Thieno[3,2-d]pyrimidine, furo[3,2-d]pyrimidine, and pyrrolo[3,2-D]pyrimidines useful for treating respiratory syncitial virus infections

Patent metadata

Field	Value
Publication number	US-10179794-B2
Application number	US-201715717493-A
Country	US
Kind code	B2
Filing date	Sep 27, 2017
Priority date	Jul 28, 2014
Publication date	Jan 15, 2019
Grant date	Jan 15, 2019

Abstract

Provided herein are formulations, methods and substituted thieno[3,2-d]pyrimidine, furo[3,2-d]pyrimidine, and pyrrolo[3,2-d]pyrimidine compounds of Formula (I) for treating Pneumovirinae virus infections, including respiratory syncytial virus infections, as well as methods and intermediates for synthesis of substituted thieno[3,2-d]pyrimidine, furo[3,2-d]pyrimidine, and pyrrolo[3,2-d]pyrimidine compounds.

First claim

What is claimed:

1. A compound of Formula (III), or a pharmaceutically acceptable salt thereof:

wherein:
R 2 is F, Cl, or OH;
R 3 is selected from the CN and N 3 ; and
R 4 is H or

wherein W 1 and W 2 are each, independently, OH or a group of the Formula Ia:

wherein:
each Y is independently a bond or 0;
m is 0, 1, 2, or 3;
each R x is H, halogen or OH;
or

R 4 is selected from H and

wherein:
R 7 is selected from C 1 -C 8 alkyl, —O—C 1 -C 8 alkyl, benzyl, —O-benzyl, —CH 2 —C 3 -C 6 cycloalkyl, —O—CH 2 —C 3 -C 6 cycloalkyl, and CF 3 ;
R 8 is phenyl;
R 9 is selected from H and CH 3 ;
R 10 is selected from H and C 1 -C 6 alkyl; and
R 11 is selected from H and C 1 -C 8 alkyl.

2. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is selected from the group of:

3. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is:

R 8 , R 9 , R 10 , and R 11 are as defined in claim 1 .

4. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 4 is:

5. A compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is F or OH.

6. A compound of claim 1 selected from the group of:

or a pharmaceutically acceptable salt thereof.

7. A compound of claim 1 selected from the group of:

or a pharmaceutically acceptable salt thereof.

8. A compound of claim 1 wherein the compound is

or a pharmaceutically acceptable salt thereof.

9. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

10. A pharmaceutical composition comprising a compound of claim 6 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

11. A pharmaceutical composition comprising a compound of claim 7 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

12. A pharmaceutical composition comprising a compound of claim 8 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

13. A method of treating Pneumovirinae virus infection in a human in need thereof, the method comprising administering to the human a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

14. The method of claim 13 , wherein the Pneumovirinae virus infection is a respiratory syncytial virus infection.

15. A method of treating Pneumovirinae virus infection in a human in need thereof, the method comprising administering to the human a therapeutically effective amount of a compound of claim 6 , or a pharmaceutically acceptable salt thereof.

16. The method of claim 15 , wherein the Pneumovirinae virus infection is a respiratory syncytial virus infection.

17. A method of treating Pneumovirinae virus infection in a human in need thereof, the method comprising administering to the human a therapeutically effective amount of a compound of claim 7 , or a pharmaceutically acceptable salt thereof.

18. The method of claim 17 , wherein the Pneumovirinae virus infection is a respiratory syncytial virus infection.

19. A method of treating Pneumovirinae virus infection in a human in need thereof, the method comprising administering to the human a therapeutically effective amount of a compound of claim 8 , or a pharmaceutically acceptable salt thereof.

20. The method of claim 19 , wherein the Pneumovirinae virus infection is a respiratory syncytial virus infection.

Assignees

• Gilead Sciences Inc

Inventors

• Clarke Michael O'Neil Hanrahan
• Mackman Richard L
• Siegel Dustin

Classifications

• A61P31/14

  for RNA viruses · CPC title

• A61P31/16

  for influenza or rhinoviruses · CPC title

• A61P31/12

  Antivirals · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• C07H7/06

  Heterocyclic radicals · CPC title