Claims for Patent: 7,989,477

Summary for Patent: 7,989,477

Title:	Monocyclic heterocycles as kinase inhibitors
Abstract:	The present invention is directed to compounds having the formula ##STR00001## and methods for using them for the treatment of cancer.
Inventor(s):	Borzilleri; Robert M. (New Hope, PA), Cornelius; Lyndon A. M. (Jackson, NJ), Schmidt; Robert J. (Hainesport, NJ), Schroeder; Gretchen M. (Ewing, NJ), Kim; Kyoung S. (North Brunswick, NJ)
Assignee:	Bristol-Myers Squibb Company (Princeton, NJ)
Application Number:	12/727,534
Patent Claims:	1. A method for treating cancer in a patient in need thereof, wherein the cancer overexpresses MET receptor, wherein said cancer is colon cancer, kidney cancer, lung cancer, pancreatic cancer or stomach cancer, comprising administering to the patient a therapeutically effective amount of a compound having Formula II: ##STR00424## or an enantiomer, diastereomer, or pharmaceutically acceptable salt thereof wherein: each R.sup.2 is independently H, halogen, OR.sup.5, NR.sup.6R.sup.7, alkyl, and/or haloalkyl; B is O, S, SO, or SO.sub.2; W is C; X is C; n is zero to 4; R.sup.3, R.sup.5, R.sup.6, and R.sup.7 are independently H and/or alkyl; R.sup.4 is pyridinone or pyridyl-N-oxide substituted with phenyl, fluorophenyl or benzyl; A is ##STR00425## R.sup.16, R.sup.17, R.sup.18, and R.sup.19 are H, halogen, NR.sup.30R.sup.31, OR.sup.32, alkyl, hydroxyalkyl, pyridyl, alkenyl, alkynyl, and/or alkynyl substituted with --OH, --NH.sub.2, --N(alkyl).sub.2, or pyridyl, phenyl, phenyl substituted with aminoalkyl; R.sup.30 and R.sup.31 are independently H, alkyl, aminoalkyl, benzyl, methoxybenzyl, phenyl, fluorophenyl, and pyridyl; and R.sup.32 is H or alkyl. 2. The method according to claim 1, wherein B is O. 3. The method according to claim 2, wherein: R.sup.2 is H or halogen; and R.sup.3 is H. 4. The method according to claim 2, wherein R.sup.4 is pyridinonyl substituted with one substituent selected from phenyl, fluorophenyl, and benzyl. 5. The method according to claim 4, wherein: R.sup.18 and R.sup.19 are each H. 6. The method according to claim 2, wherein R.sup.4 is optionally substituted pyridyl-N-oxide substituted with one substituent phenyl, fluorophenyl, and benzyl. 7. The method according to claim 6, wherein: R.sup.18 and R.sup.19 are each H. 8. A method for treating cancer in a patient in need thereof, wherein the cancer overexpresses MET receptor, wherein said cancer is colon cancer, kidney cancer, lung cancer, pancreatic cancer or stomach cancer, comprising administering to the patient a therapeutically effective amount of a compound selected from: N-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl)-5-benzyl-4-oxo-1,4-dihydrop- yridine-3-carboxamide, trifluoroacetic acid salt (56); N-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl)-2-oxo-1-phenyl-1,2-dihydrop- yridine-3-carboxamide, trifluoroacetic acid salt (57); N-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl)-6-(4-fluorophenyl)pyridyl-N- -oxide-amide, trifluoroacetic acid salt (58); N-(3-Fluoro-4-(3-(6-(piperazin-1-yl)pyridin-3-yl)pyridin-4-yloxy)phenyl)-- 2-oxo-1-phenyl-1,2-dihydropyridine-3-carboxamide, hydrochloride salt (62); N-(3-Fluoro-4-(3-(4-(piperazin-1-yl)phenyl)pyridin-4-yloxy)phenyl)-2-oxo-- 1-phenyl-1,2-dihydropyridine-3-carboxamide, trihydrochloride salt (66); N-(3-Fluoro-4-(3-(4-(2-hydroxyethyl)phenyl)pyridin-4-yloxy)phenyl)-2-oxo-- 1-phenyl-1,2-dihydropyridine-3-carboxamide (67); N-(4-(3-(4-(2-Aminoethyl)phenyl)pyridin-4-yloxy)-3-fluorophenyl)-2-oxo-1-- phenyl-1,2-dihydropyridine-3-carboxamide, dihydrochloride salt (68); N-(4-(3-(4-((2-(methylamino)ethyl)carbamoyl)phenyl)pyridin-4-yloxy)-3-flu- orophenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide, dihydrochloride salt (69); N-(4-(3-(4-((2-aminoethyl)carbamoyl)phenyl)pyridin-4-yloxy)-3-fluoropheny- l)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide, dihydrochloride salt (70); N-(4-(3-(4-((2-(dimethylamino)ethyl)carbamoyl)phenyl)pyridin-4-yloxy)-3-f- luorophenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide, dihydrochloride salt (71); N-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl)-1-(4-fluorophenyl)-2-oxo-1,- 2-dihydropyridine-3-carboxamide, hydrochloride salt (101); N-(4-(2-Amino-3-(4-(2-amino-2-oxoethyl)phenyl)pyridin-4-yloxy)-3-fluoroph- enyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide, hydrochloride salt (111); N-(4-(2-Aminopyridin-4-yloxy)-2,5-difluorophenyl)-2-oxo-1-phenyl-1,2-dihy- dropyridine-3-carboxamide, hydrochloric acid salt (114); N-(4-(2-Aminopyridin-4-yloxy)-2,5-difluorophenyl)-1-(4-fluorophenyl)-2-ox- o-1,2-dihydropyridine-3-carboxamide, hydrochloric acid salt (115); N-(4-(3-Aminopyridin-4-yloxy)-3-fluorophenyl)-1-(4-fluorophenyl)-2-oxo-1,- 2-dihydropyridine-3-carboxamide (120); N-(3-Fluoro-4-(3-(pyrrolidin-3-ylmethylamino)pyridin-4-yloxy)phenyl)-1-(4- -fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide, hydrochloride salt (121); N-(4-(3-(2-Aminoethylamino)pyridin-4-yloxy)-3-fluorophenyl)-1-(4-f- luorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide, hydrochloride salt (122); N-(3-Fluoro-4-(3-(piperidin-2-ylmethylamino)pyridin-4-yloxy)phenyl- )-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide, hydrochloride salt (123); N-(4-(3-(3-(Dimethylamino)-2,2-dimethylpropylamino)pyridin-4-yloxy)-3-flu- orophenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide, hydrochloride salt (124); N-(4-(3-(2-Amino-3-hydroxypropylamino)pyridin-4-yloxy)-3-fluorophenyl)-1-- (4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide, hydrochloride salt (125); N-(4-(2-Amino-3-((2-aminoethylamino)methyl)pyridin-4-yloxy)-3-fluoropheny- l)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide, trifluoroacetic acid salt (129); N-(4-(2-amino-3-(hydroxymethyl)pyridin-4-yloxy)-3-fluorophenyl)-1-(4-fluo- rophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide, trifluoroacetic acid salt (130); N-(4-(2-Amino-3-(4-(2-amino-2-oxoethyl)phenyl)pyridin-4-yloxy)-3-fluoroph- enyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide, hydrochloride salt (132); N-(4-(2-Amino-3-(3-((3R,4R)-3-hydroxy-4-(pyrrolidin-1-yl)pyrrolidin-1-yl)- -3-methylbut-1-ynyl)pyridin-4-yloxy)-3-fluorophenyl)-1-(4-fluorophenyl)-2-- oxo-1,2-dihydropyridine-3-carboxamide, trihydrochloride salt (134); N-(4-(2-Amino-3-(3-aminoprop-1-ynyl)pyridin-4-yloxy)-3-fluorophenyl)-1-(4- -fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide, dihydrochloride salt (137); N-(4-(2-Amino-3-(3-(dimethylamino)prop-1-ynyl)pyridin-4-yloxy)-3-fluoroph- enyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide, dihydrochloride salt (140); N-(4-(2-Aminopyridin-4-yloxy)phenyl)-2-oxo-1-phenyl-1,2-dihydropyridine-3- -carboxamide, hydrochloride salt (146); and N-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl)-1-benzyl-2-oxo-1,2-dihydrop- yridine-3-carboxamide, hydrochloride salt (147). 9. The method according to claim 1, further comprising administering at least one other anticancer agent, wherein said other anticancer agent is selected from gefitinib, erlotinib, and cetuximab. 10. The method according to claim 1, wherein said cancer is kidney cancer. 11. The method according to claim 1, wherein said cancer is lung cancer. 12. The method according to claim 1, wherein said cancer is pancreatic cancer.

Details for Patent 7,989,477

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	02/12/2004		2024-04-23
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	03/28/2007		2024-04-23