PYRROLOTRIAZINE ANILINE PRODRUG COMPOUNDS USEFUL AS KINASE INHIBITORS

Abstract

Compounds having the Formula (I), including pharmaceutically acceptable salts thereof,

Description

Claims

1. A compound of Formula I:

2. The compound of claim 1, wherein k is 1 or 2.

3. The compound of claim 1, wherein A1 is selected from optionally-substituted C1-C6 alkyl, optionally-substituted C1-C6 cycloalkyl and optionally-substituted C1-C6 heteroaryl.

4. The compound of claim 1, wherein A1 is ethyl.

5. The compound of claim 1, wherein A1 is propyl.

6. The compound of claim 1, wherein A1 is cyclopropyl.

7. The compound of claim 1, wherein A1 is iso-oxazole.

8. The compound of claim 1, wherein A2 is selected from optionally substituted C1-C6 alkyl and optionally-substituted C1-C6 cycloalkyl.

9. The compound of claim 1, wherein A2 is ethyl.

10. The compound of claim 1, wherein A2 is propyl.

11. The compound of claim 1, wherein A2 is cyclopropyl.

12. The compound of claim 1, wherein R1, R3 and R5 are independently selected from hydrogen and optionally-substituted C1-C4 alkyl.

13. The compound of claim 1, wherein R1 and R5 are each hydrogen and R3 is methyl.

14. The compound of claim 1, wherein le is selected from hydrogen and C1-C4 alkyl.

15. A pharmaceutical composition, which comprises a pharmaceutically effective amount of a compound of Formula I, including pharmaceutically acceptable salts thereof, as claimed in claim 1, and one or more pharmaceutically acceptable carriers, excipients or diluents.

16. A method of treating an inflammatory disorder comprising administering to a patient in need of such treatment a pharmaceutical composition according to claim 15.

17. The method of claim 16, wherein the inflammatory disorder is selected from asthma, adult respiratory distress syndrome, chronic obstructive pulmonary disease, chronic pulmonary inflammatory disease, diabetes, inflammatory bowel disease, Alzheimer's disease, osteoporosis, psoriasis, graft vs. host rejection, atherosclerosis, multiple myeloma, pain, myocardial ischemia and arthritis, including rheumatoid arthritis, psoriatic arthritis, traumatic arthritis, rubella arthritis, gouty arthritis and osteoarthritis.

18. The compound of claim 1, wherein the salts are selected from sodium salts, potassium salts, calcium salts, magnesium salts, lithium salts, hydrogen chloride salts and methane sulfonic acid salts.

19. The use of a carbamate substituted pyrrolotriazine compound of Formula I of claim 1 as a prodrug for releasing a parent drug containing the substituted pyrrolotriazine compound after removal of the carbamate moiety in animals or humans.

20. A compound having the Formula II:

21. The compound of claim 20, wherein R7 is

22. The compound of claim 20, wherein R7 is

23. The compound of claim 20, wherein R7 is