Heterocyclic compounds and uses thereof

• US 9,255,108 B2
• Filed: 12/17/2014
• Issued: 02/09/2016
• Est. Priority Date: 04/10/2012
• Status: Active Grant

• Current Assignee: Infinity Pharmaceuticals, Inc.
• Original Assignee: Infinity Pharmaceuticals, Inc.
• Inventors: Castro, Alfredo C., Chan, Katrina, Evans, Catherine A., Janardanannair, Somarajannair, Lescarbeau, Andre, Li, Liansheng, Liu, Tao, Liu, Yi, Ren, Pingda, Snyder, Daniel A., Tremblay, Martin R.
• Primary Examiner(s): Pagano, Alexander R
• Application Number:
  US14/573,961
• Publication Number:
  US 20150105385A1
• Time in Patent Office: 419 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 Antimigraine agents
• 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 25/28 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 7/06 : Antianaemics
• 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 217/24 : Oxygen atoms
• CPC Class Codes: C07D 217/26 : Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07D 401/04 : directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 : containing three or more hetero rings
• CPC Class Codes: C07D 403/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/14 : containing three or more hetero rings
• CPC Class Codes: C07D 471/04 : Ortho-condensed systems
• CPC Class Codes: C07D 487/04 : Ortho-condensed systems
• CPC Class Codes: C07D 491/048 : the oxygen-containing ring being five-membered
• CPC Class Codes: C07D 491/056 : with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
• CPC Class Codes: C07D 495/04 : Ortho-condensed systems
• CPC Class Codes: C07D 513/04 : Ortho-condensed systems
• CPC Class Codes: C07D 519/00 : Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including PI3 kinase activity, are described herein.

Claims

1. A method of treating a solid tumor, an inflammatory disease, or an auto-immune disease in a subject, comprising administering to said subject a therapeutically effective amount of a compound of Formula (I):

2. The method of claim 1, wherein the compound of Formula (I) is a compound of Formula (IIIb):

3. The method of claim 1, wherein the compound of Formula (I) is a compound of Formula (II):

4. The method of claim 1, wherein R³ is halo, cyano, hydroxy, alkyl, alkoxy, amino, acyl, heteroaryl, aryl, heterocyclyl, or cycloalkyl.

5. The method of claim 4, wherein R³ is heteroaryl, aryl, alkyl, haloalkyl, OH, Cl, or F.

6. The method of claim 5, wherein R³ is heteroaryl, phenyl, CH₃, CF₃, OH, or Cl.

7. The method of claim 1, wherein R⁸ is H, CH₃, OCH₃, CF₃, CN, or halo.

8. The method of claim 1, wherein B is aryl, heteroaryl, alkyl, cycloalkyl, or heterocyclyl, each of which is substituted with 0, 1, 2, or 3 occurrence(s) of R².

9. The method of claim 1, wherein B is unsubstituted phenyl.

10. The method of claim 1, wherein B is phenyl substituted with 1 or 2 occurrence(s) of R².

11. The method of claim 10, wherein R² is halo or alkyl.

12. The method of claim 1, wherein B is methyl, isopropyl, or cyclopropyl.

13. The method of claim 1, wherein W_d is:

14. The method of claim 1, wherein W_d is:

15. The method of claim 1, wherein W_d is:

16. The method of claim 1, wherein W_d is:

17. The method of claim 1, wherein W_d is

18. The method of claim 13, wherein R¹⁰ is NH₂.

19. The method of claim 1, wherein X is —

CH(CH₃)—

.

20. The method of claim 19, wherein the CH carbon of the —

CH(CH₃)—

moiety has an (S) stereochemical configuration.

21. The method of claim 1, wherein Y is —

NH—

C(O)—

.

22. The method of claim 1, wherein —

X—

Y—

is —

CH₂—

N(CH₃)—

C(O)—

.

23. The method of claim 1, wherein —

X—

Y—

is (S)—

CH(CH₃)—

NH—

C(O)—

.

24. The method of claim 1, wherein the compound is

25. The method of claim 1, wherein the compound is

26. The method of claim 1, wherein the compound is

27. The method of claim 1, wherein the compound is

28. The method of claim 1, wherein the compound is

29. The method of claim 1, wherein the compound is

32. The method of claim 1, which is a method of treating a solid tumor.

33. The method of claim 32, wherein the solid tumor is prostate cancer, breast cancer, or glioblastoma.

34. The method of claim 32, wherein the solid tumor is a skin cancer.

35. The method of claim 34, wherein the skin cancer is melanoma.

36. The method of claim 32, wherein the solid tumor is lung cancer.

37. The method of claim 36, wherein the lung cancer is non-small cell lung cancer.

38. The method of claim 32, wherein the solid tumor is colon cancer, head and neck cancer, renal cell carcinoma, bladder cancer, ovarian cancer, or pancreatic cancer.

39. The method of claim 32, wherein the solid tumor is a solid tumor metastasis to bone marrow.

40. The method of claim 1, wherein the inflammatory bowel disease is Crohn'"'"'s disease, ulcerative colitis, collagenous colitis, lymphocytic colitis, ischaemic colitis, diversion colitis, Behcet'"'"'s syndrome, or indeterminate colitis.

41. The method of claim 1, further comprises administering to the subject one or more of chemotherapeutic agents, cytotoxic agents, radiation, immuno-modulators, antibodies, or BTK inhibitors.

42. The method of claim 41, wherein the antibody is anti-CD20 antibodies.

43. The method of claim 41, wherein the BTK inhibitor is ibrutinib.

44. The method of claim 1, further comprises administering to the subject rituximab, bendamustine, chlorambucil, fludarabine, cyclophosphamide, or chlorambucil, or a combination thereof.

45. The method of claim 1, further comprises administering to the subject fludarabine, cyclophosphamide, or rituximab, or a combination thereof.

30. A method of treating a solid tumor, an inflammatory disease, or an auto-immune disease in a subject, comprising administering to said subject a therapeutically effective amount of a compound of Formula (II):

31. The method of claim 30, wherein the compound is