US 2007/0185092 A1Published application

FACTOR Xa INHIBITORS

AssigneeMillennium Pharmaceuticals, Inc.

InventorsBing-Yan Zhu, Shawn Bauer, Zhaozhong Jia, Yonghong Song, Gary Probst, Yanchen Zhang, Robert Scarborough

Life of this patent

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Abstract

The present invention is directed to compounds represented by Formula (I) or a pharmaceutically acceptable salt, ester, or prodrug thereof which are inhibitors of Factor Xa. The present invention is also directed to and intermediates used in making such compounds, pharmaceutical compositions containing such compounds, methods to prevent or treat a number of conditions characterized by undesired thrombosis and methods of inhibiting the coagulation of a blood sample.

Claims19

Dependent claims

A compound of Formula (I) or a pharmaceutically acceptable salt, ester, or prodrug thereof

wherein:
R1 is selected from the group consisting of halogen, C1-8 alkyl, C2-8 alkenyl, and C2-8 alkynyl;
R2 is hydrogen or C1-4 alkyl;
A is selected from the group consisting of:
wherein the wavy line indicates the point of attachment ring B and the dashed line indicates the point of attachment to the rest of the molecule;
R3 is independently hydrogen or R3a;
R3a is independently selected from the group consisting of halogen, C1-8 alkyl, C2-8 alkenyl, and C2-8 alkynyl;
m is 0, 1, 2, or 3;
X is C—R4 or N or X and Y are C and are fused to a 6-membered aryl, heteroaryl, or heterocyclic ring;
Y is C—R5 or N provided that X and Y are not both N;
R4 is selected from the group consisting of hydrogen, halogen, and
R4a is hydrogen or C1-8 alkyl;
R5 is selected from the group consisting of hydrogen, halogen, and C1-8 alkoxy;
or R5 and R6 together join to form a 6-membered aryl, heteroaryl, or heterocyclic ring fused to ring B;
R6 is selected from the group consisting of —R6a, —NR7aR7b, —NR7aC(O)R7c, —NR7aC(O)OR7c, —CONR8aR8b, —OR7c, —SR7c, —C(═NR7a)NR8aR8b, —S(O)2NR8aR8b, and —S(O)2R7c;
R6a is selected from the group consisting of
wherein R8 can be at any position suitable for a substituent, and if R8 is attached to a nitrogen atom, then it replaces the hydrogen atom attached thereto;
R7a and R7b are independently selected from the group consisting of hydrogen, C1-8 alkyl, and C1-8 alkyl substituted with one to three R9;
R7c is selected from the group consisting of aryl, heteroaryl, C1-8 alkyl, and C1-8 alkyl substituted with one to three R9;
R8 is independently selected from the group consisting of nitro, hydroxy, —CO2H, —C(O)R8c, —C(O)NR8aR8b, —NR8aR8b, —SO2NR8aR8b, halogen, C1-8 alkyl, and C1-8 alkoxy wherein said C1-8 alkyl and C1-8 alkoxy are optionally substituted with one to three R9;
R8a and R8b are independently selected from the group consisting of hydrogen, C1-8 alkyl, and C1-8 alkyl substituted with one to three R9, or R8a and R8b together form a 5 to 7 membered heterocyclic ring optionally substituted with one to three R9 and optionally having one additional ring heteroatom selected from N, O, or S;
R8c is selected from the group consisting of C1-8 alkyl and C1-8 alkyl substituted with one to three R9;
R9 is independently selected from the group consisting of halogen, heterocyclic, heteroaryl, —OH, —R10, —OR10, —SR10, —S(O)R10, —S(O)2R10, —SO2NH2, —C(O)NH2, —C(O)R10, —C(NH)R10, —NHC(O)R10, —NHC(NH)R10, —NHC(O)NH2, —CO2H, —NH2, —NHR10, —N(R10)2 and —N(R10)3+;
each R10 is independently C1-6 alkyl;
and
n is 0, 1, 2, or 3;
provided that when X is C—R4, Y is C—R5, R6 is R6a, and A is
then R6a is bound to ring B through a carbon atom.

25 more elements

A compound selected from the group consisting of:

5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(piperazin-1-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(4-ethylpiperazin-1-yl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(4-isopropylpiperazin-1-yl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyrimidin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2,4-dimethoxypyrimidin-5-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-((dimethylamino)methyl)-1H-imidazol-1-yl)-2-fluorophenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-methyl-1H-imidazol-1-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(4-methyl-1,4-diazepan-1-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxoimidazolidin-1-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2′-methoxybiphenyl-4-yl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2′-hydroxybiphenyl-4-yl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2′-(trifluoromethoxy)biphenyl-4-yl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(6-chloropyridin-3-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
N-((1-(4-(1H-Indol-2-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
5-Chloro-N-((1-(4-(methylsulfonyl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(3-fluoro-2′-sulfamoylbiphenyl-4-yl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(pyrrolidine-1-carbonyl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2,5-dihydro-1H-pyrrole-1-carbonyl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
N-((1-(4-Carbamoylphenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
N-((1-(4-(2-Amino-N-methylacetamido)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
5-Chloro-N-((1-(4-(methyl(2-(methylamino)ethyl)amino)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(methylamino)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(N-methylpropionamido)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
Ethyl 4-(4-((5-chlorothiophene-2-carboxamido)methyl)-1H-1,2,3-triazol-1-yl)phenyl(methyl)carbamate,
5-Chloro-N-((1-(4-(2-methoxy-N-methylacetamido)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-(dimethylamino)-N-methylacetamido)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(N-methylacetamido)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-hydroxyethoxy)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(6-oxo-1,6-dihydropyridazin-3-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((3-(2-fluoro-4-(2-oxopyridin-1(2H)-yl)phenyl)-5-methyl-4,5-dihydroisoxazol-5-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((5-oxo-1-(4-(2-oxopyridin-1(2H)-yl)phenyl)-4,5-dihydro-1H-pyrazol-3-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((2-oxo-1-(4-(2-oxopyridin-1(2H)-yl)phenyl)-1,2-dihydropyridin-3-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((6-oxo-1-(4-(2-oxopyridin-1(2H)-yl)phenyl)-1,6-dihydropyridin-3-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-methyl-2-(4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-imidazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-iodophenyl)-1H-imidazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)phenyl)-1H-imidazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-methoxypyridin-3-yl)phenyl)-1H-imidazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxo-1,2-dihydropyridin-3-yl)phenyl)-1H-imidazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(1-methyl-2-oxo-1,2-dihydropyridin-3-yl)phenyl)-1H-imidazol-4-yl)methyl)thiophene-2-carboxamide,
N-((1-(4-Aminophenyl)-1H-imidazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2,5-dihydro-1H-pyrrole-1-carbonyl)phenyl)-1H-imidazol-4-yl)methyl)thiophene-2-carboxamide,
4-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-imidazol-4-yl)methyl)benzamide,
N-((1-(4-(2-Oxopyridin-1(2H)-yl)phenyl)-1H-imidazol-4-yl)methyl)acetamide,
5-Chloro-N-((1-(5-(2-oxopyridin-1(2H)-yl)pyridin-2-yl)-1H-imidazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(6-(2-oxopyridin-1(2H)-yl)pyridin-3-yl)-1H-imidazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((2,5-dibromo-1-(4-(N,N-dimethylcarbamimidoyl)phenyl)-1H-imidazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((2,5-dibromo-1-(4-(imino(pyrrolidin-1-yl)methyl)phenyl)-1H-imidazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((2,5-dibromo-1-(4-(1-methyl-4,5-dihydro-1H-imidazol-2-yl)phenyl)-1H-imidazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(9-methyl-2,6-dioxo-1H-purin-3 (2H,6H,9H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)phenyl)-1H-imidazol-5-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((4-methyl-1-(4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-imidazol-5-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyrazin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-fluoro-4-(2-oxopyrazin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-fluoro-4-(2-oxopyrimidin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxotetrahydropyrimidin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-fluoro-4-(2-oxo-tetrahydropyrimidin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-fluoro-4-(3-methyl-2-oxo-tetrahydropyrimidin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-fluoro-4-(2-oxopiperidin-1-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(3-fluoro-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(3-hydroxy-2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(3-(2-hydroxyethoxy)-2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(3-(2-methoxyethoxy)-2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(3-(2-(dimethylamino)ethoxy)-2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(3-(2-(dimethyl(dimethylamino)amino)ethoxy)-2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxo-3-(2-(piperidin-1-yl)ethoxy)pyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxo-3-(3-(piperidin-1-yl)propoxy)pyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(3-(2-(methylthio)ethoxy)-2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(3-(2-(methylsulfinyl)ethoxy)-2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(3-(2-(methylsulfonyl)ethoxy)-2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(3-(2-morpholinoethoxy)-2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
N-((1-(4-(3-(2-(1H-Imidazol-1-yl)ethoxy)-2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
5-Chloro-N-((1-(4-(3-((1-methyl-1H-imidazol-2-yl)methoxy)-2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(5-hydroxy-2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(5-(2-(dimethylamino)ethoxy)-2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxo-5-(2-(piperidin-1-yl)ethoxy)pyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(5-(2-morpholinoethoxy)-2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(5-nitro-2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
N-((1-(4-(4-Amino-2-oxopyrimidin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
N-((1-(4-(4-Amino-5-fluoro-2-oxopyrimidin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
5-Chloro-N-((1-(4-(3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopiperazin-1-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(4-methyl-2-oxopiperazin-1-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(4-isopropyl-2-oxopiperazin-1-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
4-(4-(4-((5-Chlorothiophene-2-carboxamido)methyl)-1H-1,2,3-triazol-1-yl)phenyl)-3-oxopiperazine-1-carboxamide,
5-Chloro-N-((1-(4-(3-hydroxy-2-oxopyrazin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(4-(2-(dimethylamino)ethyl)-2,3-dioxo-3,4-dihydropyrazin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(3-hydroxy-6-oxopyridazin-1(6H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
2-((1-(4-(2-Oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methylcarbamoyl)benzoic acid,
N-((1-(2-(3-Oxopiperazin-1-yl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(1-methyl-4,5-dihydro-1H-imidazol-2-yl)phenyl)-1H-1,2,3-triazol-5-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(N,N-dimethylcarbamimidoyl)phenyl)-1H-1,2,3-triazol-5-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(imino(pyrrolidin-1-yl)methyl)phenyl)-1H-1,2,3-triazol-5-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(imino(piperidin-1-yl)methyl)phenyl)-1H-1,2,3-triazol-5-yl)methyl)thiophene-2-carboxamide,
N-((1-(4-Carbamoylphenyl)-1H-1,2,3-triazol-5-yl)methyl)-5-chlorothiophene-2-carboxamide,
5-Chloro-N-((1-(4-(methylsulfonyl)phenyl)-1H-1,2,3-triazol-5-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-5-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(pyridin-2-ylthio)phenyl)-1H-1,2,3-triazol-5-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(6-(pyrrolidin-1-yl)pyridin-3-yl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
1-(5-(4-((5-Chlorothiophene-2-carboxamido)methyl)-1H-1,2,3-triazol-1-yl)pyridin-2-yl)piperidine-4-carboxylic acid,
N-((1-(6-(Azepan-1-yl)pyridin-3-yl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
5-Chloro-N-((1-(6-(4-methyl-1,4-diazepan-1-yl)pyridin-3-yl)-1H-1,2,3-triazol-5-yl)methyl)thiophene-2-carboxamide,
N-((1-(6-(1,4-Diazepan-1-yl)pyridin-3-yl)-1H-1,2,3-triazol-5-yl)methyl)-5-chlorothiophene-2-carboxamide,
5-Chloro-N-((1-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-1,2,3-triazol-5-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(6-(piperazin-1-yl)pyridin-3-yl)-1H-1,2,3-triazol-5-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-(4-(4-((5-chlorothiophene-2-carboxamido)methyl)-1H-imidazol-1-yl)benzyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-pyrrol-3-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-pyrazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(4-methyl-1,4-diazepan-1-yl)phenyl)-1H-pyrazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyrazin-1(2H)-yl)phenyl)-1H-pyrazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-pyrazol-3-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(3-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-methyl-3-oxo-3,4-dihydro-2H-benzo[β][1,4]oxazin-7-yl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(3-methoxy-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide, and
5-Chloro-N-((1-(5-(2-oxopyridin-1(2H)-yl)quinolin-8-yl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
or a pharmaceutically acceptable salt, ester, or prodrug thereof.

114 more elements

Dependencies are inferred from the claim text.

Facts

Application: 11/620,615Filed 5 Jan 2007
Priority: 18 Jun 2004
Published: 9 Aug 2007
Term ends: Not estimatedThe source records don’t support an estimate.

Classification13 codes

C07D 409/14
Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms: containing three…
A61P 7/02
Drugs for disorders of the blood or the extracellular fluid: antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
A61P 9/00
Drugs for disorders of the cardiovascular system
A61P 9/10
Drugs for disorders of the cardiovascular system: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary…

Family

Application60/580,899Us provisional application · filed 18 Jun 2004
Application11/158,274Continuation in part · filed 20 Jun 2005
Application11/620,615Continuation in part · filed 5 Jan 2007
US 2006/0100193 A1Published application
US 7,521,470 B2Related patent
US 7,696,352 B2Related patent
US 2007/0185092 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound of Formula (I) or a pharmaceutically acceptable salt, ester, or prodrug thereof

wherein:
R1 is selected from the group consisting of halogen, C1-8 alkyl, C2-8 alkenyl, and C2-8 alkynyl;
R2 is hydrogen or C1-4 alkyl;
A is selected from the group consisting of:
wherein the wavy line indicates the point of attachment ring B and the dashed line indicates the point of attachment to the rest of the molecule;
R3 is independently hydrogen or R3a;
R3a is independently selected from the group consisting of halogen, C1-8 alkyl, C2-8 alkenyl, and C2-8 alkynyl;
m is 0, 1, 2, or 3;
X is C—R4 or N or X and Y are C and are fused to a 6-membered aryl, heteroaryl, or heterocyclic ring;
Y is C—R5 or N provided that X and Y are not both N;
R4 is selected from the group consisting of hydrogen, halogen, and
R4a is hydrogen or C1-8 alkyl;
R5 is selected from the group consisting of hydrogen, halogen, and C1-8 alkoxy;
or R5 and R6 together join to form a 6-membered aryl, heteroaryl, or heterocyclic ring fused to ring B;
R6 is selected from the group consisting of —R6a, —NR7aR7b, —NR7aC(O)R7c, —NR7aC(O)OR7c, —CONR8aR8b, —OR7c, —SR7c, —C(═NR7a)NR8aR8b, —S(O)2NR8aR8b, and —S(O)2R7c;
R6a is selected from the group consisting of
wherein R8 can be at any position suitable for a substituent, and if R8 is attached to a nitrogen atom, then it replaces the hydrogen atom attached thereto;
R7a and R7b are independently selected from the group consisting of hydrogen, C1-8 alkyl, and C1-8 alkyl substituted with one to three R9;
R7c is selected from the group consisting of aryl, heteroaryl, C1-8 alkyl, and C1-8 alkyl substituted with one to three R9;
R8 is independently selected from the group consisting of nitro, hydroxy, —CO2H, —C(O)R8c, —C(O)NR8aR8b, —NR8aR8b, —SO2NR8aR8b, halogen, C1-8 alkyl, and C1-8 alkoxy wherein said C1-8 alkyl and C1-8 alkoxy are optionally substituted with one to three R9;
R8a and R8b are independently selected from the group consisting of hydrogen, C1-8 alkyl, and C1-8 alkyl substituted with one to three R9, or R8a and R8b together form a 5 to 7 membered heterocyclic ring optionally substituted with one to three R9 and optionally having one additional ring heteroatom selected from N, O, or S;
R8c is selected from the group consisting of C1-8 alkyl and C1-8 alkyl substituted with one to three R9;
R9 is independently selected from the group consisting of halogen, heterocyclic, heteroaryl, —OH, —R10, —OR10, —SR10, —S(O)R10, —S(O)2R10, —SO2NH2, —C(O)NH2, —C(O)R10, —C(NH)R10, —NHC(O)R10, —NHC(NH)R10, —NHC(O)NH2, —CO2H, —NH2, —NHR10, —N(R10)2 and —N(R10)3+;
each R10 is independently C1-6 alkyl;
and
n is 0, 1, 2, or 3;
provided that when X is C—R4, Y is C—R5, R6 is R6a, and A is
then R6a is bound to ring B through a carbon atom.

25 more elements

Facts

Application

11/620,615Filed 5 Jan 2007

Priority

18 Jun 2004

Published

9 Aug 2007

Term ends

Not estimatedThe source records don’t support an estimate.

Classification13 codes

C07D 409/14
Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms: containing three…
A61P 7/02
Drugs for disorders of the blood or the extracellular fluid: antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
A61P 9/00
Drugs for disorders of the cardiovascular system
A61P 9/10
Drugs for disorders of the cardiovascular system: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary…

Family

Application60/580,899Us provisional application · filed 18 Jun 2004

Application11/158,274Continuation in part · filed 20 Jun 2005

Application11/620,615Continuation in part · filed 5 Jan 2007

US 2006/0100193 A1Published application

US 7,521,470 B2Related patent

US 7,696,352 B2Related patent

US 2007/0185092 A1This patent

From the US filing history. Foreign family members aren’t listed.