O)N(R⁹)₂、C(O)R⁹、N(R⁹)C(O)R⁹；

R⁹Each independently selected from H, C_1-6Alkyl or C_1-6A haloalkyl group;

X¹and X²Each of which is independently N or CR⁸；

R⁸Is H, halo, OH,CN or NH₂；

Y is a bond or C_1-6An alkylene group;

R⁴is a 6-10-membered aryl, 5-to 10-membered heteroaryl or a 5-to 10-membered carbocyclic or heterocyclic ring system, any of which is optionally substituted by one or more substituents selected from:

halo, CN, nitro;

OR⁶、SR⁶、NR⁶R⁷、C(O)R⁶C(O)OR⁶、C(O)N(R⁶)(R⁷)、N(R⁷)C(O)R⁶；

C_1-6alkyl, optionally substituted with one or more substituents selected from: halo, CN, nitro, OR⁶、SR⁶、NR⁶R⁷、C(O)R⁶C(O)OR⁶、C(O)N(R⁶)(R⁷) And N (R)⁷)C(O)R⁶(ii) a And is

Oxo radical, when R⁴This is true when not completely aromatic in nature;

wherein R is⁶Is H, C_1-6Alkyl radical, C_1-6Haloalkyl, 3-7 membered carbocyclyl, or 3-7 membered heterocyclyl;

R⁷is H, C_1-6Alkyl or C _1-6A haloalkyl group; or

R⁵Is H, C_1-4Alkyl or halo.

11. The compound, use or method for use according to any one of claims 1 to 10, wherein in the compound of general formula (I), R¹Is H, CN, C (O) OR¹²Or methyl, ethyl or ethynyl, optionally substituted with one or more substituents selected from: fluorine, OR¹²、N(R¹²)₂、C(O)OR¹²、C(O)N(R¹²)₂、C(O)R¹²And N (R)¹³)C(O)R¹²；

Wherein R is¹²And R¹³Each independently as defined in claim 1.

12. The compound, use or method for use according to claim 11, wherein in the compound of general formula (I), R¹Is H, CN, ethynyl or methyl, either of which is unsubstituted or substituted with OH.

13. A compound for use, use or method according to any one of claims 1 to 12, wherein in the compound of general formula (I):

R²is methyl or ethyl; and is

R³Is C_1-4Alkyl, optionally substituted with one or more substituents selected from: hydroxy, methoxy, ethoxy, -C (O) O- (C)_1-4Alkyl) and-N (H) C (O) O- (C)_1-4Alkyl groups); or

R²Is H, methyl or ethyl.

14. A compound for use, use or method according to any one of claims 1 to 13, wherein in the compound of general formula (I):

R³is C_1-10Alkyl or C_2-3Alkynyl, any of which is unsubstituted or substituted with a single substituent selected from: fluorine, R¹⁴OR¹⁴、OR¹⁵、C(O)OR¹⁵、N(R¹⁶)S(O)₂R¹⁵And N (R)¹⁶)C(O)OR¹⁵(ii) a Wherein

R¹⁴Selected from phenyl, pyridyl and 5-or 6-membered heterocycle;

R¹⁵is selected from H or C_1-4An alkyl group; and

R¹⁶is H; or

R³Is a 3-to 7-membered carbocyclic or heterocyclic ring system which is unsubstituted or substituted as defined in claim 1; or

R³Is phenyl or pyridyl, any of whichIs unsubstituted OR substituted by one OR more groups selected from OR¹⁷And N (R)¹⁷)₂Wherein R is¹⁷Each is H or methyl.

15. The compound, use or method for use according to claim 14, wherein in the compound of general formula (I):

R¹is methyl or CN, and R²And R³Are both methyl; or

R²And R³Combine with the carbon atom to which they are attached to form a carbocyclic or heterocyclic ring system, and R¹Is H, methyl, OH-substituted methyl, CN, ethynyl OR C (O) OR¹²Wherein R is¹²As defined in claim 1.

16. A compound for use, use or method according to any one of claims 1 to 15, wherein in the compound of general formula (I):

X¹is N, and X²Is CR⁸Wherein R is ⁸As defined in claim 1; or

X¹And X²Are all CR⁸Wherein R is⁸Each independently as defined in claim 1.

17. A compound for use, use or method according to any one of claims 1 to 16 wherein in the compound of general formula (I) Y is-CH₂-、-CH₂CH₂-、-CH(CH₃)CH₂-、-CH₂CH(CH₃) -or-CH₂CH₂CH₂-。

18. The compound for use, the use or the method according to any one of claims 1 to 17, wherein in the compound of general formula (I), R^5aAnd R^5bAre all H.

19. A compound for use, use or method according to any one of claims 1 to 18, wherein in the compound of general formula (I):

R⁴is a 6-to 11-membered aryl group selected from phenyl, naphthyl, indanyl, 1,2,3, 4-tetrahydronaphthyl and benzocycloheptyl, any of which is optionally substituted as defined in claim 1; or

R⁴Is a 5-to 10-membered heteroaryl group selected from pyridyl, quinolyl, quinoxalinyl, indazolyl, indolyl, benzoxazolyl, dihydrobenzofuranyl, furanyl and thienyl, any of which is optionally substituted as defined in claim 1;

R⁴is carbocyclyl selected from cyclohexyl and adamantyl, any of which is optionally substituted as defined in claim 1; or

R⁴Is phenyl, optionally substituted with one or more substituents as defined in claim 1; or

R⁴Is a 5-10-membered heteroaryl group selected from pyridyl, pyrrolyl, thienyl, furyl, benzoxazolyl, imidazolyl, indolyl or indazolyl, any of which is optionally substituted as defined in claim 1.

20. A compound for use, use or method according to any one of claims 1 to 19 wherein in the compound of general formula (I) Y is-CH₂-，R⁴Is phenyl and the compound is of the general formula (Ia):

wherein

R¹、R²、R³、R^5a、X¹And X²As defined in claim 1;

R¹⁰is H, OH, halo, C_1-6Alkyl, -O (C)_1-6Alkyl groups);

R¹¹each independently of the others being H, halo, OH, CN, C_1-6Alkyl radical, C_1-6Haloalkyl, -O (C)_1-6Alkyl) or C (O) O- (C)_1-6Alkyl groups); and is

n is 1 or 2.

21. The compound, use or method for use according to claim 20, wherein the compound of formula (I) is a compound of formula (Ib) or (Ic):

wherein

R¹、R²、R³、R^5a、X¹And X²As defined in claim 1;

R^11ais H, halo, C_1-4Alkyl radical, C_1-4Haloalkyl or C (O) O (C)_1-4Alkyl groups);

R^11bis H, halo, C_1-4Alkyl or C_1-4A haloalkyl group;

R^11cis H, halo, CN, C_1-4Alkyl or C_1-4A haloalkyl group; or

The compound of the general formula (I) is a compound of the general formula (Id) or (Ie):

wherein R is¹、R²、R³、R^11a、R^11bAnd R^11cAs defined above for the compounds of the general formulae (Ib) and (Ic).

22. A compound for use, use or method according to any one of claims 1 to 9 wherein the compound of general formula (I) is selected from:

n-tert-butyl-4- [ [2- (2-hydroxyphenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 1);

n- (1, 1-dimethylpropyl) -3- [ [2- (2-hydroxyphenyl) acetyl ] amino ] benzamide (compound 1.1);

n- (1-adamantyl) -3- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] benzamide (compound 1.2);

n- (1-adamantyl) -4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 1.3);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (3-methoxy-1, 1-dimethyl-propyl) pyridine-2-carboxamide (compound 1.4);

3- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (1, 1-dimethylpropyl) benzamide (compound 1.5);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (1-methylcyclobutyl) pyridine-2-carboxamide (compound 1.6);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (1-methylcyclohexyl) pyridine-2-carboxamide (compound 1.7);

n- [3- [ [4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carbonyl ] amino ] -3-methyl-butyl ] carbamic acid tert-butyl ester (compound 1.8);

3- [ [2- (2-hydroxyphenyl) acetyl ] amino ] -N- (2-methoxy-1, 1-dimethyl-ethyl) benzamide (compound 1.9);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N-cyclohexyl-pyridine-2-carboxamide (compound 1.10);

n-tert-butyl-3- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] benzamide (compound 2);

n-tert-butyl-3- [ [2- (5-fluoro-2-hydroxy-phenyl) acetyl ] amino ] benzamide (compound 2.1);

n-tert-butyl-3- [ [2- (3-fluoro-2-hydroxy-phenyl) acetyl ] amino ] benzamide (compound 2.2);

n-tert-butyl-3- [ [2- (4-fluoro-2-hydroxy-phenyl) acetyl ] amino ] benzamide (compound 2.3);

n-tert-butyl-3- [ [2- (2, 6-dihydroxyphenyl) acetyl ] amino ] benzamide (compound 2.4);

n-tert-butyl-3- [3- (2-hydroxyphenyl) propionylamino ] benzamide (compound 2.5);

n-tert-butyl-3- [ [2- (2-hydroxy-6-methoxy-phenyl) acetyl ] amino ] benzamide (compound 2.6);

n-tert-butyl-3- [2- (2-hydroxyphenyl) propionylamino ] benzamide (compound 2.7);

n-tert-butyl-3- [ [2- (2-hydroxy-3-methoxy-phenyl) acetyl ] amino ] benzamide (compound 2.8);

n-tert-butyl-3- [ [2- (3, 5-difluoro-2-hydroxy-phenyl) acetyl ] amino ] benzamide (compound 2.9);

3- [ [2- (5-bromo-2-hydroxy-phenyl) acetyl ] amino ] -N-tert-butyl-benzamide (compound 2.10);

n-tert-butyl-3- [ [2- (2, 3-difluoro-6-hydroxy-phenyl) acetyl ] amino ] benzamide (compound 2.11);

n-tert-butyl-3- [ [2- (4, 5-difluoro-2-hydroxy-phenyl) acetyl ] amino ] benzamide (compound 2.12);

n- (1, 1-dimethylpropyl) -3- [ [2- (4-fluoro-2-hydroxy-phenyl) acetyl ] amino ] benzamide (compound 2.13);

n-tert-butyl-3- [ [2- (2-hydroxy-4-methoxy-phenyl) acetyl ] amino ] benzamide (compound 2.14);

n-tert-butyl-3- [ [2- (2-fluoro-6-hydroxy-phenyl) acetyl ] amino ] benzamide (compound 2.15);

n-tert-butyl-3- [ [2- (2, 3-dihydroxyphenyl) acetyl ] amino ] benzamide (compound 2.16);

n-tert-butyl-3- [ [2- [ 2-hydroxy-5- (trifluoromethyl) phenyl ] acetyl ] amino ] benzamide (compound 2.17);

3- [2- [3- (tert-butylcarbamoyl) anilino ] -2-oxo-ethyl ] -4-hydroxy-benzoic acid methyl ester (Compound 2.18);

n-tert-butyl-3- [ [2- [ 2-hydroxy-4- (trifluoromethyl) phenyl ] acetyl ] amino ] benzamide (compound 2.19);

n-tert-butyl-4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 3);

N- (1, 1-dimethylpropyl) -4- [ [2- (4-fluoro-2-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 3.1 a); n-tert-butyl-4- [ [2- (4-fluoro-2-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 3.2 a);

n-tert-butyl-4- [ [2- (2-chloro-6-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 3.3 a);

4- [ [2- (4-bromo-5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N-tert-butyl-pyridine-2-carboxamide (compound 3.4 a);

4- [ [2- (5-tert-butyl-2-hydroxy-phenyl) acetyl ] amino ] -N- (1-cyanocyclobutyl) pyridine-2-carboxamide (compound 3.5 a);

4- [ [2- (5-tert-butyl-2-hydroxy-phenyl) acetyl ] amino ] -N- (1-methylcyclobutyl) pyridine-2-carboxamide (compound 3.6 a);

n-tert-butyl-4- [2- (2, 5-dibromo-3-fluoro-6-hydroxyphenyl) acetylamino ] pyridine-2-carboxamide (Compound 3.7 a);

n-tert-butyl-4- [ [2- [ 2-hydroxy-5- (trifluoromethyl) phenyl ] acetyl ] amino ] pyridine-2-carboxamide (compound 3.5 b);

n-tert-butyl-4- [ [2- (4-chloro-2-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 3.6 b);

n-tert-butyl-4- [ [2- [ 2-hydroxy-4- (trifluoromethyl) phenyl ] acetyl ] amino ] pyridine-2-carboxamide (compound 3.7 b);

N-tert-butyl-4- [ [2- (2-hydroxy-5-methoxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 3.8 b);

n-tert-butyl-4- [ (6-hydroxyindan-1-carbonyl) amino ] pyridine-2-carboxamide (Compound 3.9 b);

n-tert-butyl-4- [ (7-hydroxyindan-1-carbonyl) amino ] pyridine-2-carboxamide (Compound 3.10 b);

n-tert-butyl-4- [ [2- (2, 5-dibromo-3-chloro-6-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 3.11 b);

n-tert-butyl-4- [ [2- (3-hydroxyphenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 3.12 b);

n-tert-butyl-4- [ [2- (2-fluoro-5-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 3.13 b);

n-tert-butyl-4- [ [2- (4-chloro-3-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 3.14 b);

n-tert-butyl-4- [ [2- (2-chloro-3-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 3.15 b);

n-tert-butyl-4- [ [2- (2-chloro-5-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 3.16 b);

n-tert-butyl-4- [ [2- (3-chloro-5-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 3.17 b);

n-tert-butyl-3- [ [2- (3-hydroxyphenyl) acetyl ] amino ] benzamide (compound 4);

N-tert-butyl-3- [ [2- (1H-indazol-3-yl) acetyl ] amino ] benzamide (compound 4.1);

n-tert-butyl-3- [ [2- (5-fluoro-1H-indol-3-yl) acetyl ] amino ] benzamide (compound 4.2);

n-tert-butyl-3- [ [2- (2-hydroxyphenyl) acetyl ] amino ] benzamide (compound 4.3);

n-tert-butyl-3- [ [2- (7-fluoro-2-methyl-1H-indol-3-yl) acetyl ] amino ] benzamide (compound 4.4);

n-tert-butyl-3- [ [2- (1H-indol-3-yl) acetyl ] amino ] benzamide (compound 4.5);

n-tert-butyl-3- [ (2-phenylacetyl) amino ] benzamide (compound 4.6);

n-tert-butyl-3- [ [2- (2-fluoro-6-methoxy-phenyl) acetyl ] amino ] benzamide (compound 4.7);

n-tert-butyl-3- [ [2- (2, 3-difluoro-6-methoxy-phenyl) acetyl ] amino ] benzamide (compound 4.8);

n-tert-butyl-3- [ [2- [ 2-methoxy-4- (trifluoromethyl) phenyl ] acetyl ] amino ] benzamide (compound 4.9);

n-tert-butyl-4- [ [2- (2-thienyl) acetyl ] amino ] pyridine-2-carboxamide (compound 5);

4- [ [2- (2-adamantyl) acetyl ] amino ] -N-tert-butyl-pyridine-2-carboxamide (compound 5.1);

n-tert-butyl-4- [ [2- (4-fluoro-2-methoxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 5.2);

N-tert-butyl-4- [ [2- (5-chloro-2-fluoro-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 5.3);

n-tert-butyl-4- [ [2- (2-furanyl) acetyl ] amino ] pyridine-2-carboxamide (compound 5.4);

n-tert-butyl-4- [ [2- (3-chlorophenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 5.5);

n-tert-butyl-4- [ [2- (1H-indol-3-yl) acetyl ] amino ] pyridine-2-carboxamide (compound 5.6);

n-tert-butyl-4- [ [2- (o-tolyl) acetyl ] amino ] pyridine-2-carboxamide (compound 5.7);

n-tert-butyl-4- [ [2- (3, 4-dichlorophenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 5.8);

n-tert-butyl-4- [ [2- (3-fluorophenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 5.9);

n-tert-butyl-4- [ [2- (5-chloro-2-methoxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 5.10);

n-tert-butyl-4- [ [2- (p-tolyl) acetyl ] amino ] pyridine-2-carboxamide (compound 5.11);

n-tert-butyl-4- [ [2- (2-fluorophenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 5.12);

n-tert-butyl-4- [ [2- (4-fluorophenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 5.13);

n-tert-butyl-4- [ [2- (m-tolyl) acetyl ] amino ] pyridine-2-carboxamide (compound 5.14);

4- [ [2- (1, 3-benzoxazol-6-yl) acetyl ] amino ] -N-tert-butyl-pyridine-2-carboxamide (compound 5.15);

n-tert-butyl-4- [ [2- (2-chloro-3-pyridinyl) acetyl ] amino ] pyridine-2-carboxamide (compound 5.16);

n-tert-butyl-4- [ [2- (2, 6-dichlorophenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 5.17);

n-tert-butyl-4- [ [2- (4-chloro-3-fluoro-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 5.18);

n-tert-butyl-4- [ [2- (3, 5-dichlorophenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 5.19);

n-tert-butyl-4- [ [2- (2-chlorophenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 5.20);

n-tert-butyl-4- [ [2- (3-chloro-4-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 5.21);

n-tert-butyl-4- (indan-1-carbonylamino) pyridine-2-carboxamide (compound 5.22);

n-tert-butyl-4- [ (2-quinoxalin-6-ylacetyl) amino ] pyridine-2-carboxamide (Compound 5.23);

n-tert-butyl-4- [ [2- (2-naphthyl) acetyl ] amino ] pyridine-2-carboxamide (compound 5.24);

n-tert-butyl-4- (2, 3-dihydrobenzofuran-3-carbonylamino) pyridine-2-carboxamide (compound 5.25);

n-tert-butyl-4- (6,7,8, 9-tetrahydro-5H-benzo [7] annulene-5-carbonylamino) pyridine-2-carboxamide (Compound 5.26);

N-tert-butyl-4- (1,2,3, 4-tetrahydronaphthalene-1-carbonylamino) pyridine-2-carboxamide (compound 5.27);

n-tert-butyl-4- [ [2- (6-quinolinyl) acetyl ] amino ] pyridine-2-carboxamide (compound 5.29);

n-tert-butyl-4- [ [1- (3-chlorophenyl) cyclopropanecarbonyl ] amino ] pyridine-2-carboxamide (compound 5.31);

n-tert-butyl-4- [ [2- (2, 3-dihydro-1, 4-benzodioxine-6-yl) acetyl ] amino ] pyridine-2-carboxamide (compound 5.32);

n- (1, 1-dimethylprop-2-ynyl) -4- [ (2-isochroman-1-ylacetyl) amino ] pyridine-2-carboxamide (compound 5.33);

4- [ [2- (4, 4-difluorocyclohexyl) acetyl ] amino ] -N- (1, 1-dimethylprop-2-ynyl) pyridine-2-carboxamide (compound 5.34);

n- (1, 1-dimethylprop-2-ynyl) -4- [ [2- [4- (trifluoromethyl) phenyl ] acetyl ] amino ] pyridine-2-carboxamide (compound 5.35);

n- (1, 1-dimethylprop-2-ynyl) -4- [ [2- [3- (trifluoromethyl) -1H-pyrazol-4-yl ] acetyl ] amino ] pyridine-2-carboxamide (compound 5.36);

n- (1, 1-dimethylprop-2-ynyl) -4- [ [2- [3- (trifluoromethyl) phenyl ] acetyl ] amino ] pyridine-2-carboxamide (compound 5.37);

n- (1, 1-dimethylprop-2-ynyl) -4- [ [2- [2- (trifluoromethyl) phenyl ] acetyl ] amino ] pyridine-2-carboxamide (compound 5.38);

4- [ [2- (2, 3-dihydro-1, 4-benzoxazin-4-yl) acetyl ] amino ] -N- (1, 1-dimethylprop-2-ynyl) pyridine-2-carboxamide (compound 5.39);

n-tert-butyl-4- [ [2- (5-cyano-2-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 6);

3- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (1,1,2, 2-tetramethylpropyl) benzamide (compound 7);

3- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (1, 1-dimethylbutyl) benzamide (compound 7.1);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (1, 1-dimethylbutyl) pyridine-2-carboxamide (compound 7.2);

3- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N-cyclohexyl-benzamide (compound 7.3);

3- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N-tetrahydropyran-4-yl-benzamide (compound 7.4);

3- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (1,1, 2-trimethylpropyl) benzamide (compound 7.5);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (1,1, 2-trimethylpropyl) pyridine-2-carboxamide (compound 7.6);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N-isopropyl-pyridine-2-carboxamide (compound 7.7);

3- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (4-methyltetrahydropyran-4-yl) benzamide (compound 7.8);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (4-methyltetrahydropyran-4-yl) pyridine-2-carboxamide (compound 7.9);

3- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (1-methylcyclobutyl) benzamide (compound 7.10);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N-tetrahydropyran-4-yl-pyridine-2-carboxamide (compound 7.11);

4- [2- (5-chloro-2-hydroxyphenyl) acetylamino ] -N- [ (1s,4s) -4-hydroxycyclohexyl ] pyridine-2-carboxamide (compound 7.12);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N-sec-butyl-pyridine-2-carboxamide (compound 7.13);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (2-hydroxy-1, 1, 2-trimethyl-propyl) pyridine-2-carboxamide (compound 7.14);

n- (3-bicyclo [1.1.1] pentyl) -4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 7.15);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (1-cyanocyclobutyl) pyridine-2-carboxamide (compound 7.16);

3- [ [3- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] benzoyl ] amino ] piperidine-1-carboxylic acid tert-butyl ester (compound 8);

3- [ [4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carbonyl ] amino ] piperidine-1-carboxylic acid tert-butyl ester (compound 8.1);

4- [ [3- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] benzoyl ] amino ] -4-methyl-piperidine-1-carboxylic acid tert-butyl ester (compound 8.2);

(1r,5s,6s) -6- {4- [2- (5-chloro-2-hydroxyphenyl) acetylamino ] pyridin-2-amido } -3-azabicyclo [3.1.0] hexane-3-carboxylic acid tert-butyl ester (compound 8.3);

n-tert-butyl-3- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -4-fluoro-benzamide (compound 9);

n-tert-butyl-3- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -5-methyl-benzamide (compound 9.1);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (1, 1-dimethylpropyl) pyridine-2-carboxamide (compound 9.2);

n-tert-butyl-4- [ [2- (5-tert-butyl-2-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 10);

n-tert-butyl-5- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -2-hydroxy-benzamide (compound 11);

n-tert-butyl-3- [ [2- (5-cyano-2-hydroxy-phenyl) acetyl ] amino ] benzamide (compound 12);

3- [2- [ [2- (tert-butylcarbamoyl) -4-pyridinyl ] amino ] -2-oxo-ethyl ] -4-hydroxy-benzoic acid methyl ester (compound 13);

n-tert-butyl-3- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -4-hydroxy-benzamide (compound 14);

N-tert-butyl-4- [ [2- (2-hydroxy-5-methyl-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 15);

n-tert-butyl-3- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -4-methoxy-benzamide (compound 16);

n-tert-butyl-5- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -2-fluoro-benzamide (compound 17);

n-tert-butyl-3- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -5-fluoro-benzamide (compound 18);

n-tert-butyl-4- [ [2- (3-hydroxy-2-pyridinyl) acetyl ] amino ] pyridine-2-carboxamide (compound 19);

n-tert-butyl-4- [ [2- (5-fluoro-2-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 20);

n-tert-butyl-4- [ [ (1R) or (1S) -indan-1-carbonyl ] amino ] pyridine-2-carboxamide (compound 21 a);

n-tert-butyl-4- [ [ (1R) or (1S) -indan-1-carbonyl ] amino ] pyridine-2-carboxamide (compound 21 b);

n-tert-butyl-4- [ (2-phenylacetyl) amino ] pyridine-2-carboxamide (compound 22);

4- (3, 3-dimethylbutyrylamino) -N- (1, 1-dimethylprop-2-ynyl) pyridine-2-carboxamide (compound 22.1);

4- [ (2-Cyclopentylacetyl) amino ] -N- (1, 1-dimethylprop-2-ynyl) pyridine-2-carboxamide (Compound 22.2);

4- [ [2- (3-chloro-4-pyridinyl) acetyl ] amino ] -N- (1, 1-dimethylprop-2-ynyl) pyridine-2-carboxamide (compound 22.3);

4- [ [2- (4-chlorophenyl) acetyl ] amino ] -N- (1-cyanocyclopropyl) pyridine-2-carboxamide (compound 23);

4- [ [2- (3-chlorophenyl) acetyl ] amino ] -N- (1-cyanocyclopropyl) pyridine-2-carboxamide (compound 23.1);

4- [ [2- (2-chloro-5-fluoro-phenyl) acetyl ] amino ] -N- (1-cyanocyclopropyl) pyridine-2-carboxamide (compound 23.2);

n-tert-butyl-4- (indan-2-carbonylamino) pyridine-2-carboxamide (compound 23.3);

n-tert-butyl-4- [ [2- [2- (difluoromethoxy) phenyl ] acetyl ] amino ] pyridine-2-carboxamide (compound 23.4);

n-tert-butyl-4- [ [2- [2- (difluoromethyl) phenyl ] acetyl ] amino ] pyridine-2-carboxamide (compound 23.5);

n-tert-butyl-4- [ [2- (3, 4-difluorophenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 23.6);

n-tert-butyl-4- [ [2- (3, 5-difluorophenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 23.7);

n-tert-butyl-4- [ [2- (2, 3-difluorophenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 23.8);

4- [ [2- (2-chlorophenyl) acetyl ] amino ] -N-tetrahydropyran-4-yl-pyridine-2-carboxamide (compound 23.9);

n- (1-cyanocyclobutyl) -4- [ [2- (6-quinolinyl) acetyl ] amino ] pyridine-2-carboxamide (compound 23.11);

n-tert-butyl-4- [ [2- [2- (trifluoromethyl) phenyl ] acetyl ] amino ] pyridine-2-carboxamide (compound 23.12);

4- [ [2- (2-bromophenyl) acetyl ] amino ] -N-tert-butyl-pyridine-2-carboxamide (compound 23.13);

n-tert-butyl-4- [ [2- (2-cyanophenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 23.14);

4- [ [2- (2-chlorophenyl) acetyl ] amino ] -N- (4-cyanotetrahydropyran-4-yl) pyridine-2-carboxamide (compound 23.15);

n- (4-cyanotetrahydropyran-4-yl) -4- [ [2- (6-quinolinyl) acetyl ] amino ] pyridine-2-carboxamide (compound 23.16);

4- [ [2- (2-chloro-5-methoxy-phenyl) acetyl ] amino ] -N- (1-cyanocyclopropyl) pyridine-2-carboxamide (compound 24);

n- (3-bicyclo [1.1.1] pentyl) -4- [ [2- (5-tert-butyl-2-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 25);

- [ [2- (5-tert-butyl-2-hydroxy-phenyl) acetyl ] amino ] -N- (4-cyanotetrahydropyran-4-yl) pyridine-2-carboxamide (compound 25.1);

n-tert-butyl-4- [ [2- (2-hydroxy-5-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 26);

n-tert-butyl-4- [ [2- [ 5-chloro-2-hydroxy-4- (pyrrolidin-1-ylmethyl) phenyl ] acetyl ] amino ] pyridine-2-carboxamide (compound 27);

n-tert-butyl-4- [ [2- [4- [ (tert-butylamino) methyl ] -5-chloro-2-hydroxy-phenyl ] acetyl ] amino ] pyridine-2-carboxamide (compound 27.1);

N-tert-butyl-4- [ [2- [ 5-chloro-2-hydroxy-4- (morpholinomethyl) phenyl ] acetyl ] amino ] pyridine-2-carboxamide (compound 27.2);

n-tert-butyl-4- [ [2- [ 5-chloro-4- [ (3, 3-difluoropyrrolidin-1-yl) methyl ] -2-hydroxy-phenyl ] acetyl ] amino ] pyridine-2-carboxamide (compound 27.3);

n-tert-butyl-4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -5-fluoro-pyridine-2-carboxamide (compound 28);

n-tert-butyl-4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -3-fluoro-pyridine-2-carboxamide (compound 28.1);

4- [ [2- (2-chlorophenyl) acetyl ] amino ] -N- (1-cyanocyclobutyl) pyridine-2-carboxamide (compound 30);

4- [ [2- (2-chlorophenyl) acetyl ] amino ] -N- (1, 1-dimethylprop-2-ynyl) pyridine-2-carboxamide (compound 30.1);

4- [ [2- (2-chlorophenyl) acetyl ] amino ] -N- (4-fluoro-1-bicyclo [2.1.1] hexyl) pyridine-2-carboxamide (compound 30.2);

4- [ [2- (2-chlorophenyl) acetyl ] amino ] -N- (1-cyclopropyl-1-methyl-ethyl) pyridine-2-carboxamide (compound 30.3);

4- [ [2- (2-chlorophenyl) acetyl ] amino ] -N- (1-cyano-1-methyl-ethyl) pyridine-2-carboxamide (compound 30.3 a);

4- [ [2- (2-chlorophenyl) acetyl ] amino ] -N- (1-methyl-3-bicyclo [1.1.1] pentyl) pyridine-2-carboxamide (compound 30.4);

4- [ [2- (2-chlorophenyl) acetyl ] amino ] -N- (1-cyano-3-bicyclo [1.1.1] pentyl) pyridine-2-carboxamide (compound 30.5);

4- [ [2- (2-chlorophenyl) acetyl ] amino ] -N- (2, 2-difluorocyclopropyl) pyridine-2-carboxamide (compound 30.6);

4- [ [2- (2-chlorophenyl) acetyl ] amino ] -N- (1-cyanocyclopropyl) pyridine-2-carboxamide (compound 30.7);

4- [ [2- (2-chlorophenyl) acetyl ] amino ] -N- (1-methylcyclopropyl) pyridine-2-carboxamide (compound 30.8);

4- [ [2- (2-chlorophenyl) acetyl ] amino ] -N- (3-fluoro-1-bicyclo [1.1.1] pentyl) pyridine-2-carboxamide (compound 30.9);

4- [ [2- (2-chlorophenyl) acetyl ] amino ] -N- (2-fluoro-1, 1-dimethyl-ethyl) pyridine-2-carboxamide (compound 30.10);

4- [ [2- (2-chlorophenyl) acetyl ] amino ] -N- (4-ethynyltetrahydropyran-4-yl) pyridine-2-carboxamide (compound 30.11);

4- [ [2- (2-chlorophenyl) acetyl ] amino ] -N- (1-cyanocyclopentyl) pyridine-2-carboxamide (compound 30.12);

4- [ [2- (2-chlorophenyl) acetyl ] amino ] -N- (2, 2-difluoro-1, 1-dimethyl-ethyl) pyridine-2-carboxamide (compound 30.13);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (4-cyanotetrahydropyran-4-yl) pyridine-2-carboxamide (compound 31);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (1-ethynylcyclopentyl) pyridine-2-carboxamide (compound 31.2);

4- [2- (5-chloro-2-hydroxyphenyl) acetylamino ] -N- [ (1s,2s) -2-hydroxycyclohexyl ] pyridine-2-carboxamide (compound 31.3);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [ (1S,2S) -2-hydroxycyclohexyl ] pyridine-2-carboxamide or 4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [ (1R,2R) -2-hydroxycyclohexyl ] pyridine-2-carboxamide (compound 31.3 a);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (4-ethynyl-tetrahydro-pyran-4-yl) pyridine-2-carboxamide (compound 31.4);

n- [ (6-amino-2-pyridinyl) methyl ] -4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 32);

12- [ [4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carbonyl ] amino ] dodecanoic acid (compound 32.1);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (3-pyridylmethyl) pyridine-2-carboxamide (compound 32.2);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (2-pyridylmethyl) pyridine-2-carboxamide (compound 32.3);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (4-pyridylmethyl) pyridine-2-carboxamide (compound 32.4);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [ (2-hydroxyphenyl) methyl ] pyridine-2-carboxamide (compound 32.5);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (1, 1-dimethyl-2-morpholino-ethyl) pyridine-2-carboxamide (compound 32.6);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (2-hydroxy-1, 1-dimethyl-ethyl) pyridine-2-carboxamide (compound 32.7);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (3, 3-difluoro-4-piperidinyl) pyridine-2-carboxamide (compound 32.8);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (1H-imidazol-2-yl) pyridine-2-carboxamide (compound 32.9);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [ (1R,2R) -2-hydroxycyclopentyl ] pyridine-2-carboxamide (compound 33);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (1-cyano-1-methyl-ethyl) pyridine-2-carboxamide (compound 34);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [3- (hydroxymethyl) tetrahydrofuran-3-yl ] pyridine-2-carboxamide (compound 35);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [ (3R) -3- (hydroxymethyl) tetrahydrofuran-3-yl ] pyridine-2-carboxamide or

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [ (3S) -3- (hydroxymethyl) tetrahydrofuran-3-yl ] pyridine-2-carboxamide (compound 35 a);

- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [ (3R) -3- (hydroxymethyl) tetrahydrofuran-3-yl ] pyridine-2-carboxamide or

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [ (3S) -3- (hydroxymethyl) tetrahydrofuran-3-yl ] pyridine-2-carboxamide (compound 35 b);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (4-hydroxy-4-methyl-cyclohexyl) pyridine-2-carboxamide as a mixture of stereoisomers of 6:4 (compound 35.1);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [ (1s,2r) -2- (hydroxymethyl) cyclohexyl ] pyridine-2-carboxamide (compound 35.2);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [ (1s,3r) -3-hydroxycyclopentyl ] pyridine-2-carboxamide (compound 35.3);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [ 2-hydroxy-1- (hydroxymethyl) -1-methyl-ethyl ] pyridine-2-carboxamide (compound 35.4);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (3-hydroxycyclohexyl) pyridine-2-carboxamide as a mixture of stereoisomers (compound 35.6);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (3-phenoxypropyl) pyridine-2-carboxamide (compound 35.7);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (1-methylcyclopropyl) pyridine-2-carboxamide (compound 35.8);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [ 1-methyl-1- (2-pyridinyl) ethyl ] pyridine-2-carboxamide (compound 35.9);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (3-phenylpropyl) pyridine-2-carboxamide (compound 35.10);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [ 2-hydroxy-1- (2-pyridinyl) ethyl ] pyridine-2-carboxamide (compound 35.11);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [ (5-methoxy-2-pyridinyl) methyl ] pyridine-2-carboxamide (compound 35.12);

3- [ [4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carbonyl ] amino ] -3-methyl-butyric acid ethyl ester (compound 35.13);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (3-hydroxy-1, 1-dimethyl-propyl) pyridine-2-carboxamide (compound 35.14);

n-benzyl-4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 35.15);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N-phenyl-pyridine-2-carboxamide (compound 35.16);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [ (1S,2S) -2-hydroxycyclopentyl ] pyridine-2-carboxamide (compound 35.17);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [ (1R,2S) -2-hydroxycyclopentyl ] pyridine-2-carboxamide (compound 35.18);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [ (1S,2R) -2-hydroxycyclopentyl ] pyridine-2-carboxamide (compound 35.19);

3- [ [2- (5-fluoro-2-hydroxy-phenyl) acetyl ] amino ] -N- (1-methylcyclohexyl) benzamide (compound 35.20);

n- (1, 1-dimethylprop-2-ynyl) -3- [ [2- (5-fluoro-2-hydroxy-phenyl) acetyl ] amino ] benzamide (compound 35.21);

n-cyclohexyl-3- [ [2- (5-fluoro-2-hydroxy-phenyl) acetyl ] amino ] benzamide (compound 35.22);

3- [ [2- (5-fluoro-2-hydroxy-phenyl) acetyl ] amino ] -N- [3- (hydroxymethyl) tetrahydrofuran-3-yl ] benzamide (compound 35.23);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (1-ethynylcyclohexyl) pyridine-2-carboxamide (compound 35.24);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [1- (hydroxymethyl) cyclobutyl ] pyridine-2-carboxamide (compound 35.25);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [3- (hydroxymethyl) oxetan-3-yl ] pyridine-2-carboxamide (compound 35.26);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (1-cyano-2-methoxy-1-methyl-ethyl) pyridine-2-carboxamide (compound 35.27);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [ (1-hydroxycyclobutyl) methyl ] pyridine-2-carboxamide (compound 35.28);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (1, 1-dimethylprop-2-ynyl) pyridine-2-carboxamide (compound 36);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (1-cyano-1, 2-dimethyl-propyl) pyridine-2-carboxamide (compound 37);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (1-methylcyclopentyl) pyridine-2-carboxamide (compound 38);

n- (4-tert-butylcyclohexyl) -4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 39);

n-tert-butyl-4- [ [2- (2-chloro-3-fluoro-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 40);

n-tert-butyl-4- [ [2- (2-chloro-5-fluoro-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 40.1);

n- (4-cyanotetrahydropyran-4-yl) -3- [ [2- (5-fluoro-2-hydroxy-phenyl) acetyl ] amino ] benzamide (compound 41);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [4- (2-hydroxyethyl) tetrahydropyran-4-yl ] pyridine-2-carboxamide (compound 42);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [1, 1-dimethyl-3- (2,2, 2-trifluoroethylamino) propyl ] pyridine-2-carboxamide (compound 43);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (4-fluoro-1-bicyclo [2.1.1] hexyl) pyridine-2-carboxamide (compound 44);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [3- (2, 2-dimethylpropanoylamino) -1, 1-dimethyl-propyl ] pyridine-2-carboxamide (compound 45);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (1-cyano-2-hydroxy-1-methyl-ethyl) pyridine-2-carboxamide (compound 46);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [ (1S) -1-cyano-2-hydroxy-1-methyl-ethyl ] pyridine-2-carboxamide or

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [ (1R) -1-cyano-2-hydroxy-1-methyl-ethyl ] pyridine-2-carboxamide (compound 46 a);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [ (1S) -1-cyano-2-hydroxy-1-methyl-ethyl ] pyridine-2-carboxamide or

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [ (1R) -1-cyano-2-hydroxy-1-methyl-ethyl ] pyridine-2-carboxamide (compound 46 b);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (3-cyanotetrahydrofuran-3-yl) pyridine-2-carboxamide (compound 47);

methyl 2- [4- [ [4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carbonyl ] amino ] tetrahydropyran-4-yl ] acetate (compound 47.1);

4- [ [4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carbonyl ] amino ] tetrahydropyran-4-carboxylic acid methyl ester (compound 47.2);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (3-cyanooxetan-3-yl) pyridine-2-carboxamide (compound 47.3);

4- [ [2- (5-fluoro-2-hydroxy-phenyl) acetyl ] amino ] -N- (1-methylcyclobutyl) pyridine-2-carboxamide (compound 48);

n- (4-cyanotetrahydropyran-4-yl) -4- [ [2- (5-fluoro-2-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 48.1);

n- [3- (tert-butylamino) -1, 1-dimethyl-3-oxo-propyl ] -4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 49);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [3- (methylsulfonylamino) -1, 1-dimethyl-propyl ] pyridine-2-carboxamide (compound 50);

n- (3-acetylamino-1, 1-dimethyl-propyl) -4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 51);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [4- (hydroxymethyl) tetrahydropyran-4-yl ] pyridine-2-carboxamide (compound 53);

n-tert-butyl-4- [ [2- [3- (1-hydroxyethyl) phenyl ] acetyl ] amino ] pyridine-2-carboxamide (compound 54);

n-tert-butyl-5-chloro-4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 55);

N-tert-butyl-4- [ [2- [ 5-chloro-2- [ (4-methoxyphenyl) methoxy ] phenyl ] acetyl ] amino ] pyridine-2-carboxamide (compound 56);

n-tert-butyl-4- [ [ (1S) or (1R) -4-chloro-7-hydroxy-indan-1-carbonyl ] amino ] pyridine-2-carboxamide and example 57 b: n-tert-butyl-4- [ [ (1S) or (1R) -4-chloro-7-hydroxy-indan-1-carbonyl ] amino ] pyridine-2-carboxamide (compound 57 a);

n-tert-butyl-4- [ [2- (2-cyclopropylphenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 58);

4- [ [2- (3-bromo-5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N-tert-butyl-pyridine-2-carboxamide (compound 59);

n- (4-fluoro-1-bicyclo [2.1.1] hexyl) -4- [ [2- (2-fluorophenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 60);

n- (1-cyano-2-hydroxy-1-methyl-ethyl) -4- [ [2- (2-fluorophenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 60.1);

n- (1, 1-dimethylprop-2-ynyl) -4- [ [2- (2-fluorophenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 60.2);

N-tert-butyl-4- [ [2- (5-chloro-2-hydroxy-3-isopropyl-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 61);

n-tert-butyl-4- [ [2- [ 5-chloro-2-hydroxy-3- (1-methoxyethyl) phenyl ] acetyl ] amino ] pyridine-2-carboxamide (compound 62);

4- [ [2- (6-quinolinyl) acetyl ] amino ] -N-tetrahydropyran-4-yl-pyridine-2-carboxamide (compound 63);

4- (benzylcarbamoylamino) -N-tert-butyl-pyridine-2-carboxamide (compound 64);

n-tert-butyl-4- (cyclohexylmethylcarbamoylamino) pyridine-2-carboxamide (compound 64.1);

n-tert-butyl-4- (2-phenylethylcarbamoylamino) pyridine-2-carboxamide (compound 64.2);

n-tert-butyl-4- [ [ (1R) -1-phenylethyl ] carbamoylamino ] pyridine-2-carboxamide (compound 64.3);

n-tert-butyl-4- [ [ (1S) -1-phenylethyl ] carbamoylamino ] pyridine-2-carboxamide (compound 64.4);

n-tert-butyl-4- [ (2-chlorophenyl) methylcarbamoylamino ] pyridine-2-carboxamide (compound 64.5);

n-tert-butyl-4- (1H-indol-3-ylcarbamoylamino) pyridine-2-carboxamide (compound 64.6);

n-tert-butyl-4- [ (3-chlorophenyl) methylcarbamoylamino ] pyridine-2-carboxamide (compound 64.7);

N-tert-butyl-4- [ (4-chlorophenyl) methylcarbamoylamino ] pyridine-2-carboxamide (Compound 64.8);

n-tert-butyl-4- [ (2-hydroxyphenyl) carbamoylamino ] pyridine-2-carboxamide (compound 65);

n-tert-butyl-4- [ (2-methoxyphenyl) methylcarbamoylamino ] pyridine-2-carboxamide (compound 65.1);

n-tert-butyl-4- [ (2-hydroxyphenyl) methylcarbamoylamino ] pyridine-2-carboxamide (Compound 65.2);

n-tert-butyl-4- [ (3-hydroxyphenyl) methylcarbamoylamino ] pyridine-2-carboxamide (compound 65.3);

n-tert-butyl-4- [ (4-hydroxyphenyl) methylcarbamoylamino ] pyridine-2-carboxamide (compound 65.4);

n-tert-butyl-4- [ [2- [ 2-hydroxy-5- (1-hydroxyethyl) phenyl ] acetyl ] amino ] pyridine-2-carboxamide (compound 66);

n-tert-butyl-4- [ [2- [ 2-hydroxy-5- [1- (2,2, 2-trifluoroethylamino) ethyl ] phenyl ] acetyl ] amino ] pyridine-2-carboxamide (compound 67);

n-tert-butyl-4- [ [2- [3- (cyanomethyl) phenyl ] acetyl ] amino ] pyridine-2-carboxamide (compound 68);

n-tert-butyl-4- [ [2- [3- (methoxymethyl) phenyl ] acetyl ] amino ] pyridine-2-carboxamide (compound 69);

n-tert-butyl-4- [ [2- [ 2-hydroxy-5- (morpholinomethyl) phenyl ] acetyl ] amino ] pyridine-2-carboxamide (compound 70);

3- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (3-cyanotetrahydrofuran-3-yl) benzamide (compound 71);

3- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (1-methylcyclohexyl) benzamide (compound 71.1);

4- [ [2- (5-fluoro-2-hydroxy-phenyl) acetyl ] amino ] -N- [3- (hydroxymethyl) tetrahydrofuran-3-yl ] pyridine-2-carboxamide (compound 72);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [1- (hydroxymethyl) -2-methoxy-1-methyl-ethyl ] pyridine-2-carboxamide (compound 73);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (1, 1-dimethylbut-2-ynyl) pyridine-2-carboxamide (compound 73.1);

3- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (1, 1-dimethylprop-2-ynyl) benzamide (compound 74);

3- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [3- (hydroxymethyl) tetrahydrofuran-3-yl ] benzamide (compound 74.1);

n-tert-butyl-4- [ [2- [ 2-hydroxy-5- (3-hydroxypropyl) phenyl ] acetyl ] amino ] pyridine-2-carboxamide (compound 75);

4- [ [2- (5-chloro-4-fluoro-2-hydroxy-phenyl) acetyl ] amino ] -N- (1-methylcyclobutyl) pyridine-2-carboxamide (compound 76);

4- [ [2- (2, 5-difluorophenyl) acetyl ] amino ] -N- (1, 1-dimethylprop-2-ynyl) pyridine-2-carboxamide (compound 77);

4- [ [2- (2, 5-difluorophenyl) acetyl ] amino ] -N- (4-fluoro-1-bicyclo [2.1.1] hexyl) pyridine-2-carboxamide (compound 77.1);

4- [ [2- (4-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (1, 1-dimethylprop-2-ynyl) pyridine-2-carboxamide (compound 78);

n- (1, 1-dimethylprop-2-ynyl) -4- [ [2- [ 2-hydroxy-4- (trifluoromethyl) phenyl ] acetyl ] amino ] pyridine-2-carboxamide (compound 78.1);

n- (1, 1-dimethylprop-2-ynyl) -4- [ [2- [ 2-hydroxy-5- (trifluoromethyl) phenyl ] acetyl ] amino ] pyridine-2-carboxamide (compound 78.2);

4- [ (2-chroman-4-ylacetyl) amino ] -N- (1, 1-dimethylprop-2-ynyl) pyridine-2-carboxamide (compound 79);

n- (1, 1-dimethylprop-2-ynyl) -4- [ [2- (1-isopropyl-3, 5-dimethyl-pyrazol-4-yl) acetyl ] amino ] pyridine-2-carboxamide (compound 79.1);

n- (1, 1-dimethylprop-2-ynyl) -4- [ [2- (1H-indazol-4-yl) acetyl ] amino ] pyridine-2-carboxamide (compound 79.2);

n- (1, 1-dimethylprop-2-ynyl) -4- [ [2- (1H-indol-7-yl) acetyl ] amino ] pyridine-2-carboxamide (compound 79.3);

3- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (4-cyanotetrahydropyran-4-yl) benzamide (compound 80);

n- (1-cyano-1-methyl-ethyl) -4- [ [2- (5-fluoro-2-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 81);

N- (1-cyano-2-hydroxy-1-methyl-ethyl) -4- [ [2- (5-fluoro-2-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 81.1);

4- [ [2- (5-fluoro-2-hydroxy-phenyl) acetyl ] amino ] -N-isopropyl-pyridine-2-carboxamide (compound 81.2);

n- (1, 1-dimethylprop-2-ynyl) -4- [ [2- (5-fluoro-2-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 81.3);

n- (4-fluoro-1-bicyclo [2.1.1] hexyl) -4- [ [2- (5-fluoro-2-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 81.4);

4- [ [2- (5-fluoro-2-hydroxy-phenyl) acetyl ] amino ] -N- [1- (hydroxymethyl) cyclobutyl ] pyridine-2-carboxamide (compound 81.5);

n-tert-butyl-6- [ [2- (5-chloro-2-methoxy-phenyl) acetyl ] amino ] pyrimidine-4-carboxamide (compound 82);

n- (1-cyano-1-methyl-ethyl) -4- (thiophene-3-carbonylamino) pyridine-2-carboxamide (compound 83);

n- (1-cyano-1-methyl-ethyl) -4- [ (2-cyclohexylacetyl) amino ] pyridine-2-carboxamide (compound 83.1);

n- (1-cyano-1-methyl-ethyl) -4- (cyclohexanecarbonylamino) pyridine-2-carboxamide (compound 83.2);

n- (1-cyano-1-methyl-ethyl) -4- [ (3, 3-difluorocyclopentanecarbonyl) amino ] pyridine-2-carboxamide (compound 83.3);

N- (1-cyano-1-methyl-ethyl) -4- [ (1-methylcyclopentanecarbonyl) amino ] pyridine-2-carboxamide (compound 83.4);

n- (1-cyano-1-methyl-ethyl) -4- (3-cyclohexylpropionylamino) pyridine-2-carboxamide (compound 83.5);

4- (2- { bicyclo [2.2.1] hept-2-yl } acetylamino) -N- (1-cyano-1-methylethyl) pyridine-2-carboxamide (compound 83.6);

n- (1-cyano-1-methyl-ethyl) -4- [ [2- (1-methylcyclohexyl) acetyl ] amino ] pyridine-2-carboxamide (compound 83.7);

n- [2- [ (1-cyano-1-methyl-ethyl) carbamoyl ] -4-pyridyl ] -2-cyclopropyl-pyrimidine-5-carboxamide (compound 83.8);

n- [2- [ (1-cyano-1-methyl-ethyl) carbamoyl ] -4-pyridinyl ] -3-isobutyl-isoxazole-5-carboxamide (compound 83.9);

n- (1-cyano-1-methyl-ethyl) -4- [ [2- (4, 4-difluorocyclohexyl) acetyl ] amino ] pyridine-2-carboxamide (compound 83.10);

4- [ (1-benzylcyclopropanecarbonyl) amino ] -N- (1-cyano-1-methyl-ethyl) pyridine-2-carboxamide (compound 83.11);

n- (1-cyano-1-methyl-ethyl) -4- [3- (2-methoxy-4-pyridyl) propionylamino ] pyridine-2-carboxamide (compound 83.13); 4- [ (5-tert-butyl-2-methyl-pyrazole-3-carbonyl) amino ] -N- (1-cyano-1-methyl-ethyl) pyridine-2-carboxamide (compound 83.14);

N- (1-cyano-1-methyl-ethyl) -4- [ (2-pyrazol-1-ylbenzoyl) amino ] pyridine-2-carboxamide (compound 83.15);

n- [2- [ (1-cyano-1-methyl-ethyl) carbamoyl ] -4-pyridyl ] -6- (trifluoromethyl) pyridine-2-carboxamide (compound 83.16);

n- [2- [ (1-cyano-1-methyl-ethyl) carbamoyl ] -4-pyridyl ] -3-oxo-4H-1, 4-benzoxazine-7-carboxamide (compound 83.17);

n- [2- [ (1-cyano-1-methyl-ethyl) carbamoyl ] -4-pyridyl ] -1-ethyl-indole-2-carboxamide (compound 83.18);

n- (1-cyano-1-methyl-ethyl) -4- [ [2- (2,2, 2-trifluoroethyl) pyrazole-3-carbonyl ] amino ] pyridine-2-carboxamide (compound 83.19);

n- [2- [ (1-cyano-1-methyl-ethyl) carbamoyl ] -4-pyridinyl ] -3-phenyl-isoxazole-4-carboxamide (compound 83.20);

4- [ (1-benzylpyrazole-4-carbonyl) amino ] -N- (1-cyano-1-methyl-ethyl) pyridine-2-carboxamide (compound 83.21);

n- (1-cyano-1-methyl-ethyl) -4- [ (2-methyl-5-phenyl-pyrazole-3-carbonyl) amino ] pyridine-2-carboxamide (compound 83.22);

n- (1-cyano-1-methyl-ethyl) -4- [ [2- (3-methyl-1, 2, 4-oxadiazol-5-yl) benzoyl ] amino ] pyridine-2-carboxamide (compound 83.23);

n- (1-cyano-1-methyl-ethyl) -4- [ (3-methyl-1-phenyl-pyrazole-4-carbonyl) amino ] pyridine-2-carboxamide (compound 83.24);

N- [2- [ (1-cyano-1-methyl-ethyl) carbamoyl ] -4-pyridyl ] -2-phenoxy-pyridine-3-carboxamide (compound 83.25);

n- (1-cyano-1-methyl-ethyl) -4- [ [2, 5-dimethyl-1- (2-thienylmethyl) pyrrole-3-carbonyl ] amino ] pyridine-2-carboxamide (compound 83.26);

n- [2- [ (1-cyano-1-methyl-ethyl) carbamoyl ] -4-pyridinyl ] -5- (2-methoxyphenyl) isoxazole-3-carboxamide (compound 83.27);

n- [2- [ (1-cyano-1-methyl-ethyl) carbamoyl ] -4-pyridyl ] -4-methyl-2-phenyl-thiazole-5-carboxamide (compound 83.28);

4- [ (4-Acetylaminobenzoyl) amino ] -N- (1-cyano-1-methyl-ethyl) pyridine-2-carboxamide (Compound 83.29);

n- [2- [ (1-cyano-1-methyl-ethyl) carbamoyl ] -4-pyridyl ] -1, 3-benzothiazole-7-carboxamide (compound 83.30);

n- (1-cyano-1-methyl-ethyl) -4- [3- (4-fluorophenyl) butyrylamino ] pyridine-2-carboxamide (compound 83.31);

n- [2- [ (1-cyano-1-methyl-ethyl) carbamoyl ] -4-pyridyl ] -1-methyl-2-oxo-quinoline-3-carboxamide (compound 83.32);

n-tert-butyl-3- [ [2- (2-hydroxycyclohexyl) acetyl ] amino ] benzamide (compound 84);

n-tert-butyl-6- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] pyrimidine-4-carboxamide (compound 85);

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- [ 1-cyano-2-methoxy-1- (methoxymethyl) ethyl ] pyridine-2-carboxamide (compound 86);

4- [ [2- (3-amino-4-tert-butyl-phenyl) acetyl ] amino ] -N-tert-butyl-pyridine-2-carboxamide (compound 87);

4- [ [2- (2-amino-4-tert-butyl-phenyl) acetyl ] amino ] -N-tert-butyl-pyridine-2-carboxamide (compound 88);

n-tert-butyl-4- [ [2- (4-tert-butyl-3-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 89);

n-tert-butyl-4- [ [2- (4-tert-butyl-2-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 90);

n-tert-butyl-4- [ [2- (4-tert-butyl-2-fluoro-5-hydroxy-phenyl) acetyl ] amino ] pyridine-2-carboxamide (compound 91);

4- [ [2- (4-chloro-3-hydroxy-phenyl) acetyl ] amino ] -N- (4-cyanotetrahydropyran-4-yl) pyridine-2-carboxamide (compound 92);

4- [ [2- (4-chloro-3-hydroxy-phenyl) acetyl ] amino ] -N- (1-cyano-1-methyl-ethyl) pyridine-2-carboxamide (compound 92.1);

4- [ [2- (4-chloro-3-hydroxy-phenyl) acetyl ] amino ] -N- (1, 1-dimethylprop-2-ynyl) pyridine-2-carboxamide (compound 92.2);

4- [ [2- (4-chloro-3-hydroxy-phenyl) acetyl ] amino ] -N- [ (1s,2s) -2-hydroxycyclopentyl ] pyridine-2-carboxamide (compound 92.3);

4- [ [2- (4-tert-butyl-3-hydroxy-phenyl) acetyl ] amino ] -N- [3- (hydroxymethyl) tetrahydrofuran-3-yl ] pyridine-2-carboxamide (compound 93);

4- [ [2- (4-tert-butyl-3-hydroxy-phenyl) acetyl ] amino ] -N- [ (2S) -2-hydroxycyclohexyl ] pyridine-2-carboxamide (compound 93.1);

4- [ [2- (4-tert-butyl-3-hydroxy-phenyl) acetyl ] amino ] -N- [ (2S) -2-hydroxycyclopentyl ] pyridine-2-carboxamide (compound 93.2);

4- [ [2- (4-tert-butyl-3-hydroxy-phenyl) acetyl ] amino ] -N- (4-cyanotetrahydropyran-4-yl) pyridine-2-carboxamide (compound 93.3);

4- [ [2- (4-tert-butyl-3-hydroxy-phenyl) acetyl ] amino ] -N- (1-cyano-1-methyl-ethyl) pyridine-2-carboxamide (compound 93.4);

4- [ [2- (4-tert-butyl-3-hydroxy-phenyl) acetyl ] amino ] -N- (1, 1-dimethylprop-2-ynyl) pyridine-2-carboxamide (compound 93.5); and

4- [ [2- (5-chloro-2-hydroxy-phenyl) acetyl ] amino ] -N- (1-methyl-1-phenyl-ethyl) pyridine-2-carboxamide (compound 94);

and salts and solvates of any of the above.

23. A compound for use, use or method according to any one of claims 1 to 22 wherein the compound of general formula (I), (Iz), (Iy), (Ix), (Ia), (Ib), (Ic), (Id) or (Ie) is used in combination with a further active agent for the treatment or prophylaxis of a respiratory disorder.

24. A compound of general formula (I), (Iz), (Iy), (Ix), (Ia), (Ib), (Ic), (Id) or (Ie) as defined in any one of claims 1 or 10 to 22, with the proviso that:

when X is present¹Is N and X²When CH is present, Z is-C (O) -and Y is a bond, R⁴A 5-to 10-membered heteroaryl or heterocyclic ring not linked to Y via a nitrogen atom; and is

When X is present¹And X²When all are CH, R⁴Is phenyl having an OH in the 2-or 3-position, and optionally having one or more further substituents as defined in claim 1; and is

When X is present¹Is CH and X²When N is:

when Z is-C (O) -Y is not a bond; and is

When Z is-C (O) NH-and Y is a bond, R⁴Is not a 12-membered heteroaryl ring system; and is

When X is present¹And X²Are all N, and when R¹And R²Is H and R¹And R²When the other is H or methyl, R³Is not substituted or unsubstituted phenyl.

25. A compound according to claim 24, selected from: