[1,2,4]triazolo[1,5-c]pyrimidine derivative as A2A receptor inhibitor

Patent metadata

Field	Value
Publication number	US-11117899-B2
Application number	US-201816500901-A
Country	US
Kind code	B2
Filing date	Apr 8, 2018
Priority date	Apr 7, 2017
Publication date	Sep 14, 2021
Grant date	Sep 14, 2021

Abstract

Provided are a compound represented by formula (I), an isomer or a pharmaceutically acceptable salt thereof, and an application of the same in preparing a drug for treating a disease related to A 2A receptor. The R 1 , R 2 , R 3 , ring A, ring B, n, and m are as defined in the specification.

First claim

The invention claimed is:

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

wherein
R 1 is selected from the group consisting of H, CN, COOH, and

or is selected from the group consisting of C 1-3 alkyl, C 1-3 alkyl-O—C 1-3 alkyl-, C 1-3 alkyl-C(=O)NH-, and C 3-6 cycloalkyl, each of which is optionally substituted by 1, 2 or 3 R;
R 2 is each independently selected from the group consisting of H, F, Cl, Br, I, OH, NH 2 , and CN, or is independently selected from the group consisting of C 3-6 cycloalkyl, C 1-6 alkyl, and C 1-6 heteroalkyl, each of which is optionally substituted by 1, 2 or 3 R;
R 3 is each independently selected from the group consisting of H, F, Cl, Br, I, OH, NH 2 , and CN, or is independently selected from the group consisting of C 1-6 alkyl or C 1-6 heteroalkyl, each of which is optionally substituted by 1, 2 or 3 R;
n is 0, 1, 2 or 3;
m is 0, 1, 2 or 3;
ring A is selected from the group consisting of 6- to 10-membered aryl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl and 5- to 10-membered heterocycloalkenyl;
ring B is selected from the group consisting of phenyl and 5- to 6-membered heteroaryl;
R is selected from the group consisting of F, Cl, Br, I, OH, NH 2 , and CN, or is selected from the group consisting of C 1-3 alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkyl-NH—, 3- to 6-membered heterocycloalkyl, 3- to 6-membered heterocycloalkyl-O-, and phenyl, each of which is optionally substituted by 1, 2 or 3 R′;
R′ is selected from the group consisting of F, Cl, Br, I, OH, NH 2 , Me, and

the heteroatom or the heteroatom group of the C1-6 heteroalkyl, 5- to 10-membered heteroaryl, 5- to 10-membered heterocycloalkyl, 3- to 6-membered heterocycloalkyl and 5- to 10-membered heterocycloalkenyl is each independently selected from the group consisting of N, O, S, NH, —C(═O)—, —C(═O)O- and —C(═O)NH—;
the number of the heteroatom or the heteroatom group is each independently 1, 2, 3 or 4.

2. The compound, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R is selected from the group consisting of F, Cl, Br, I, OH, NH 2 , and CN, or is selected from the group consisting of Me, Et,

each of which is optionally substituted by 1, 2 or 3 R′.

3. The compound, or a pharmaceutically acceptable salt thereof according to claim 2 , wherein R is selected from the group consisting of F, Cl, Br, I, OH, NH 2 , CN,
Me, Et,

4. The compound, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R 1 is selected from the group consisting of H, CN, COOH, and

or is selected from the group consisting of Me, Et,

each of which is optionally substituted by 1, 2 or 3 R.

5. The compound, or a pharmaceutically acceptable salt thereof according to claim 4 , wherein R 1 is selected from the group consisting of H, CN, COOH, Me, Et,

6. The compound, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R 2 is each independently selected from the group consisting of H, F, Cl, Br, I, OH NH 2 , and CN, or is independently selected from the group consisting of C 3-6 cycloalkyl, C 1-3 alkyl and C 1-3 alkoxy, each of which is optionally substituted by 1, 2 or 3 R.

7. The compound, or a pharmaceutically acceptable salt thereof according to claim 6 , wherein R 2 is each independently selected from the group consisting of H, F, Cl, Br, I, OH, NH 2 , CN, Me, Et, CF 3 ,

8. The compound, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R 3 is each independently selected from the group consisting of H, F, Cl, Br, I, OH, NH 2 , and CN, or is independently selected from the group consisting of C 1-3 alkyl and C 1-3 alkoxy, each of which is optionally substituted by 1, 2 or 3 R.

9. The compound, or a pharmaceutically acceptable salt thereof according to claim 8 , wherein R 3 is each independently selected from the group consisting of H, F, Cl, Br, I, OH, NH 2 , CN, Me, Et, CF 3 and

10. The compound, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein ring A is selected from the group consisting of phenyl, pyridyl, tetrahydropyranyl, 3,6-dihydro-2H-pyranyl, piperidinyl, 1,2,3,6-tetrahydropyridyl, 1H-indolyl, 1H-indazolyl, 1H-benzo[d]imidazolyl, benzo[d][1,3 dioxolyl, indolin-2-onyl, 1H-benzo[d][1,2,3]triazolyl, quinolinyl and 1,2,3,4-tetrahydroquinolinyl.

11. The compound, or a pharmaceutically acceptable salt thereof according to claim 10 , wherein the moiety

is selected from the group consisting of

12. The compound, or a pharmaceutically acceptable salt thereof according to claim 11 , wherein the moiety

is selected from the group consisting of

13. The compound, or a pharmaceutically acceptable salt thereof according to claim 12 , wherein the moiety

is selected from the group consisting of

14. The compound, or a pharmaceutically acceptable salt thereof according to claim 1 , wherein ring B is selected from the group consisting of phenyl, pyridyl, imidazolyl, pyrazolyl, furyl, thienyl, and thiazolyl.

15. The compound, or a pharmaceutically acceptable salt thereof according to claim 14 , wherein the moiety

is selected from the group consisting of

16. The compound, or a pharmaceutically acceptable salt thereof according to claim 15 , wherein the moiety

is selected from the group consisting of

17. The compound,

Assignees

• Medshine Discovery Inc

Inventors

• Chen Kevin X
• Yu Yanxin
• Chen Xinde
• Zhang Li
• Chen Zhaoguo
• Xie Cheng
• Wang Xiaofei
• Wu Linghui
• Hu Guoping
• Li Jian
• Chen Shuhui

Classifications

• A61P35/00 Primary

  Antineoplastic agents · CPC title

• C07D487/04 Primary

  Ortho-condensed systems · CPC title

• A61P25/16

  Anti-Parkinson drugs · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title