Pyrazolopyrimidone derivatives and methods of use thereof

Patent metadata

Field	Value
Publication number	US-10633388-B2
Application number	US-201916416418-A
Country	US
Kind code	B2
Filing date	May 20, 2019
Priority date	Oct 30, 2013
Publication date	Apr 28, 2020
Grant date	Apr 28, 2020

Abstract

Pyrazolopyrimidone derivatives and methods of use thereof are described. Specifically, pharmaceutical uses of pyrazolopyrimidone derivatives represented by the general formula (II) and pharmaceutically acceptable salts thereof are described, wherein the definitions of substituents in the general formula (II) are the same as the definitions in the specification. The pyrazolopyrimidone derivatives are useful as gonadotropin releasing hormone (GnRH) antagonists, such as for therapeutic agents for endometriosis.

First claim

We claim:

1. A method for treating uterine leiomyoma, endometriosis, or prostate cancer, the method comprising administering to the subject a pharmaceutical composition comprising an effective amount of a compound of formula (II), or a tautomer, mesomer, racemate, enantiomer, or diastereomer thereof, or mixture thereof, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers, diluents, or excipients:

wherein
R 1 is selected from the group consisting of aryl and heteroaryl, wherein the aryl and heteroaryl are each independently and optionally further substituted with one or more groups selected from the group consisting of halogen, cyano, nitro, alkyl, haloalkyl, hydroxyalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl and —OR 6 ;
R 2 is alkyl, wherein the alkyl is further substituted with aryl, wherein the aryl is optionally further substituted with one or more groups selected from the group consisting of halogen, alkyl, haloalkyl, and —OR 6 ;
R 3 is aryl, wherein the aryl is optionally further substituted with one or more groups selected from the group consisting of halogen, alkyl, haloalkyl, —OR 6 , —C(O)OR 6 , —OC(O)R 6 , —C(O)R 6 , —NHC(O)R 6 , —NHC(O)OR 6 , —NHC(O)NHR 6 , and —NHC(O)NHOR 6 ;
R 4 is alkyl; and
R 5 is hydrogen;
R 6 is selected from the group consisting of hydrogen and alkyl;
n is 1, 2, 3, or 4.

2. The method according to claim 1 , wherein the subject is in need of treatment of prostate cancer.

3. The method according to claim 1 , wherein the subject is in need of treatment of endometriosis.

4. The method according to claim 1 , wherein the compound is selected from the group consisting of:

5. The method according to claim 1 , wherein the subject is in need of treatment of uterine leiomyoma.

6. The method according to claim 2 , wherein the compound is selected from the group consisting of:

7. The method according to claim 3 , wherein the compound is selected from the group consisting of:

8. The method according to claim 1 , wherein the compound is

9. The method according to claim 5 , wherein the compound is

10. The method according to claim 2 , wherein the compound is

11. The method according to claim 3 , wherein the compound is

12. A compound that is

or a tautomer, mesomer, racemate, enantiomer, or diastereomer thereof, or mixture thereof, or a pharmaceutically acceptable salt thereof.

13. The compound of claim 12 , or a pharmaceutically acceptable salt thereof.

14. The method according to claim 1 , wherein R 1 is selected from phenyl or pyridazinyl.

15. The method according to claim 1 , wherein R 2 is benzyl, wherein the benzyl is optionally further substituted with one or more groups selected from the group consisting of halogen, alkyl, —OR 6 and haloalkyl.

16. The method according to claim 1 , wherein R 3 is phenyl, wherein the phenyl is optionally further substituted with one or more groups selected from the group consisting of —NHC(O)R 6 , —NHC(O)OR 6 , —NHC(O)NHR 6 and —NHC(O)NHOR 6 .

17. The method according to claim 1 , wherein R 4 is methyl.

18. The method according to claim 1 , wherein n is 1 or 2.

19. The method according to claim 5 , wherein the compound is selected from the group consisting of:

20. A pharmaceutical composition comprising the compound according to claim 12 , and one or more pharmaceutically acceptable carriers, diluents, or excipients.

21. A pharmaceutical composition comprising the compound according to claim 13 , and one or more pharmaceutically acceptable carriers, diluents, or excipients.

Assignees

• Shanghai hengrui pharmaceutical co ltd
• Jiangsu Hengrui Medicine Co
• Jiangsu Hangrui Medicine Co Ltd

Inventors

• Lu Hejun
• Sun Piaoyang
• Gui Bin
• Dong Qing

Classifications

• A61P17/10

  Anti-acne agents · CPC title

• A61P1/00

  Drugs for disorders of the alimentary tract or the digestive system · CPC title

• A61P5/32

  Antioestrogens · CPC title

• A61P43/00

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

• C07D487/04 Primary

  Ortho-condensed systems · CPC title