Heterocyclic compounds and uses thereof

• US 8,940,742 B2
• Filed: 03/15/2013
• Issued: 01/27/2015
• 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): Wilson, James O
• Assistant Examiner(s): Pagano, Alexander R
• Application Number:
  US13/841,265
• Publication Number:
  US 20130267521A1
• Time in Patent Office: 683 Days
• Field of Search: 514/248, 514/255.05, 514/259.3, 514/300, 514/309, 544/236, 544/281, 544/405, 546/122, 546/123
• US Class Current: 514/248
• 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 compound of Formula (I):

2. The compound of claim 1, having Formula (IIIb):

3. The compound of claim 1, having a structure of Formula (II):

4. The compound of claim 1, having a structure of Formula (IIIa) or Formula (IIIb):

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

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

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

8. The compound of claim 5, wherein R³ is CH₃, OCH₃, CF₃, or halo.

9. The compound of claim 5, wherein R³ is OCF₃, CN, cyclopropyl, CH₂OH, amino, formyl, or heterocyclyl.

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

11. The compound 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.

12. The compound of claim 1, wherein B is phenyl substituted with 0, 1, 2, or 3 occurrence(s) of R².

13. The compound of claim 1, wherein B is unsubstituted phenyl.

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

15. The compound of claim 14, wherein R² is halo or alkyl.

16. The compound of claim 1, wherein B is methyl, isopropyl, or cyclopropyl.

17. The compound of claim 1, wherein B is cyclohexyl or alkyl.

18. The compound of claim 1, wherein W_d is:

19. The compound of claim 1, wherein W_d is:

20. The compound of claim 1, wherein W_d is:

21. The compound of claim 1, wherein W_d is:

22. The compound of claim 1, wherein W_d is:

23. The compound of claim 1, wherein W_d is:

24. The compound of claim 1, wherein W_d is

25. The compound of claim 18, wherein R¹⁰ is NH₂.

26. The compound of claim 1, wherein X is —

CH₂—

or —

CH(CH₃)—

.

27. The compound of claim 26, wherein X is —

CH(CH₃)—

.

28. The compound of claim 27, wherein the CH carbon of the —

CH(CH₃)—

moiety has an (S) stereochemical configuration.

29. The compound of claim 27, wherein the CH carbon of the —

CH(CH₃)—

moiety has an (R) stereochemical configuration.

30. The compound of claim 1, wherein Y is —

NH—

C(O)—

.

31. The compound of claim 1, wherein —

X—

Y—

is —

CH₂—

N(CH₃)—

C(O)—

.

32. The compound of claim 1, wherein —

X—

Y—

is (S)—

CH(CH₃)—

NH—

C(O)—

.

33. The compound of claim 1, wherein —

X—

Y—

is (R)—

CH(CH₃)—

NH—

C(O)—

.

34. A pharmaceutical composition comprising a compound of claim 1, and a pharmaceutically acceptable excipient, diluent, or carrier.

35. The compound of claim 1, wherein the compound is

36. The compound of claim 35, wherein the compound is

37. The compound of claim 36, wherein the compound is

38. The compound of claim 36, wherein the compound is

39. The compound of claim 1, wherein the compound is

40. The compound of claim 1, wherein the compound is

41. The compound of claim 1, wherein the compound is

42. The compound of claim 1, wherein the compound is

43. The compound of claim 1, wherein the compound is

44. The compound of claim 1, wherein the compound is

46. A pharmaceutical composition comprising a compound of claim 37, and a pharmaceutically acceptable excipient, diluent, or carrier.

47. A pharmaceutical composition comprising a compound of claim 38, and a pharmaceutically acceptable excipient, diluent, or carrier.

45. A compound of Formula (II):

48. The compound of claim 45, wherein the compound is