Heterobicyclic compounds useful as kinase inhibitors

• US 8,309,571 B2
• Filed: 04/12/2011
• Issued: 11/13/2012
• Est. Priority Date: 11/27/2006
• Status: Active Grant

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Dhar, T. G. Murali, Wrobleski, Stephen T.
• Primary Examiner(s): MURRAY, JEFFREY H
• Application Number:
  US13/084,622
• Publication Number:
  US 20110190292A1
• Time in Patent Office: 581 Days
• Field of Search: None
• US Class Current: 514/303
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

A compound of Formula (I)

and enantiomers, diastereomers and pharmaceutically-acceptable salts thereof. Also disclosed are pharmaceutical compositions containing compounds of Formula I, and methods of treating conditions associated with the activity of p38 kinase.

Claims

1. A compound of Formula (I):

2. A compound according to claim 1 wherein;

R¹ is selected from the group consisting of halo and haloalkyl, wherein the haloalkyls have 1-3 carbons and 1-5 halogens;

R² is —

[C(O)]₂NR⁷R⁸, wherein each of R⁷ and R⁸ is independently selected to be H or an optionally substituted C_1-6 alkyl, or R⁷ and R⁸ can be taken together with the carbons to which they are attached to form an optionally substituted 5-6 membered ring;

R³ is selected from the group consisting of hydrogen and C1-C3 alkyl;

R⁴ is selected from the group consisting of hydrogen, CO₂R¹¹, and CONR¹¹R¹² —

wherein each of R¹¹ and R¹² are independently selected from the group consisting of H, C1-C6 straight or branched chain alkyl, C1-C4 straight or branched chain alkyl amino, C1-C4 straight or branched chain dialkyl amino, C1-C4 straight or branched chain alkyl with an OH group; and

C4-C10 heterocyclo with 1-3 members selected from the group consisting of N, S and O, provided there are no O—

O or S—

S bonds in R⁴ and the heterocyclo group can be optionally substituted with a member selected from the group consisting of C1-C4 alkyl, optionally substituted amino, and alkyl amino;

B is —

(CR⁵R⁶)_q—

wherein R⁵ and R⁶ are each independently selected from the group consisting of H and optionally substituted C1-C4 alkyl;

ring A is selected from the group consisting of phenyl, indole, indazole, and benzimidazole;

m is 0-2;

n is 0-2; and

q is 0.

3. A compound according to claim 1 wherein:

Q is a bond when L is —

C═ and

M is —

N—

;

q is 0;

R¹ is halo;

R² is —

[C(O)]₂NR⁷R⁸;

R³ is hydrogen;

R⁴ is hydrogen or —

C(O)NR¹¹R¹²;

ring A is selected from the group consisting of phenyl, indole, indazole, benzimidazole, pyrrolo[2,3-b]pyridine and 2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole.

4. A compound according to claim 1 selected from the group consisting of:

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