Chemical compound as thyroid hormone beta receptor agonist and use thereof
AssigneeSunshine Lake Pharma Co., Ltd.
InventorsZheng Gu, Jianhao Li, Xinshan Deng, Zheng Li, Daoqian Chen, Jianchao Deng, Aizhen Lv, Jianyu Liu
Life of this patent
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Abstract
Provided is a chemical compound as a thyroid hormone Beta receptor agonist and a use thereof, further comprising a pharmaceutical composition containing the chemical compound. The chemical compound or pharmaceutical composition can be used in the preparation of drugs for preventing, treating or mitigation of diseases mediated by agonistic thyroid hormone β receptor, particularly for the preparation of drugs for treating non-alcoholic fatty liver diseases.
Claims9
A compound having Formula (I) or a stereoisomer, a tautomer, an N-oxide, a solvate, or a pharmaceutically acceptable salt thereof,
- wherein,
- Y is —O—, —S—, —NRc—, —CRaRb—, —S(═O)2—, —S(═O)— or —C(═O)—;
- L is absent, —O—, —S—, —NRc—, —CRdRe—, —S(═O)2—, —S(═O)— or —C(═O)—;
- each of Ra, Rb, Rc, Rd and Re is independently H, deuterium, F, Cl, Br, I, —CN, —NO2, —COOH, —OH, —NH2, —SH, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl or C1-6 haloalkoxy;
- each of R3a, R3b, R3c, and R3d is independently H, deuterium, F, Cl, Br, I, —CN, —NO2, —COOH, —OH, —NH2, —SH, C1-6 alkyl, C1-6 alkoxy, C1-6 alkylthio, C1-6 alkylamino, C1-6 haloalkyl, C1-6 haloalkoxy, hydroxy C1-6 alkyl, amino C1-6 alkyl or cyano C1-6 alkyl;
- M is —C(═O)—, —C(═S)—, —S(═O)2— or —S(═O)—;
- E1 is N or CH;
- E2 is CR2;
- E3 is N or CR3;
- each of R2 and R3 is independently H or deuterium;
- R1 is C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, —C(═O)—C1-6 alkoxy, —C(═O)—C1-6 alkylamino, —C(═O)—C1-6 alkyl, —S(═O)2—C1-6 alkyl, —S(═O)2—C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, 5-8 membered heterocyclyl, C6-10 aryl or 5-8 membered heteroaryl, wherein each of the C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, —C(═O)—C1-6 alkoxy, —C(═O)—C1-6 alkylamino, —C(═O)—C1-6 alkyl, —S(═O)2—C1-6 alkyl, —S(═O)2—C1-6 alkylamino, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, 5-8 membered heterocyclyl, C6-10 aryl and 5-8 membered heteroaryl is independently unsubstituted or substituted with 1, 2 or 3 substituents selected from Deuterium, F, Cl, Br, I, —CN, —NO2, —COOH, —C(═O)NH2, —S(═O)2NH2, —SH, —OH, —NH2, ═O, —C(═O)—C1-6 alkyl, —C(═O)—C1-6 alkoxy, C1-6 alkyl, C1-6 alkoxy, C1-6 haloalkyl or C1-6 haloalkoxy;
- W is
- R4 is H, deuterium, F, Cl, Br, I, —CN, —NO2, —COOH, —OH, —NH2, —SH, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, —C(═O)—C1-6 alkoxy, —C(═O)—C1-6 alkyl, —C(═O)—C1-6 alkylamino, —C(═O)NH2, —S(═O)2—C1-6 alkyl, —S(═O)2—C1-6 alkylamino, C1-6 alkylamino, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, hydroxy C1-6 alkyl, amino C1-6 alkyl, carboxy C1-6 alkyl or cyano C1-6 alkyl, wherein each of the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, —C(═O)—C1-6 alkoxy, —C(═O)—C1-6 alkyl, —C(═O)—C1-6 alkylamino, —C(═O)NH2, —S(═O)2—C1-6 alkyl, —S(═O)2—C1-6 alkylamino, C1-6 alkylamino, C1-6 alkoxy, C1-6 haloalkyl, C1-6 haloalkoxy, hydroxy C1-6 alkyl, amino C1-6 alkyl, carboxy C1-6 alkyl and cyano C1-6 alkyl is independently unsubstituted or substituted with 1, 2 or 3 substituents selected from deuterium, F, Cl, Br, I, —CN, —NO2, —COOH, —OH, —NH2, —SH, C1-6 alkyl, C2-6 alkenyl or C2-6 alkynyl;
- R5 is H, deuterium, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, 5-6 membered heterocyclyl, C6-10 aryl or 5-6 membered heteroaryl.
A compound having one of the following structures:
- or a stereoisomer, a tautomer, an N-oxide, a solvate, or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.