Thieno[3,2-d]pyrimidines derivatives for the treatment of viral infections

Patent metadata

Field	Value
Publication number	US-9556199-B2
Application number	US-201414908237-A
Country	US
Kind code	B2
Filing date	Jul 29, 2014
Priority date	Jul 30, 2013
Publication date	Jan 31, 2017
Grant date	Jan 31, 2017

Abstract

This invention relates to thieno[3,2-d]pyrimidines derivatives, processes for their preparation, pharmaceutical compositions, and their use in treating viral infections.

First claim

The invention claimed is:

1. A compound of formula (I)

or a pharmaceutically acceptable salt, tautomer(s), stereo-isomeric form, or solvate thereof, wherein
R 1 is selected from the group consisting of hydrogen, halogen, —CH 3 and —CF 3 ;
R 2 is selected from the group consisting of hydrogen, halogen, C 1-6 alkyl and C 3-6 cycloalkyl;
R 3 is C 1-8 alkyl optionally substituted by one or more substituents independently selected from the group consisting of aryl, aryloxy, halogen, hydroxyl, alkylamino, dialkylamino, C 1-6 alkenyl, C 1-6 alkoxy, —CO 2 H, —CO 2 C 1-6 alkyl, —CO 2 NH 2 , —CN, —SO 2 NHC 1-3 alkyl, —NHSO 2 C 1-3 alkyl, —NH(SO 2 )NH 2 , and —SO 2 N(H)(COC 1-6 alkyl; or
R 3 is an alkylaryl optionally substituted by one or more substituents independently selected from the group consisting of aryl, aryloxy, halogen, alkylamino, dialkylamino, C 1-6 alkyl, C 1-6 alkenyl, C 1-6 alkoxy, —CO 2 H, —CO 2 C 1-6 alkyl, —CO 2 NH 2 , —CN, —SO 2 NHC 1-3 alkyl, —NHSO 2 C 1-3 alkyl, —NH(SO 2 )NH 2 , and —C(O)NHSO 2 C 1-3 alkyl.

2. A compound according to claim 1 wherein R 1 and R 2 are both hydrogen and wherein R 3 is C 1-8 alkyl substituted by hydroxyl.

3. A compound according to claim 2 having the structure

4. A pharmaceutical composition comprising a compound according to claim 1 together with one or more pharmaceutically acceptable excipients, diluents or carriers.

5. A method of treating a disorder in which the modulation of TLR 7 and/or TLR 8 is involved, comprising the administration of a therapeutically effective amount of at least one compound of claim 1 .

6. The method of claim 5 , wherein the disorder is a viral infection.

7. A compound according to claim 1 having the structure

8. A compound according to claim 1 , wherein R 2 is H, CH 3 or C(CH 3 ) 3 .

9. A compound according to claim 1 , wherein R 3 is selected from the group consisting of

10. A compound according to claim 1 wherein R 1 is H and R 2 is CH 3 .

11. A compound according to claim 1 wherein R 1 is CH 3 and R 2 is H.

12. A compound according to claim 1 wherein R 1 and R 2 are H.

13. A compound according to claim 1 , wherein R 3 is selected from the group consisting of

14. A compound according to claim 1 , wherein R 3 is

15. A compound according to claim 1 , wherein said compound is selected from the group consisting of

16. A compound as claimed in claim 15 , selected from the group consisting of

17. A pharmaceutical composition comprising a compound according to claim 15 together with one or more pharmaceutically acceptable excipients, diluents or carriers.

18. A method of treating a disorder in which the modulation of TLR 7 and/or TLR 8 is involved, comprising the administration of a therapeutically effective amount of at least one compound as claimed in claim 15 .

19. The method of claim 18 , wherein the disorder is a viral infection.

20. A method of preparing a compound of claim 1 , wherein said method comprises:
mixing intermediate I with cyanamide in a polar solvent containing acid to form intermediate II

and
mixing intermediate II with a peptide coupling reagent or a chlorinating agent in combination with a base and an amine in a polar solvent to form the compound of claim 1 .

Assignees

• Janssen Sciences Ireland Uc

Inventors

• Mcgowan David Craig
• Raboisson Pierre Jean-Marie Bernard

Classifications

• A61P37/04

  Immunostimulants · CPC title

• A61P43/00

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

• A61P37/02

  Immunomodulators · CPC title

• A61P31/12

  Antivirals · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title