Pyrrolo[2,3-D]pyrimidines as inhibitors of Janus kinases

• US 8,580,802 B2
• Filed: 09/28/2006
• Issued: 11/12/2013
• Est. Priority Date: 09/30/2005
• Status: Expired due to Fees

• Current Assignee: Vertex Pharmaceuticals Incorporated
• Original Assignee: Vertex Pharmaceuticals Incorporated
• Inventors: Salituro, Francesco, Farmer, Luc, Wang, Tiansheng, Wang, Jian, Bethiel, Randy, Wannamaker, Marion, Martinez-Botella, Gabriel, Duffy, John, Aronov, Alexander, Lauffer, David, Pierce, Albert
• Primary Examiner(s): Moore, Susanna
• Application Number:
  US11/528,779
• Publication Number:
  US 20070207995A1
• Time in Patent Office: 2,602 Days
• Field of Search: 544/280, 514/265.1
• US Class Current: 514/265.1
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/14 for baldness or alopecia
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• 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 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• 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

The present invention relates to compounds of the following structural formula:

which are useful as inhibitors of protein kinases, particularly of JAK family kinases. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.

Claims

1. A compound having the formula:

2. The compound according to claim 1, wherein J^Q is

3. The compound according to claim 2, wherein J^Q is

4. The compound according to claim 3, wherein R⁸ is selected from

5. The compound according to claim 2, wherein r is 0 and R′

, R⁸, and the intervening carbon together are

6. The compound according to claim 2, wherein each of Z¹ and Z² is N.

7. The compound according to claim 2, wherein R″

is CF₃, CH₂CF₃ or CH₂CH₂CF₃.

8. The compound according to claim 1 having the formula:

9. The compound according to claim 8, wherein Z² is CH.

10. The compound according to claim 8, wherein Z² is N.

11. The compound according to claim 8, wherein Z³ is C-J^Q3.

12. The compound according to claim 11, wherein J^Q3 is F.

13. The compound according to claim 11, wherein J^Q3 is H.

14. The compound according to claim 8, wherein Z³ is N.

15. The compound according to claim 14, wherein Z² is N.

16. The compound according to claim 8, wherein J^Q2 is hydrogen.

17. The compound according to claim 8, wherein J^Q2 is —

C(O)OH, —

C(O)OR″

, —

C(O)R″

, —

C(O)NHR″

, —

C(O)N(R)R″

, —

C(O)N(R)R⁹R″

, —

CN, or —

R″

, wherein J^Q2 is optionally substituted with up to two occurrences of J^V.

18. The compound according to claim 8, wherein J^Q1 is

19. The compound according to claim 18, wherein J^Q1 is

20. The compound according to claim 19, wherein R⁸ is selected from

21. The compound according to claim 18, wherein J^Q1 is

22. The compound according to claim 18, wherein J^Q1 is

23. The compound according to claim 22, wherein R′

, R⁸, and the intervening carbon together are

24. The compound according to claim 18, wherein R″

is CF₃, CH₂CF₃, or CH₂CH₂CF₃.

25. The compound according to claim 1, wherein said compound is selected from:

26. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier, adjuvant, or vehicle.