Compounds

Novel pyridin-4-yl or pyrimidin-4-yl substituted pyridine compounds and compositions for use in therapy.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 demonstrates the mitogen-activated protein kinase (MAP) kinase cascade.

FIG. 2 demonstrates the p38 kinase pathway.

1. A compound of the formula

wherein

2. The compound according to claim 1 wherein Y is nitrogen.

3. The compound according to claim 2 wherein the R

1 substituent is X—R

a or amino.

4. The compound according to claim 3 wherein R

a is alkyl, or an optionally substitued aryl.

5. The compound according to claim 1 wherein R

4 is an optionally substituted phenyl.

6. The compound according to claim 5 wherein the phenyl is substituted one or more times independently by halogen, SR

5, S(O)R

5, OR

12, halo-substituted-C

1-4 alkyl, or C

1-4 alkyl.

7. The compound according to claim 1 wherein R

2 is hydrogen.

8. The compound according to claim 1 wherein R

3 is hydrogen.

9. The compound according to claim 1 wherein R

5 is hydrogen.

10. The compound according to claim 1 wherein R

2, R

3 and R

5 are hydrogen.

11. The compound according to claim 1 which is

or a pharmaceutically acceptable salt thereof.

12. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier or diluent.

13. A method of treating a CSBP/RK/p38 kinase mediated disease, in a mammal in need thereof, which comprises administering to said mammal an effective amount of a compound of Formula (I) according to claim 1.

14. The method according to claim 13 wherein the CBSP/RKp38 kinase mediated disease is psoriatic arthritis, Reiter's syndrome, rheumatoid arthritis, gout, traumatic arthritis, rubella arthritis and acute synovitis, rheumatoid spondylitis, osteoarthritis, gouty arthritis and other arthritic condition, sepsis, septic shock, endotoxic shock, gram negative sepsis, toxic shock syndrome, Alzheimer's disease, stroke, ischemic and hemorrhagic stroke, neurotrauma/closed head injury, asthma, adult respiratory distress syndrome, chronic obstructive pulmonary disease, cerebral malaria, meningitis, chronic pulmonary inflammatory disease, silicosis, pulmonary sarcososis, bone resorption disease, osteoporosis, restenosis, cardiac reperfusion injury, brain and renal reperfusion injury, chronic renal failure, thrombosis, plomerularonephritis, diabetes, diabetic retinopathy, macular degeneration, graft vs. host reaction, allograft rejection, inflammatory bowel disease, Crohn's disease, ulcerative colitis, neurodegenrative disease, multiple sclerosis, muscle degeneration, diabetic retinopathy, macular degeration, tumor growth and metastasis, angiogenic disease, rhinovirus infection, gingivitis, periodontitis, eczema, contact dermatitis, psoriasis, sunburn, and conjunctivitis.

15. The compound according to claim 1 wherein Y is carbon.

16. A pharmaceutical composition comprising a compound according to claim 11 and a pharmaceutically acceptable carrier or diluent.

17. THe compound according to claim 16 wherein the R

1 substituent is X-R

a or amino.

18. The compound according to claim 17 wherein R

a is alkyl, or an optically substitued aryl.