Claims for Patent: 9,255,108

Summary for Patent: 9,255,108

Title:	Heterocyclic compounds and uses thereof
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.
Inventor(s):	Castro; Alfredo C. (Woburn, MA), Chan; Katrina (Fremont, CA), Evans; Catherine A. (Somerville, MA), Janardanannair; Somarajannair (Woburn, MA), Lescarbeau; Andre (Somerville, MA), Li; Liansheng (San Diego, CA), Liu; Tao (Ashland, MA), Liu; Yi (San Diego, CA), Ren; Pingda (San Diego, CA), Snyder; Daniel A. (Somerville, MA), Tremblay; Martin R. (Melrose, MA)
Assignee:	Infinity Pharmaceuticals, Inc. (Cambridge, MA)
Application Number:	14/573,961
Patent 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): ##STR00793## or an enantiomer, a mixture of enantiomers, or a mixture of two or more diastereomers thereof, or a pharmaceutically acceptable form thereof, wherein Cy is 6-membered aryl substituted by 1 occurrence of R.sup.3 and 0, 1, 2, or 3 occurrence(s) of R.sup.5; W.sub.b.sup.5 is CR.sup.8 or CHR.sup.8; R.sup.8 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heteroalkyl, alkoxy, amido, amino, acyl, acyloxy, sulfonamido, halo, cyano, hydroxyl or nitro; B is hydrogen, alkyl, amino, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is substituted with 0, 1, 2, 3, or 4 occurrence(s) of R.sup.2; each R.sup.2 is independently alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkoxy, amido, amino, acyl, acyloxy, alkoxycarbonyl, sulfonamido, halo, cyano, hydroxyl, nitro, phosphate, urea, or carbonate; X is --(CH(R.sup.9)).sub.z--; Y is --NH--C(.dbd.O)--, --C(.dbd.O)--N(R.sup.9)--, or --C(.dbd.O)--N(R.sup.9)--(CHR.sup.9)--; z is an integer of 1, 2, 3, or 4; R.sup.3 is alkyl, cycloalkyl, heterocyclyl, fluoroalkyl, heteroalkyl, alkoxy, amido, amino, acyl, acyloxy, sulfinyl, sulfonyl, sulfoxide, sulfone, sulfonamido, halo, cyano, aryl, heteroaryl, hydroxyl, or nitro; each R.sup.5 is independently alkyl, cycloalkyl, heteroalkyl, alkoxy, amido, amino, acyl, acyloxy, sulfonamido, halo, cyano, hydroxyl, or nitro; each R.sup.9 is independently hydrogen, alkyl, cycloalkyl, heterocyclyl, or heteroalkyl; or two adjacent occurrences of R.sup.9 together with the atoms to which they are attached form a 4- to 7-membered ring; W.sub.d is ##STR00794## ##STR00795## X.sub.1, X.sub.2 and X.sub.3 are each independently C, CR.sup.13, or N; X.sub.4, X.sub.5 and X.sub.6 are each independently N, NH, CR.sup.13, S, or O; and wherein R.sup.10, R.sup.11, R.sup.12, and R.sup.13 are each independently hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkoxy, heterocyclyloxy, amido, amino, acyl, acyloxy, alkoxycarbonyl, sulfonamido, halo, cyano, hydroxyl, nitro, phosphate, urea, carbonate, or NR'R'' wherein R' and R'' are taken together with nitrogen to form a cyclic moiety; wherein the inflammatory disease or auto-immune disease is selected from asthma, emphysema, dermatitis, rheumatoid arthritis, psoriasis, lupus erythematosus, graft versus host disease, inflammatory bowel disease, eczema, scleroderma, multiple sclerosis, and chronic obstructive pulmonary disease. 2. The method of claim 1, wherein the compound of Formula (I) is a compound of Formula (IIIb): ##STR00796## wherein R.sup.8 is hydrogen, alkyl, cyano, or halo; R.sup.9 is hydrogen or alkyl, and Y is --NH--C(O)--. 3. The method of claim 1, wherein the compound of Formula (I) is a compound of Formula (II): ##STR00797## 4. The method of claim 1, wherein R.sup.3 is halo, cyano, hydroxy, alkyl, alkoxy, amino, acyl, heteroaryl, aryl, heterocyclyl, or cycloalkyl. 5. The method of claim 4, wherein R.sup.3 is heteroaryl, aryl, alkyl, haloalkyl, OH, Cl, or F. 6. The method of claim 5, wherein R.sup.3 is heteroaryl, phenyl, CH.sub.3, CF.sub.3, OH, or Cl. 7. The method of claim 1, wherein R.sup.8 is H, CH.sub.3, OCH.sub.3, CF.sub.3, 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 R.sup.2. 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 R.sup.2. 11. The method of claim 10, wherein R.sup.2 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.sub.d is: ##STR00798## wherein one of X.sub.1 and X.sub.2 is N and one of X.sub.1 and X.sub.2 is C or CR.sup.13; and X.sub.3 is CR.sup.13 or N. 14. The method of claim 1, wherein W.sub.d is: ##STR00799## 15. The method of claim 1, wherein W.sub.d is: ##STR00800## 16. The method of claim 1, wherein W.sub.d is: ##STR00801## 17. The method of claim 1, wherein W.sub.d is ##STR00802## 18. The method of claim 13, wherein R.sup.10 is NH.sub.2. 19. The method of claim 1, wherein X is --CH(CH.sub.3)--. 20. The method of claim 19, wherein the CH carbon of the --CH(CH.sub.3)-- 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 --CH.sub.2--N(CH.sub.3)--C(O)--. 23. The method of claim 1, wherein --X--Y-- is (S)--CH(CH.sub.3)--NH--C(O)--. 24. The method of claim 1, wherein the compound is ##STR00803## ##STR00804## ##STR00805## ##STR00806## ##STR00807## ##STR00808## ##STR00809## or a pharmaceutically acceptable form thereof. 25. The method of claim 1, wherein the compound is ##STR00810## or a pharmaceutically acceptable form thereof. 26. The method of claim 1, wherein the compound is ##STR00811## or a pharmaceutically acceptable form thereof. 27. The method of claim 1, wherein the compound is ##STR00812## or a pharmaceutically acceptable form thereof. 28. The method of claim 1, wherein the compound is ##STR00813## ##STR00814## ##STR00815## ##STR00816## ##STR00817## ##STR00818## ##STR00819## ##STR00820## ##STR00821## ##STR00822## ##STR00823## or a pharmaceutically acceptable form thereof. 29. The method of claim 1, wherein the compound is ##STR00824## ##STR00825## ##STR00826## ##STR00827## ##STR00828## ##STR00829## ##STR00830## ##STR00831## ##STR00832## ##STR00833## ##STR00834## ##STR00835## ##STR00836## ##STR00837## ##STR00838## ##STR00839## ##STR00840## ##STR00841## ##STR00842## ##STR00843## ##STR00844## ##STR00845## ##STR00846## ##STR00847## ##STR00848## ##STR00849## ##STR00850## ##STR00851## or a pharmaceutically acceptable form 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): ##STR00852## or an enantiomer, a mixture of enantiomers, or a mixture of two or more diastereomers thereof, or a pharmaceutically acceptable form thereof, wherein R.sup.8 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heteroalkyl, alkoxy, amido, amino, acyl, acyloxy, sulfonamido, halo, cyano, hydroxyl or nitro; B is hydrogen, alkyl, amino, heteroalkyl, cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is substituted with 0, 1, 2, 3, or 4 occurrence(s) of R.sup.2; each R.sup.2 is independently alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkoxy, amido, amino, acyl, acyloxy, alkoxycarbonyl, sulfonamido, halo, cyano, hydroxyl, nitro, phosphate, urea, or carbonate; X is --(CH(R.sup.9)).sub.z--; Y is --N(R.sup.9)--C(.dbd.O)--, --C(.dbd.O)--N(R.sup.9)--, or --C(.dbd.O)--N(R.sup.9)--(CHR.sup.9)--; z is an integer of 1, 2, 3, or 4; R.sup.3 is alkyl, cycloalkyl, heterocyclyl, fluoroalkyl, heteroalkyl, alkoxy, amido, amino, acyl, acyloxy, sulfinyl, sulfonyl, sulfoxide, sulfone, sulfonamido, halo, cyano, aryl, heteroaryl, hydroxyl, or nitro; each R.sup.9 is independently hydrogen, alkyl, cycloalkyl, heterocyclyl, or heteroalkyl; or two adjacent occurrences of R.sup.9 together with the atoms to which they are attached form a 4- to 7-membered ring; W.sub.d is ##STR00853## ##STR00854## X.sub.1, X.sub.2 and X.sub.3 are each independently C, CR.sup.13, or N; X.sub.4, X.sub.5 and X.sub.6 are each independently N, NH, CR.sup.13, S, or O; and wherein R.sup.10, R.sup.11, R.sup.12, and R.sup.13 are each independently hydrogen, alkyl, heteroalkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, alkoxy, heterocyclyloxy, amido, amino, acyl, acyloxy, alkoxycarbonyl, sulfonamido, halo, cyano, hydroxyl, nitro, phosphate, urea, carbonate, or NR'R'' wherein R' and R'' are taken together with nitrogen to form a cyclic moiety; wherein the inflammatory disease or auto-immune disease is selected from asthma, emphysema, dermatitis, rheumatoid arthritis, psoriasis, lupus erythematosus, graft versus host disease, inflammatory bowel disease, eczema, scleroderma, multiple sclerosis, and chronic obstructive pulmonary disease. 31. The method of claim 30, wherein the compound is ##STR00855## or a pharmaceutically acceptable form thereof. 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.

Details for Patent 9,255,108

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Genentech, Inc.	RITUXAN	rituximab	Injection	103705	11/26/1997		2032-04-10
Idec Pharmaceuticals Corp.	RITUXAN	rituximab	Injection	103737	02/19/2002		2032-04-10
Genentech, Inc.	RITUXAN HYCELA	rituximab and hyaluronidase human	Injection	761064	06/22/2017		2032-04-10