Aromatic ring or heteroaromatic ring derivatives, preparation method therefor and use thereof

Patent metadata

Field	Value
Publication number	US-12559449-B2
Application number	US-202017610162-A
Country	US
Kind code	B2
Filing date	Apr 1, 2020
Priority date	May 10, 2019
Publication date	Feb 24, 2026
Grant date	Feb 24, 2026

Abstract

The present invention relates to aromatic ring or heteroaromatic ring derivatives, a preparation method therefor and applications thereof in medicine. Specifically, the present invention relates to aromatic ring or heteroaromatic ring derivatives represented by general formula (I), a preparation method therefor and pharmaceutically acceptable salts thereof, as well as a use thereof as therapeutic agents, especially uses as angiotensin II type 2 receptor (AT 2 R) antagonists, wherein the definition of each substituent in the general formula (I) is the same as the definition thereof in the description.

First claim

The invention claimed is:

1 . A compound represented by general formula (I):

wherein W, Y and Z are each independently selected from CR n and N, and there are at most 2 N atoms contained among W, Y, and Z;
R 1 is selected from —COOR a and tetrazolyl;
R 2 is selected from 8- to 10-membered heteroaryl and —NR b R c , wherein the heteroaryl is optionally further substituted with one or more substituents selected from R d ;
R 3 is selected from —NR e R f and the group

Y 1 , Y 2 , Y 3 and Y 4 are each independently selected from CR j and N, and there are at most 3 N atoms contained among Y 1 , Y 2 , Y 3 and Y 4 ;
ring A is selected from 6- to 8-membered monocyclic heterocyclyl and 5-membered heteroaryl, wherein the monocyclic heterocyclyl contains one or more N, O or S(O) n therein, and the 6- to 8-membered heterocycle is optionally further substituted by one or more R 10 ;
R a is selected from hydrogen atom and alkyl, wherein the alkyl is optionally further substituted with one or more halogens;
R b is the group:

R c is alkyl;
R e is selected from hydrogen atom and alkyl, wherein the alkyl is optionally further substituted with one or more substituents selected from hydroxyl, alkoxy and halogen;
R f is selected from -L-R k ,
L is selected from C 1-6 alkylene;
wherein the C 1-6 alkylene is substituted or unsubstituted, when the C 1-6 alkylene is substituted, the C 1-6 alkylene is substituted by one or more groups selected from the following: alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylamino, halogen, mercapto, hydroxyl, nitro, cyano, cycloalkyl, heterocyclyl, aryl, heteroaryl, cycloalkoxy, heterocycloalkoxy, cycloalkylthio, heterocycloalkylthio, amino, haloalkyl, hydroxyalkyl, carboxyl, carboxylic ester groups, —C(O)R 4 , —C(O)OR 4 , —OC(O)R 4 , —NR 5 R 6 , —C(O)NR 5 R 6 , —SO 2 NR 5 R 6 and —NR 5 C(O)R 6 ;
R g and R h are each independently selected from hydrogen atom, alkyl, alkoxy, halogen and cyano, wherein the alkyl or alkoxy is optionally further substituted with one or more halogen or alkoxy;
R k is selected from aryl and heteroaryl, wherein the aryl or heteroaryl is optionally further substituted with one or more R m ;
R d , R j , R m , R n and R 10 are the same or different, and are each independently selected from hydrogen atom, hydroxyl, halogen, nitro, cyano, alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, —C(O)R 4 , —C(O)OR 4 , —OC(O)R 4 , —NR 5 R 6 , —C(O)NR 5 R 6 , —S(O) n NR 5 R 6 and —NR 5 C(O)R 6 , wherein the alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally further substituted with one or more substituents selected from hydroxyl, halogen, nitro, cyano, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, ═O, —C(O)R 4 , —C(O)OR 4 , —OC(O)R 4 , —NR 5 R 6 , —C(O)NR 5 R 6 , —SO 2 NR 5 R 6 and —NR 5 C(O)R 6 ;
R 4 , R 5 and R 6 are each independently selected from hydrogen atom, hydroxyl, halogen, nitro, cyano, alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally further substituted with one or more substituents selected from hydroxyl, halogen, nitro, cyano, alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, —C(O)R 7 , —C(O)OR 7 , —OC(O)R 7 , —NR 8 R 9 , —C(O)NR 8 R 9 , —SO 2 NR 8 R 9 and —NR 8 C(O)R 9 ;
or, R 5 and R 6 , together with the N atom connected thereto, form a 4- to 8-membered heterocyclyl, wherein the 4- to 8-membered heterocycle contains one or more N, O or S(O) n , and the 4- to 8-membered heterocycle is optionally further substituted with one or more substituents selected from hydroxyl, halogen, nitro, cyano, alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, ═O, —C(O)R 7 , —C(O)OR 7 , —OC(O)R 7 , —NR 8 R 9 , —C(O)NR 8 R 9 , —SO 2 NR 8 R 9 and —NR 8 C(O)R 9 ;
R 7 , R 8 and R 9 are each independently selected from hydrogen, alkyl, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally further substituted with one or more substituents selected from hydroxyl, halogen, nitro, cyano, alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, carboxyl and carboxylic ester groups;
m is selected from 0, 1, 2, 3, 4 and 5;
n is selected from 0, 1 and 2; and
q is 0, 1, 2, 3, 4 or 5;
a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof.

2 . A compound represented by general formula (II) or a stereoisomer, a tautomer or a pharmaceutically acceptable salt thereof,

wherein W, Y and Z are each independently selected from CH and N, and there is at most 1 N atom contained among W, Y, and Z;
Y 1 , Y 2 , Y 3 and Y 4 are each independently selected from CR j and N, and there is at most 1 N atom contained among Y 1 , Y 2 , Y 3 and Y 4 ;
ring A is selected from 6- to 8-membered monocyclic heterocyclyl, wherein the monocyclic heterocyclyl contains one or more N, O or S(O) n therein, and the 6- to 8-membered heterocycle is optionally further substituted with one or more R 10 ;
R 10 are the same or different, and are each independently selected from halogen, alkyl, alkoxy and ═O, wherein the alkyl or alkoxy is optionally further substituted with halogen;
R j are the same or different, and are each independently selected from hydrogen atom, alkyl, alkoxy and halogen, wherein the alkyl or alkoxy is optionally further substituted with halogen;
q is 0, 1, 2 or 3;
R 1 is selected from —COOR a and tetrazolyl;
R 2 is selected from 8- to 10-membered heteroaryl and —NR b R c , wherein the heteroaryl is optionally further substituted with one or more substituents selected from R d ;
R a is selected from hydrogen atom and alkyl, wherein the alkyl is optionally further substituted with one or more halogens;
R b is the group:

R c is alkyl;
R d is selected from hydrogen atom, hydroxyl, halogen, nitro, cyano, alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, —C(O)R 4 , —C(O)OR 4 , —OC(O)R 4 , —NR 5 R 6 , —C(O)NR 5 R 6 , —S(O) n NR 5 R 6 and —NR 5 C(O)R 6 , wherein the alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally further substituted with one or more substituents selected from hydroxyl, halogen, nitro, cyano, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, ═O, —C(O)R 4 , —C(O)OR 4 , —OC(O)R 4 , —NR 5 R 6 , —C(O)NR 5 R 6 , —SO 2 NR 5 R 6 and —NR 5 C(O)R 6 ;
R 4 , R 5 and R 6 are each independently selected from hydrogen atom, hydroxyl, halogen, nitro, cyano, alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl or heteroaryl is optionally further substituted with one or more substituents selected from hydroxyl, halogen, nitro, cyano, alkyl, alkoxy, cycloalkyl, heterocyclyl, aryl, heteroaryl, —C(O)R 7 , —C(O)OR 7 , —OC(O)R 7 , —NR 8 R 9 , —C(O)NR 8 R 9 , —SO 2 NR 8 R 9 and —NR 8 C(O)R 9 ;
or, R 5 and R 6 , together with the N atom connected thereto, form a 4- to 8-membered heterocyclyl, wherein the 4- to 8-membered heterocycle contains one or more N, O or S(O) n , and th

Assignees

• Zhejiang Hisun Pharm Co Ltd
• Shanghai Aryl Pharmtech Co Ltd

Inventors

• Guo Yanghui
• Liao Weiwei
• Meng Lichen
• Hu taishan
• Chen Lei
• Jiang Guoping

Classifications

• C07D413/14

  containing three or more hetero rings · CPC title

• C07D413/10

  linked by a carbon chain containing aromatic rings · CPC title

• C07D413/04 Primary

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

• C07D267/14

  condensed with one six-membered ring · CPC title

• C07D223/16

  Benzazepines; Hydrogenated benzazepines · CPC title