Fused pyridine ring derivative, preparation method therefor, and pharmaceutical use thereof

Patent metadata

Field	Value
Publication number	US-12428396-B2
Application number	US-202017756545-A
Country	US
Kind code	B2
Filing date	Nov 27, 2020
Priority date	Nov 29, 2019
Publication date	Sep 30, 2025
Grant date	Sep 30, 2025

Abstract

A fused pyridine ring derivative represented by general formula (I), a preparation method therefor, a pharmaceutical composition containing the derivative, and a use thereof as a therapeutic agent, particularly, in preparation of drugs for preventing and/or treating HIV infection.

First claim

The invention claimed is:

1. A compound of general formula (I) or an atropisomer, tautomer, mesomer, racemate, enantiomer, diastereomer thereof or a mixture thereof, or a pharmaceutically acceptable salt thereof,

wherein,
ring A is selected from the group consisting of cycloalkyl and aryl;
L 1 is alkylene;
L 2 is absent or selected from the group consisting of —CH 2 —, —O—, —S— and —NR 6 —;
R 1 is selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the cycloalkyl, heterocyclyl, aryl and heteroaryl are each independently optionally substituted with one or more substituents selected from the group consisting of oxo, halogen, alkyl, haloalkyl, cyano, amino, nitro, hydroxy, hydroxyalkyl and cycloalkyl;
R 1a and R 1b are identical or different and are each independently selected from the group consisting of hydrogen, halogen, alkyl and haloalkyl;
R 2 is selected from the group consisting of cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the cycloalkyl, heterocyclyl, aryl and heteroaryl are each independently optionally substituted with one or more substituents selected from the group consisting of oxo, halogen, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, cyano, amino, nitro, hydroxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —OR 6 , —OC(O)R 6 , —OC(O)NR 7 R 8 , —NHS(O) r R 6 , —NHS(O) 2 OR 6 , —NHS(O) 2 NR 7 R 8 , —C(O)R 6 , —C(O)OR 6 , —C(O)NR 7 R 8 , —S(O) r R 6 , —S(O) r NR 7 R 8 , —NR 7 R 8 , —NHC(O)R 6 , —NHC(O)OR 6 , —NHC(O)NR 7 R 8 and —NHC(O)NHOR 6 ;
R 3 is C 2-12 alkynyl, the C 2-12 alkynyl being optionally substituted with one or more —S(O) 2 R 9 ; R 9 is C 1-6 alkyl or C 3-6 cycloalkyl;
R 4 is identical or different and is each independently selected from the group consisting of hydrogen, halogen, alkyl, alkoxy, haloalkyl, cyano, amino, nitro, hydroxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
R 5 is identical or different and is each independently selected from the group consisting of hydrogen, halogen, alkyl, alkoxy, haloalkyl, cyano, amino, nitro, hydroxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl;
R 6 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is each independently optionally substituted with one or more substituents selected from the group consisting of alkyl, halogen, hydroxy, alkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl;
R 7 and R 8 are identical or different and are each independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —C(O)R 6 and —S(O) r R 6 , wherein the alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl are each independently optionally substituted with one or more substituents selected from the group consisting of alkyl, halogen, hydroxy, alkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl;
m is 0, 1, 2, 3, 4, 5 or 6;
n is 0, 1, 2, 3, 4 or 5; and
r is 0, 1 or 2.

2. The compound of general formula (I) or the atropisomer, tautomer, mesomer, racemate, enantiomer, diastereomer thereof or the mixture thereof, or the pharmaceutically acceptable salt thereof according to claim 1 , wherein L 1 is methylene; and L 2 is absent.

3. The compound of general formula (I) or the atropisomer, tautomer, mesomer, racemate, enantiomer, diastereomer thereof or the mixture thereof, or the pharmaceutically acceptable salt thereof according to claim 1 , wherein R 1 is

R 1c , R 1d and R 1e are identical or different and are each independently selected from the group consisting of hydrogen, halogen, alkyl, haloalkyl, cyano, amino, nitro, hydroxy, hydroxyalkyl and cycloalkyl.

4. The compound of general formula (I) or the atropisomer, tautomer, mesomer, racemate, enantiomer, diastereomer thereof or the mixture thereof, or the pharmaceutically acceptable salt thereof according to claim 1 , wherein R 2 is

R 2a , R 2b and R 2c are identical or different and are each independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, cyano, amino, nitro, hydroxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —OR 6 , —OC(O) R 6 , —OC(O)NR 7 R 8 , —NHS(O) r R 6 , —NHS(O) 2 OR 6 , —NHS(O) 2 NR 7 R 8 , —C(O)R 6 , —C(O)OR 6 , —C(O)NR 7 R 8 , —S(O) r R 6 , —S(O) r NR 7 R 8 , —NR 7 R 8 , —NHC(O)R 6 , —NHC(O)OR 6 , —NHC(O)NR 7 R 8 and —NHC(O)NHOR 6 ; R 6 -R 8 and r are as defined in claim 1 .

5. The compound of general formula (I) or the atropisomer, tautomer, mesomer, racemate, enantiomer, diastereomer thereof or the mixture thereof, or the pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound of general formula (I) or the atropisomer, tautomer, mesomer, racemate, enantiomer, diastereomer thereof or the mixture thereof, or the pharmaceutically acceptable salt thereof is a compound of general formula (III) or general formula (III-1) or an atropisomer, tautomer, mesomer, racemate, enantiomer, diastereomer thereof or a mixture thereof, or a pharmaceutically acceptable salt thereof,

wherein,
R 1c , R 1d and R 1e are identical or different and are each independently selected from the group consisting of hydrogen, halogen, alkyl, haloalkyl, cyano, amino, nitro, hydroxy, hydroxyalkyl and cycloalkyl;
R 2a , R 2b and R 2c are identical or different and are each independently selected from the group consisting of hydrogen, halogen, alkyl, alkenyl, alkynyl, alkoxy, haloalkyl, cyano, amino, nitro, hydroxy, hydroxyalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, —OR 6 , —OC(O)R 6 , —OC(O)NR 7 R 8 , —NHS(O) r R 6 , —NHS(O) 2 OR 6 , —NHS(O) 2 NR 7 R 8 , —C(O)R 6 , —C(O)OR 6 , —C(O)NR 7 R 8 , —S(O) r R 6 , —S(O) r NR 7 R 8 , —NR 7 R 8 , —NHC(O)R 6 , —NHC(O)OR 6 , —NHC(O)NR 7 R 8 and —NHC(O)NHOR 6 ; and
ring A, R 3 -R 8 , m, n and r are as defined in claim 1 .

6. The compound of general formula (I) or the atropisomer, tautomer, mesomer, racemate, enantiomer, diastereomer thereof or the mixture thereof, or the pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound of general formula (I) or the atropisomer, tautomer, mesomer, racemate, enantiomer, diastereomer thereof or the mixture thereof, or the pharmaceutically acceptable salt thereof is a compound of general formula (III-1a) or an atropisomer, tautomer, mesomer, racemate, enantiomer, diastereomer thereof or a mixture thereof, or a pharmaceutically acceptable salt thereof,

wherein, ring A, R 1c , R 1d , R 1e , R 2a , R 2b , R 2c , R 3 , R 4 , R 5 , n and m are as defined in claim 5 .

7. The compound of general formula (I) or the atropisomer, tautomer, mesomer, racemate, enantiomer, diastereomer thereof or the mixture thereof, or the pharmaceutically acceptable salt thereof according to claim 1 , wherein ring A is selected from the group consisting of C 3-6 cycloalkyl and phenyl.

8. The compound of general formula (I) or the atropisomer, tautomer, mesomer, racemate, enantiomer, diastereomer thereof or

Assignees

• Jiangsu Hengrui Medicine Co
• Shanghai hengrui pharmaceutical co ltd

Inventors

• Zhang Xiaomin
• Hu Weimin
• He Feng
• Ye Chaobaihui

Classifications

• A61P31/18 Primary

  for HIV · CPC title

• A61K31/4725

  containing further heterocyclic rings · CPC title

• A61K31/435

  having six-membered rings with one nitrogen as the only ring hetero atom · CPC title

• C07D401/04 Primary

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D401/14 Primary

  containing three or more hetero rings · CPC title