Claims for Patent: 10,695,323

Summary for Patent: 10,695,323

Title:	Compounds useful as kinase inhibitors
Abstract:	This invention relates to novel compounds. The compounds of the invention are tyrosine kinase inhibitors. Specifically, the compounds of the invention are useful as inhibitors of Bruton's tyrosine kinase (BTK). The invention also contemplates the use of the compounds for treating conditions treatable by the inhibition of Bruton's tyrosine kinase, for example cancer, lymphoma, leukemia and immunological diseases.
Inventor(s):	Guisot Nicolas
Assignee:	Loxo Oncology, Inc.
Application Number:	US16063542
Patent Claims:	2. The compound of claim 1 , wherein A is selected from the group consisting of: unsubstituted phenyl claim 1 , unsubstituted pyridine claim 1 , phenyl substituted by from 1 to 4 R claim 1 , and pyridine substituted by from 1 to 4 R.4. The compound of claim 1 , wherein Ris a group selected from a substituted: phenyl or 6 membered heteroaryl ring claim 1 , optionally wherein Ris substituted with 1 or 2 groups independently selected from: methyl claim 1 , fluoro claim 1 , or methoxy.5. The compound of claim 1 , wherein Ris 2-methoxyphen-1-yl or 5-fluoro-2-methoxyphen-1-yl.6. The compound of claim 1 , wherein Ris H.7. The compound of claim 1 , wherein Rand Rare independently selected at each occurrence from the group consisting of: H claim 1 , methyl claim 1 , ethyl claim 1 , cyclopropyl claim 1 , and —CHOH.8. The compound of claim 7 , wherein Rand Rare H.9. The compound of claim 1 , wherein m is 1.10. The compound of claim 1 , wherein m is 1 claim 1 , Rand Rare H claim 1 , Ris H claim 1 , Ris methoxyphenyl or methoxyfluorophenyl claim 1 , and A is unsubstituted phenyl or phenyl substituted by one or two R claim 1 , wherein when A is substituted Ris selected from: fluoro claim 1 , methyl claim 1 , methoxy claim 1 , or —CHOH.11. The compound of claim 1 , wherein Rrepresents a group selected from: halo claim 1 , Calkyl claim 1 , Chaloalkyl claim 1 , or —NRR claim 1 , wherein Rand Rare claim 1 , at each occurrence claim 1 , independently selected from the group consisting of: H and Calkyl.12. The compound of claim 1 , wherein Rrepresents —C(O)NH claim 1 , —C(O)NHMe claim 1 , —CHOH claim 1 , CH(OH)CH claim 1 , —CF claim 1 , or —CHF.14. The compound of claim 13 , wherein R claim 13 , R claim 13 , Rand Rare H.15. The compound of claim 1 , wherein Rrepresents a group selected from: Calkyl claim 1 , Chaloalkyl claim 1 , Calkyl ether claim 1 , —C(O)R claim 1 , Ccycloalkyl claim 1 , Caryl claim 1 , 3 to 10 membered heterocycloalkyl claim 1 , 3 to 10 membered heteroaryl claim 1 , Calkyl substituted with Ccycloalkyl claim 1 , Calkyl substituted with Caryl claim 1 , Calkyl substituted with 3 to 10 membered heterocycloalkyl claim 1 , or Calkyl substituted with 3 to 10 membered heteroaryl claim 1 , wherein each of the aforementioned groups are unsubstituted or substituted with 1 to 5 substituents selected from the group consisting of: halo claim 1 , Calkyl claim 1 , Chaloalkyl claim 1 , Calkoxy claim 1 , Calkyl ether claim 1 , —OR claim 1 , —CN claim 1 , ═O claim 1 , —C(O)OR claim 1 , —C(O)NRR claim 1 , 5 or 6 membered heteroaryl claim 1 , a 3 to 6 membered heterocycloalkyl ring claim 1 , Calkyl substituted with —OR claim 1 , and Calkoxy substituted with —OR claim 1 , or a single atom of Ris substituted twice so as to form a 3 to 6 membered heterocycloalkyl or cycloalkyl ring.16. The compound of claim 1 , wherein Ris selected from: H claim 1 , Calkyl claim 1 , Chaloalkyl claim 1 , benzyl claim 1 , or Calkyl substituted with —OR.17. The compound of claim 1 , wherein Ris selected from substituted or unsubstituted: methyl claim 1 , ethyl claim 1 , iso-propyl claim 1 , tert-hexyl claim 1 , tert-butyl claim 1 , trifluoroethyl claim 1 , propyl ether claim 1 , cyclopropyl claim 1 , cyclobutyl claim 1 , cyclopentyl claim 1 , cyclohexyl claim 1 , indanyl claim 1 , bicyclo[3.1.0]hexyl claim 1 , oxetane claim 1 , tetrahydropyranyl claim 1 , phenyl claim 1 , pyridyl claim 1 , Calkyl substituted with oxetane claim 1 , Calkyl substituted with morpholine claim 1 , Calkyl substituted with tetrazole claim 1 , Calkyl substituted with piperidine claim 1 , or Calkyl substituted with cyclohexyl claim 1 ,{'sup': '1', 'sub': 3', '2, 'wherein Ris substituted with 1 to 5 substituents selected from the group consisting of: —OH, ═O, —OMe, —CN, methyl, CF, Cl, F, —OBn, and —COEt.'}19. The compound of claim 18 , wherein Ris selected from methyl claim 18 , difluoromethyl or trifluoromethyl claim 18 , and Ris selected from methyl claim 18 , ethyl claim 18 , propyl claim 18 , trifluoromethyl claim 18 , difluoromethyl claim 18 , trifluorethyl claim 18 , —CHOH claim 18 , —CHCHOH claim 18 , —CHOMe claim 18 , pyrrolidinyl claim 18 , piperidinyl claim 18 , tetrahydrofuranyl claim 18 , tetrahydropyranyl claim 18 , pyridinyl claim 18 , phenyl claim 18 , cyclopropyl claim 18 , cyclobutyl claim 18 , cyclopentyl claim 18 , or cyclohexyl; provided that when Ris not methyl then Ris not methyl claim 18 , ethyl claim 18 , or propyl.20. The compound of claim 19 , wherein Ris trifluoromethyl.22. A pharmaceutical composition claim 1 , wherein the pharmaceutical composition comprises a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , and pharmaceutically acceptable excipients.23. The pharmaceutical composition of claim 22 , wherein the composition is a combination product and comprises an additional pharmaceutically active agent.24. A method of treatment of a condition which is modulated by BTK claim 1 , wherein the method comprises administering a therapeutic amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , to a patient in need thereof.25. The method of wherein the condition modulated by BTK is selected from the group consisting of: lymphoma claim 24 , leukemia claim 24 , autoimmune diseases claim 24 , an inflammatory disorder claim 24 , a heteroimmune condition claim 24 , and fibrosis.26. A method of treating a condition selected from the group consisting of: lymphoma claim 1 , leukemia claim 1 , an autoimmune disease claim 1 , an inflammatory disorder claim 1 , a heteroimmune condition claim 1 , and fibrosis claim 1 , wherein the method comprises administering a therapeutic amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , to a patient in need thereof.27. The method of claim 26 , wherein the condition is selected from the group consisting of: B-cell malignancy claim 26 , B-cell lymphoma claim 26 , diffuse large B cell lymphoma claim 26 , chronic lymphocyte leukemia claim 26 , non-Hodgkin lymphoma claim 26 , mantle cell lymphoma claim 26 , follicular lymphoma claim 26 , hairy cell leukemia claim 26 , B-cell non-Hodgkin lymphoma claim 26 , Waldenstrom's macroglobulinemia claim 26 , multiple myeloma claim 26 , bone cancer claim 26 , bone metastasis claim 26 , arthritis claim 26 , multiple sclerosis claim 26 , osteoporosis claim 26 , irritable bowel syndrome claim 26 , inflammatory bowel disease claim 26 , Crohn's disease claim 26 , lupus claim 26 , Sjögren's syndrome claim 26 , and a disorder associated with renal transplant.28. A method of treatment of a condition selected from the group consisting of: lymphoma claim 1 , leukemia claim 1 , an autoimmune disease claim 1 , an inflammatory disorder claim 1 , a heteroimmune condition claim 1 , and fibrosis comprising administering a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof claim 1 , simultaneously claim 1 , sequentially or separately with an additional anti-tumour agent to a patient in need thereof.29. A method of claim 28 , wherein the condition is selected from the group consisting of: B-cell malignancy claim 28 , B-cell lymphoma claim 28 , diffuse large B cell lymphoma claim 28 , chronic lymphocyte leukemia claim 28 , non-Hodgkin lymphoma claim 28 , mantle cell lymphoma claim 28 , follicular lymphoma claim 28 , hairy cell leukemia claim 28 , B-cell non-Hodgkin lymphoma claim 28 , Waldenstrom's macroglobulinemia claim 28 , multiple myeloma claim 28 , bone cancer claim 28 , bone metastasis claim 28 , arthritis claim 28 , multiple sclerosis claim 28 , osteoporosis claim 28 , irritable bowel syndrome claim 28 , inflammatory bowel disease claim 28 , Crohn's disease claim 28 , lupus claim 28 , Sjögren's syndrome claim 28 , and a disorder associated with renal transplant.33. The method of wherein the condition is selected from the group consisting of: B-cell malignancy claim 31 , B-cell lymphoma claim 31 , diffuse large B cell lymphoma claim 31 , chronic lymphocyte leukemia claim 31 , non-Hodgkin lymphoma claim 31 , mantle cell lymphoma claim 31 , follicular lymphoma claim 31 , hairy cell leukemia claim 31 , B-cell non-Hodgkin lymphoma claim 31 , Waldenstrom's macroglobulinemia claim 31 , multiple myeloma claim 31 , bone cancer claim 31 , bone metastasis claim 31 , arthritis claim 31 , multiple sclerosis claim 31 , osteoporosis claim 31 , irritable bowel syndrome claim 31 , inflammatory bowel disease claim 31 , Crohn's disease claim 31 , lupus claim 31 , Sjögren's syndrome claim 31 , and a disorder associated with renal transplant.34. The method of wherein the condition is selected from the group consisting of: B-cell malignancy claim 32 , B-cell lymphoma claim 32 , diffuse large B cell lymphoma claim 32 , chronic lymphocyte leukemia claim 32 , non-Hodgkin lymphoma claim 32 , mantle cell lymphoma claim 32 , follicular lymphoma claim 32 , hairy cell leukemia claim 32 , B-cell non-Hodgkin lymphoma claim 32 , Waldenstrom's macroglobulinemia claim 32 , multiple myeloma claim 32 , bone cancer claim 32 , bone metastasis claim 32 , arthritis claim 32 , multiple sclerosis claim 32 , osteoporosis claim 32 , irritable bowel syndrome claim 32 , inflammatory bowel disease claim 32 , Crohn's disease claim 32 , lupus claim 32 , Sjögren's syndrome claim 32 , and a disorder associated with renal transplant.35. The method of wherein the condition is selected from the group consisting of: B-cell malignancy claim 34 , B-cell lymphoma claim 34 , diffuse large B cell lymphoma claim 34 , chronic lymphocyte leukemia claim 34 , non-Hodgkin lymphoma claim 34 , and mantle cell lymphoma.