Fused tricyclic derivative and pharmaceutical application thereof

Patent metadata

Field	Value
Publication number	US-12590082-B2
Application number	US-202118027049-A
Country	US
Kind code	B2
Filing date	Sep 28, 2021
Priority date	Sep 28, 2020
Publication date	Mar 31, 2026
Grant date	Mar 31, 2026

Abstract

Disclosed are a fused tricyclic derivative and a pharmaceutical application thereof. Specifically disclosed are a compound represented by formula (III) and a pharmaceutically acceptable salt thereof.

First claim

The invention claimed is:

1 . A compound of formula (III) or a pharmaceutically acceptable salt thereof,

wherein,
R 1 is selected from the group consisting of H, halogen, C 1-4 alkyl and phenyl;
R 2 is each independently selected from the group consisting of H, halogen and C 1-4 alkyl;
or two R 2 , together with the thiophene ring to which they are connected, form benzothiophene;
n is selected from the group consisting of 1 and 2;
T 1 is selected from the group consisting of a single bond, —NH— and —N(CH 3 )—;
L 1 is selected from the group consisting of a single bond and —CH 2 —;
the structural unit

is selected from the group consisting of

ring A is selected from the group consisting of the following groups optionally substituted with 1 or 2 R b : C 4-6 cycloalkenyl, 4- to 6-membered heterocycloalkenyl, 5- to 6-membered heteroaryl,

and phenyl;
R b is each independently selected from the group consisting of —F, —Cl, —Br, —I, —CH 3 and —CH 2 CH 3 ;
ring B is selected from the group consisting of cyclopentyl, cyclohexyl and 6- to 10-membered heterocycloalkyl, wherein the 6- to 10-membered heterocycloalkyl is optionally substituted with 1 R a ;
R a is selected from the group consisting of —F, —Cl, methyl, —OH and —CN;
wherein “hetero” of the “6- to 10-membered heterocycloalkyl” comprises 1, 2 or 3 heteroatoms or heteroatom groups independently selected from the group consisting of O, S, NH and N, wherein the nitrogen atom is optionally quaternized with methyl halide.

2 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein R 1 is selected from the group consisting of H, —Cl, —Br, methyl, tert-butyl and phenyl.

3 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein R 2 is each independently selected from the group consisting of H, —Cl, —Br, methyl and tert-butyl.

4 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein T 1 is selected from the group consisting of a single bond and —N(CH 3 )—.

5 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein ring B is selected from the group consisting of cyclohexyl and 6- to 10-membered heterocycloalkyl, wherein the 6- to 10-membered heterocycloalkyl is optionally substituted with 1 R a .

6 . The compound or the pharmaceutically acceptable salt thereof according to claim 5 , wherein ring B is selected from the group consisting of cyclohexyl and the following groups optionally substituted with 1 R a : piperidinyl, piperazinyl, morpholinyl, dioxanyl, dithianyl, tetrahydrooxazinyl, tetrahydrothiazinyl, hexahydropyridazinyl, homopiperazinyl, homopiperidinyl, dioxepanyl,

7 . The compound or the pharmaceutically acceptable salt thereof according to claim 6 , wherein ring B is selected from the group consisting of cyclohexyl and the following groups optionally substituted with 1 R a : piperidinyl, piperazinyl,

8 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein the structural unit

is selected from the group consisting of

9 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein the structural unit

is selected from the group consisting of

10 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein the structural unit

is selected from the group consisting of

11 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein R a is selected from the group consisting of —F, —CH 3 , —OH and —CN.

12 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein R b is each independently selected from the group consisting of —F, —Cl, —Br, —I and —CH 3 .

13 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein ring A is selected from the group consisting of the following groups optionally substituted with 1 or 2 R b :

pyrrolyl, thienyl, furanyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, triazolyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl,

and phenyl.

14 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein ring A is selected from the group consisting of the following groups optionally substituted with 1 or 2 R b :

pyrazolyl and phenyl.

15 . The compound or the pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound is selected from the group consisting of structures of (III-1), (III-2), (III-3), (IV-1), (IV-2) and (V-1),

16 . Compounds as shown below or pharmaceutically acceptable salts thereof,

17 . The compounds or the pharmaceutically acceptable salts thereof according to claim 16 , wherein the compounds are selected from the group consisting of:

18 . A pharmaceutical composition c

Assignees

• Chia Tai Tianqing Pharmaceutical Group Co Ltd

Inventors

• Zhang Peng
• Luo Yunfu
• Gao Feng
• Chen Shuhui

Classifications

• C07D491/107

  with only one oxygen atom as ring hetero atom in the oxygen-containing ring · CPC title

• C07D491/056

  with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring · CPC title

• C07D491/048

  the oxygen-containing ring being five-membered · CPC title

• C07D487/04

  Ortho-condensed systems · CPC title

• C07D413/14

  containing three or more hetero rings · CPC title