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US 7,459,562 B2Granted
Monocyclic heterocycles as kinase inhibitors
AssigneeBristol-Myers Squibb Company
InventorsRobert M. Borzilleri, Lyndon A. M. Cornelius, Robert J. Schmidt, Gretchen M. Schroeder, Kyoung S. Kim
Life of this patent
Estimating the term…
Abstract
The present invention is directed to compounds having the formula and methods for using them for the treatment of cancer.
Claims17
A compound having Formula II:
- or an enantiomer, diastereomer, or pharmaceutically acceptable salt thereof wherein:
- each R2 is independently H, halogen, OR5, NR6R7, alkyl, and/or haloalkyl;
- B is O, S, SO, or SO2;
- W is C;
- X is C;
- n is zero to 4;
- R3, R5, R6, and R7 are independently H and/or alkyl;
- R4 is a monocyclic 5- to 6-membered nitrogen containing heteroaryl, optionally substituted with one or more substituents selected from alkyl, hydroxy, alkoxy, halogen, phenyl, fluorophenyl, ═O, and benzyl, provided that
- (a) if R4 is monocyclic ring pyridyl, R4 is monocyclic ring not substituted with both hydroxy and methoxy;
- and
- (b) if R4 is monocyclic ring pyrimidinyl, it is not substituted with ═O;
- R16, R17, R18, and R19 are H, halogen, NR30R31, OR32, alkyl, hydroxyalkyl, pyridyl, alkenyl, alkynyl, and/or alkynyl substituted with —OH, —NH2, —N(alkyl)2, or pyridyl, phenyl, phenyl substituted with aminoalkyl;
- R30 and R31 are independently selected from H, alkyl, aminoalkyl, benzyl, methoxybenzyl, phenyl, fluorophenyl, and pyridyl;
- and
- R32 is H or alkyl.
12 more elements
A compound selected from:
- N-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl)-2-bromoisonicotinamide, trifluoroacetic acid salt (48);
- N-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl)-2-(4-fluorophenylamino) isonicotinamide, bis-trifluoroacetic acid salt (49);
- N-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl)-6-oxo-1,6-dihydropyridine-2-carboxamide, trifluoroacetic acid salt (50);
- N-(4-(2-aminopyridin-4-yloxy)-3-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide, trifluoroacetic acid salt (51);
- N-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl)-6-methyl-2-oxo-1,2-dihydropyridine-3-carboxamide, trifluroacetic acid salt (52);
- N-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl)-5-chloro-2-oxo-1,2-dihydropyridine-3-carboxamide, trifluoroacetic acid salt (53);
- N-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl)-5-bromo-2-oxo-1,2-dihydropyridine-3-carboxamide, trifluoroacetic acid salt (54);
- N-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl)-6-methyl-4-oxo-1,4-dihydropyridine-3-carboxamide, trifluoroacetic acid salt (55);
- N-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl)-5-benzyl-4-oxo-1,4-dihydropyridine-3-carboxamide, trifluoroacetic acid salt (56);
- N-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl)-2-oxo-1-phenyl-1,2-dihydropyridine-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-fluorophenyl)-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-fluorophenyl)-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-fluorophenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide, dihydrochloride salt (71);
- N-(4-(2-Aminopyridin-4-yloxy)-3-fluorophenyl)-1-benzyl-5-methyl-1H-pyrazole-3-carboxamide, hydrochloride salt (98);
- 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-fluorophenyl)-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-dihydropyridine-3-carboxamide, hydrochloric acid salt (114);
- N-(4-(2-Aminopyridin-4-yloxy)-2,5-difluorophenyl)-1-(4-fluorophenyl)-2-oxo-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-fluorophenyl)-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-fluorophenyl)-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-fluorophenyl)-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-fluorophenyl)-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-fluorophenyl)-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-fluorophenyl)-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-dihydropyridine-3-carboxamide, hydrochloride salt (147).
34 more elements
Dependencies are inferred from the claim text.