Granted Patent B2

US 12,637,474 · App. 17/977,095 · Granted May 26, 2026

Inventors: Tao Yu (Shanghai, CN); Lu Gan (Shanghai, CN); Chengde Wu (Shanghai, CN); Shuhui Chen (Shanghai, CN)

Assignee: Hangzhou Sciwind Biosciences Co., Ltd

C07D495/04

Abstract

Claims (91)

1 . A compound represented by formula (I-B) or a pharmaceutically acceptable salt thereof,

wherein,

is selected from a single bond and a double bond;

T 1 is selected from N, C and CR 6 ;

T 2 is selected from N, C and CH;

T 3 , T 4 , T 5 and T 6 are each independently selected from N and CR 7 ;

X 7 is S and X 5 is CR 8 or CHR 8 ; or

X 7 is CH or CH 2 and X 5 is S;

L 1 is selected from a single bond and —C 1-3 alkyl-;

R 1 is each independently selected from F, Cl, Br, I, OH, NH 2 , CN, C 1-3 alkyl, and C 1-3 alkoxy;

the C 1-3 alkyl and the C 1-3 alkoxy are optionally substituted by 1, 2 or 3 R 1 ′;

R 1 ′ is selected from F, Cl, Br and I;

m is selected from 0, 1, 2, 3, 4 and 5;

R 2 is selected from C 1-3 alkyl,

 and 5- to 6-membered heteroaryl, and the

 C 1-3 alkyl and 5- to 6-membered heteroaryl are optionally substituted by 1, 2 or 3 R a ;

Y 1 and Y 2 are each independently selected from CH, CH 2 , N, NH and O;

o and p are each independently selected from 0, 1, 2 and 3;

R 3 is selected from —C(═O)—NH—R b , —C(═O)—R b , —C(═O)—NH—S(═O) 2 —R b , —S(═O) 2 —NH—R b , —S(═O) 2 —R b , —P(═O)(R b ) 2 , C 1-3 alkyl, tetrazolyl, isoxazolyl,

 the C 1-3 alkyl, tetrazolyl, isoxazolyl,

 are optionally substituted by 1, 2 or 3 R b ;

R 5 is each independently selected from F, Cl, Br, I, OH, C 1-3 alkyl, C 1-3 alkoxy, CN, and C 3-4 cycloalkyl, wherein the C 1-3 alkyl, C 1-3 alkoxy, C 3-4 cycloalkyl are optionally substituted by 1, 2 or 3 R 5 ′;

R 5 ′ is selected from F, Cl, Br, I and OH;

n is selected from 0, 1 and 2;

or, two adjacent R 5 together form C 3-5 cycloalkyl;

R 4 is selected from H, F, Cl, Br, I and CH 3 ;

R 6 is selected from H, F, Cl, Br, I and CH 3 ;

or, R 4 and R 6 combining with the bonds to which they are attached form a double bond or C 3-5 cycloalkyl;

R 7 is each independently selected from H, F, Cl and CN;

R 8 is each independently selected from H, F, Cl and CH 3 ;

R a is selected from F, Cl, Br and I;

R b is selected from OH, CN, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 alkylamino and oxazolyl, and the C 1-3 alkyl, C 1-3 alkoxy and oxazolyl are optionally substituted by 1, 2 or 3 R;

R is selected from F, Cl and Br.

2 . The compound as defined in claim 1 or the pharmaceutically acceptable salt thereof, wherein the compound is represented by formula (P-A):

3 . The compound as defined in claim 2 or the pharmaceutically acceptable salt thereof, wherein, R 2 is selected from

4 . The compound as defined in claim 2 or the pharmaceutically acceptable salt thereof, wherein, (i) R 2 is

L 1 is —CH 2 —;

or,

(ii) R 3 is —COOH;

or,

(iii) the structural moiety

 is selected from

or,

(iv) T 1 is N; T 2 is C or CH;

or,

(v) R 7 is H or F;

or,

(vi) R 1 is each independently selected from F, Cl and CN.

5 . The compound as defined in claim 2 or the pharmaceutically acceptable salt thereof, wherein,

is selected from a single bond and a double bond;

R 8 is each independently selected from H, F, Cl and CH 3 ;

X 7 is S and X 5 is CR 8 ; or

X 7 is CH and X 5 is S;

R 3 is —COOH;

R 2 is

L 1 is selected from a single bond and —C 1-3 alkyl-;

T 1 is N;

T 2 is C or CH;

T 3 is N or CH;

R 7 is each independently selected from H, F, Cl and CN;

R 1 is each independently selected from F, Cl and CN;

m is selected from 0, 1, 2, 3, 4 and 5.

6 . The compound as defined in claim 2 or the pharmaceutically acceptable salt thereof, wherein, the compound is represented by formula (III-Aa):

wherein,

is selected from a single bond and a double bond;

R 8 is H, F or CH 3 ;

X 7 is S and X 5 is CR 8 ; or

X 7 is CH and X 5 is S;

each R 1 is independently selected from F, Cl and CN.

7 . The compound as defined in claim 6 or the pharmaceutically acceptable salt thereof, wherein,

X 5 is CH;

X 7 is S;

each R 1 is independently selected from F, Cl and CN.

8 . The compound as defined in claim 1 or the pharmaceutically acceptable salt thereof, wherein the compound is selected from:

9 . The compound as defined in claim 1 or the pharmaceutically acceptable salt thereof, wherein the compound is selected from:

10 . The compound as defined in claim 1 or the pharmaceutically acceptable salt thereof, wherein the compound is selected from:

11 . The compound as defined in claim 1 or the pharmaceutically acceptable salt thereof, wherein the compound is

12 . The compound as defined in claim 1 or the pharmaceutically acceptable salt thereof, wherein the compound is

13 . A method for preparing the compound as defined in claim 1 , the method comprises the following step, in a solvent, in the presence of catalyst, the following reaction is carried out to obtain the compound represented by formula (I-B),

wherein, the solvent is selected from one or more than one of water, acetonitrile, methanol and tetrahydrofuran;

the catalyst is [1,5,7]-triazidobicyclo [4.4.0]decan-5-ene or lithium hydroxide monohydrate;

Rx is methyl or ethyl;

X 5 , X 7 , R 2 , L 1 , R 4 , T 1 , T 2 , T 3 , T 4 , T 5 , T 6 , R 5 , n, R 1 and m are as defined in claim 1 .

14 . A compound represented by formula (I-A),

wherein, Rx is methyl or ethyl;

X 5 , X 7 , R 2 , L 1 , R 4 , T 1 , T 2 , T 3 , T 4 , T 5 , T 6 , R 5 , n, R 1 and m are as defined in claim 1 .

15 . A pharmaceutical composition comprising the compound as defined in claim 1 and a pharmaceutically acceptable carrier.

16 . A method for activating GLP-1 receptor in a subject in need thereof, comprising administering to the subject an effective amount of the compound as defined in claim 1 or the pharmaceutically acceptable salt thereof.

17 . A method for treating a disease related to GLP-1 receptor in a subject in need thereof, comprising administering to the subject an effective amount of the compound as defined in claim 1 or the pharmaceutically acceptable salt thereof, wherein the disease is type II diabetes.

18 . A method for activating GLP-1 receptor in a subject in need thereof, comprising administering to the subject an effective amount of the pharmaceutical composition as defined in claim 15 .

19 . A method for treating a disease related to GLP-1 receptor in a subject in need thereof, comprising administering to the subject an effective amount of the pharmaceutical composition as defined in claim 15 , wherein the disease is type II diabetes.

Assignments (1)

Priority Claims (3)

Continuity (3)

References Cited (18)