阅读说明：本技术 作为lsd1抑制剂的杂螺环类化合物及其应用 (Heterospirocyclic compounds as LSD1 inhibitors and application thereof ) 是由 吴凌云 汪秋燕 黎健 陈曙辉 于 2019-09-12 设计创作，主要内容包括：涉及一类可作为赖氨酸特异性去甲基化酶1(LSD1)抑制剂的杂螺环类化合物,还涉及其在制备治疗与LSD1相关疾病的药物中的应用。具体涉及一种如式(Ⅰ)所示化合物、其异构体及其药学上可接受的盐。(Relates to a heterocyclic spiro compound which can be used as a lysine specific demethylase 1(LSD1) inhibitor, and also relates to application thereof in preparing medicaments for treating diseases related to LSD 1. In particular to a compound shown as a formula (I), an isomer and pharmaceutically acceptable salt thereof.)

A compound of formula (I), an isomer thereof or a pharmaceutically acceptable salt thereof,

wherein the content of the first and second substances,

L ₁is selected from- (CH)₂)g-、-C(＝O)-、-S(＝O) ₂-, -C (═ O) -O-, and-C (═ O) -NH-;

R ₁is selected from NH₂、CN、COOH、-S(＝O) ₂-NH ₂、C _1-6Alkyl, -C (═ O) -C_1-4Alkyl-phenyl and-C_1-4Alkyl-4-7 membered heterocycloalkyl,

wherein said C_1-6Alkyl, -C (═ O) -C_1-4Alkyl-phenyl and-C_1-4Alkyl-4-7 membered heterocycloalkyl optionally substituted with 1,2 or 3R_aSubstitution;

m is 0, 1 or 2;

n is 0, 1 or 2, and m and n cannot be 0 at the same time;

r is 0 or 1;

q is 0 or 1;

g is 0, 1,2, 3 or 4;

R _aselected from F, Cl, Br, I, OH, NH₂、CN、COOH、C _1-3Alkylamino and-NH-C (═ O) -C_1-3Alkyl radical, wherein said C_1-3Alkylamino and-NH-C (═ O) -C_1-3Alkyl is optionally substituted with 1,2 or 3R;

r is selected from F, Cl, Br, I, OH and NH₂And C_1-3An alkyl group;

said 4-7 membered heterocycloalkyl contains 1,2, 3 or 4 heteroatoms or groups of heteroatoms independently selected from-NH-, -O-, -S-and N;

with "-" carbon atoms as chiral carbon atoms, in the form of (R) or (S) single enantiomers or enriched in one enantiomer;

the carbon atom with "#" is a chiral carbon atom and exists in the form of a single enantiomer (R) or (S) or in a form enriched in one enantiomer.

A compound, isomer, or pharmaceutically acceptable salt thereof according to claim 1, wherein R is selected from F, Cl, Br, I, OH, NH₂、CH ₃and-CH₂CH ₃。

The compound, an isomer thereof, or a pharmaceutically acceptable salt thereof according to claim 1 or 2, wherein R_aSelected from F, Cl, Br, I, OH, NH₂、CN、COOH、 Wherein said Optionally substituted with 1,2 or 3R.

A compound, isomer, or pharmaceutically acceptable salt thereof according to claim 3, wherein R_aSelected from F, Cl, Br, I, OH, NH₂、CN、COOH、

A compound, isomer, or pharmaceutically acceptable salt thereof according to claim 1, wherein R₁Is selected from NH₂、CN、COOH、 -S(＝O) ₂-NH ₂、C _1-4Alkyl, -C (═ O) -C_1-3Alkyl-phenyl and-C_1-3Alkyl-5-6 heterocycloalkyl wherein said C_1-4Alkyl, -C (═ O) -C_1-3Alkyl-phenyl and-C_1-3Alkyl-5-6 heterocycloalkyl optionally substituted with 1,2 or 3R_aAnd (4) substitution.

A compound, isomer, or pharmaceutically acceptable salt thereof according to claim 5, wherein R₁Is selected from NH₂、CN、COOH、-S(＝O) ₂-NH ₂、-CH ₃、-CH ₂-CH ₃、 Wherein said CH₃、-CH ₂-CH ₃、 Optionally substituted by 1,2 or 3R_aAnd (4) substitution.

A compound, isomer, or pharmaceutically acceptable salt thereof according to claim 6, wherein R₁Is selected from NH₂、CN、COOH、 -CH ₃、-CH ₂-CH ₃、

A compound, isomer, or pharmaceutically acceptable salt thereof according to claim 1, wherein L₁Selected from single bonds, -CH₂-、-(CH ₂) ₂-、 -C (═ O) -, and-S (═ O)₂-。

The compound according to any one of claims 1 to 7, an isomer thereof or a pharmaceutically acceptable salt thereof, which is selected from the group consisting of

Wherein the content of the first and second substances,

g is as defined in claim 1;

R ₁as defined in any one of claims 1 to 6.

A compound of the formula, an isomer thereof or a pharmaceutically acceptable salt thereof,

the compound according to claim 10, an isomer thereof, or a pharmaceutically acceptable salt thereof,

the compound, an isomer thereof, or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 11, wherein the pharmaceutically acceptable salt is selected from hydrochloride salts.

Use of a compound according to any one of claims 1-12, an isomer thereof, or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for the treatment of a disorder associated with LSD 1.