US 2008/0293704 A1Published application

FACTOR Xa INHIBITORS

AssigneeMillennium Pharmaceuticals, Inc.

InventorsZhaozhong J. Jia, Yonghong Song, Robert M. Scarborough, Carroll Scarborough, Anjali Pandey

Life of this patent

Estimating the term…

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 intermediates used in making such compounds, pharmaceutical compositions containing such compounds, methods to prevent or treat certain conditions characterized by undesired thrombosis and methods of inhibiting the coagulation of a blood sample.

Claims21

Dependent claims

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

wherein
R1 is halogen;
R2 is hydrogen or halogen;
R3 is selected from the group consisting of —NO2, —NR5aR5b, -L-NR5aR5b, —NHC(O)NR5aR5b, —NHC(O)R5c, —NHC(O)Y, C1-6 alkyl, —CO2H, —C(O)NR5aR5b, —C(O)NR5aY, —C(O)NH-L-Y, OH, C1-6 alkoxy, —O-L-NR5aRb, —O-L-O—C(O)NR5aR5b, —Y, —O—Y, —O-L-Y, —O-L-Y-L-Y, and —S(O)pR5c, wherein said C1-6 alkyl and C1-6 alkoxy are optionally substituted with one to three substituents selected from R6;
R4 is independently selected from the group consisting of halogen, OH, —O-L-Y, —O-L-NR5aRb, and C1-6 alkoxy optionally substituted with one to three substituents selected from R6;
L is C1-C4 alkylene;
Y is aryl, heteroaryl, or heterocyclic ring, wherein said aryl and heteroaryl are optionally substituted with one to three R6 and said heterocyclic ring is optionally substituted with oxo and optionally with one to three R6 or R8;
R5a and R5b are independently hydrogen or C1-8 alkyl optionally substituted with one to three R6, or R5a and R5b together with the nitrogen atom to which they are both attached to form a 5 to 7 membered heterocyclic ring optionally having one additional ring heteroatom selected from N, NR6, O, or S(O)p and where said ring is optionally substituted with one to three substituents selected from R6;
R5c is C1-8 alkyl optionally substituted with one to three R6;
R6 is independently selected from the group consisting of halogen, —OH, —R7, —OR7, oxo, —SR7, —S(O)R7, —S(O)2R7, —SO2NH2, —C(O)NH2, —C(O)R7, —C(NH)R7, —NHC(O)R7, —NHC(NH)R7, —NHC(O)NH2, —CO2H, —NH2, —NHR7, —N(R7)2;
R7 is independently C1-6 alkyl;
R8 is -L-heteroaryl optionally substituted with one to three substituents selected from R6;
n is 0, 1, or 2;
p is 0, 1, or 2;
and
the dashed lines are independently single or double bonds;
provided that R3 is not
where R11 is hydrogen or alkyl.

15 more elements

A compound that is selected from the group consisting of:

5-Chloro-N-((1-(2-(methylamino)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(dimethylamino)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(pyrrolidin-1-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(piperidin-1-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-morpholino-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-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-(2-(4-methyl-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-(2-(4-ethyl-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-(2-(4-isopropyl-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-(2-oxopyridin-1(2H)-yl)-2-thiomorpholinophenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-((1-oxo-)thiomorpholino)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-((1,1-dioxo-)thiomorpholino)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
N-((1-(2-(4-Acetylpiperazin-1-yl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
5-Chloro-N-((1-(2-(4-(1-iminoethyl)piperazin-1-yl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
4-(2-(4-((2-Chlorothiophene-5-carboxamido)methyl)-1H-1,2,3-triazol-1-yl)-5-(2-oxopyridin-1(2H)-yl)phenyl)piperazine-1-carboxamide,
5-Chloro-N-((1-(2-(4-(dimethylamino)piperidin-1-yl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
N-((1-(2-(4-Aminopiperidin-1-yl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
N-((1-(2-(4-Acetamidopiperidin-1-yl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
N-((1-(2-(4-Acetamidinopiperidin-1-yl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
1-(1-(2-(4-((2-Chlorothiophene-5-carboxamido)methyl)-1H-1,2,3-triazol-1-yl)-5-(2-oxopyridin-1(2H)-yl)phenyl)piperidin-4-yl)urea,
5-Chloro-N-((1-(2-(4-hydroxypiperidin-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-((R)-3-hydroxypiperidin-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-((S)-3-hydroxypiperidin-1-yl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
1-(2-(4-((2-Chlorothiophene-5-carboxamido)methyl)-1H-1,2,3-triazol-1-yl)-5-(2-oxopyridin-1(2H)-yl)phenyl)piperidine-4-carboxylic acid,
1-(2-(4-((2-Chlorothiophene-5-carboxamido)methyl)-1H-1,2,3-triazol-1-yl)-5-(2-oxopyridin-1(2H)-yl)phenyl)piperidine-4-carboxamide,
5-Chloro-N-((1-(2-(2-hydroxyethylamino)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(2-methoxyethylamino)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-((2-hydroxyethyl)(methyl)amino)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-((2-methoxyethyl)(methyl)amino)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
N-((1-(2-(2-Aminoethylamino)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
5-Chloro-N-((1-(2-(2-(dimethylamino)ethylamino)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-((2-(dimethylamino)ethyl)(methyl)amino)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(3-hydroxypropylamino)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(3-methoxypropylamino)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-((3-hydroxypropyl)(methyl)amino)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-((3-methoxypropyl)(methyl)amino)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
N-((1-(2-(3-Aminopropylamino)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
5-Chloro-N-((1-(2-(3-(dimethylamino)propylamino)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-((3-(dimethylamino)propyl)(methyl)amino)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(methyl(3-(methylamino)propyl)amino)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(methyl(2-(methylamino)ethyl)amino)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
N-((1-(2-(1H-Imidazol-1-yl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(2-oxopyrrolidin-1-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-nitro-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
N-((1-(2-Amino-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
1-(2-(4-((2-Chlorothiophene-5-carboxamido)methyl)-1H-1,2,3-triazol-1-yl)-5-(2-oxopyridin-1(2H)-yl)phenyl)urea,
N-((1-(2-Acetamido-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
N-(2-(4-((2-Chlorothiophene-5-carboxamido)methyl)-1H-1,2,3-triazol-1-yl)-5-(2-oxopyridin-1(2H)-yl)phenyl)isonicotinamide,
N-(2-(4-((2-Chlorothiophene-5-carboxamido)methyl)-1H-1,2,3-triazol-1-yl)-5-(2-oxopyridin-1(2H)-yl)phenyl)nicotinamide,
5-Chloro-N-((1-(2-(methylthio)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(methylsulfoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(methylsulfonyl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
N-((1-(2-(2-Aminoethylthio)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
N-((1-(2-(2-Aminoethylsulfoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
N-((1-(2-(2-Aminoethylsulfonyl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
5-Chloro-N-((1-(2-methoxy-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(piperidin-4-yloxy)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
N-((1-(2-(1-Acetylpiperidin-4-yloxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
4-(2-(4-((2-Chlorothiophene-5-carboxamido)methyl)-1H-1,2,3-triazol-1-yl)-5-(2-oxopyridin-1(2H)-yl)phenoxy)piperidine-1-carboxamide,
5-Chloro-N-((1-(2-(1-methylpiperidin-4-yloxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(1-isopropylpiperidin-4-yloxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(2-oxopiperidin-4-yloxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(pyridin-4-yloxy)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(pyridin-3-yloxy)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(tetrahydro-2H-thiopyran-4-yloxy)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(1,1-dioxo-tetrahydro-2H-thiopyran-4-yloxy)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(3-(1,3-dioxoisoindolin-2-yl)propoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
N-((1-(2-(3-Aminopropoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
N-((1-(2-(3-Acetamidopropoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
1-(3-(2-(4-((2-Chlorothiophene-5-carboxamido)methyl)-1H-1,2,3-triazol-1-yl)-5-(2-oxopyridin-1(2H)-yl)phenoxy)propyl)urea,
N-((1-(2-(2-Aminoethoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
N-((1-(2-(2-Acetamidoethoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
1-(2-(2-(4-((2-Chlorothiophene-5-carboxamido)methyl)-1H-1,2,3-triazol-1-yl)-5-(2-oxopyridin-1(2H)-yl)phenoxy)ethyl)urea,
5-Chloro-N-((1-(2-(3-hydroxypropoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(2-hydroxyethoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(2-methoxyethoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(3-methoxypropoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-((R)-2,3-dihydroxypropoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-((S)-2,3-dihydroxypropoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(2-(methylsulfonyl)ethoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(2-(aminosulfonyl)ethoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(2-(ethylsulfonyl)ethoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(3-(methylsulfonyl)propoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(3-(aminosulfonyl)propoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(2-(dimethylamino)ethoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(2-(dimethyl(dimethylamino)amino)ethoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(2-(methylamino)ethoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(2-(piperidin-1-yl)ethoxy)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(2-morpholinoethoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(2-(pyridin-4-yl)ethoxy)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(3-(dimethylamino)propoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(3-(pyrrolidin-1-yl)propoxy)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(3-(piperidin-1-yl)propoxy)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(3-morpholinopropoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
2-(2-(4-((2-Chlorothiophene-5-carboxamido)methyl)-1H-1,2,3-triazol-1-yl)-5-(2-oxopyridin-1(2H)-yl)phenoxy)acetic acid,
N-((1-(2-(2-Amino-2-oxoethoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
N-((1-(2-((1H-Tetrazol-5-yl)methoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(trifluoromethoxy)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
2-(4-((2-Chlorothiophene-5-carboxamido)methyl)-1H-1,2,3-triazol-1-yl)-5-(2-oxopyridin-1(2H)-yl)benzoic acid,
N-((1-(2-Carbamoyl-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
5-Chloro-N-((1-(2-(methylcarbamoyl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(dimethylcarbamoyl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
N-((1-(2-((2-Hydroxyethyl)carbamoyl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
N-((1-(2-((3-Hydroxypropyl)carbamoyl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
N-((1-(2-((2-Methoxyethyl)carbamoyl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
N-((1-(2-((2-Aminoethyl)carbamoyl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
N-((1-(2-((2-Amino-2-oxoethyl)carbamoyl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
N-((1-(2-((2-(Dimethylamino)ethyl)carbamoyl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
5-Chloro-N-((1-(2-(methyl(2-(methylamino)ethyl)carbamoyl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-((2-(dimethylamino)ethyl)(methyl)carbamoyl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
N-((1-(2-(3-aminopropylcarbamoyl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(piperazine-1-carbonyl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(2-oxopiperazine-4-carbonyl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(4-hydroxypiperidine-1-carbonyl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
1-(2-(4-((5-Chlorothiophene-2-carboxamido)methyl)-1H-1,2,3-triazol-1-yl)-5-(2-oxopyridin-1(2H)-yl)benzoyl)piperidine-4-carboxamide,
N-((1-(2-(((1H-Tetrazol-5-yl)methyl)carbamoyl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(pyridin-4-ylcarbamoyl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(hydroxymethyl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
N-((1-(2-(Aminomethyl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
5-Chloro-N-((1-(2-((dimethylamino)methyl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(piperidin-1-ylmethyl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(methylthiomethyl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(methylsulfonylmethyl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(pyridin-4-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(pyridin-3-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(pyrimidin-5-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(1H-pyrazol-3-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-((4-aminophenyl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-((4-hydroxyphenyl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-((3-aminophenyl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-((3-hydroxyphenyl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(2-chloropyridin-4-yl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(2-fluoropyridin-4-yl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(6-chloropyridin-3-yl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(6-fluoropyridin-3-yl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(2-hydroxypyridin-4-yl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(2-methoxypyridin-4-yl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
N-((1-(2-(2-Aminopyridin-4-yl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
5-Chloro-N-((1-(2-(2-(dimethylamino)pyridin-4-yl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(2-(methylamino)pyridin-4-yl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(6-hydroxypyridin-3-yl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(6-methoxypyridin-3-yl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
N-((1-(2-(6-Aminopyridin-3-yl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
5-Chloro-N-((1-(2-(6-(dimethylamino)pyridin-3-yl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(6-(methylamino)pyridin-3-yl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
N-((1-(2-(3-Amino-3-oxopropylcarbamoyl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
N-((1-(2-(2-(1H-Imidazol-1-yl)ethoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(2-(pyridin-4-yl)ethoxy)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
3-(2-(4-((5-Chlorothiophene-2-carboxamido)methyl)-1H-1,2,3-triazol-1-yl)-5-(2-oxopyridin-1(2H)-yl)phenoxy)propyl morpholine-4-carboxylate,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(pyridin-2-yloxy)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamid,
2-(2-(4-((5-Chlorothiophene-2-carboxamido)methyl)-5-iodo-1H-1,2,3-triazol-1-yl)-5-(2-oxopyridin-1(2H)-yl)phenoxy)acetic acid,
5-Chloro-N-((1-(2-(3-hydroxypropoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-5-iodo-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-((R)-2,3-dihydroxypropoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-5-iodo-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-((S)-2,3-dihydroxypropoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-5-iodo-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
N-((1-(2-(2-(1H-Pyrazol-1-yl)ethoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopiperidin-1-yl)-2-thiomorpholinophenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopiperidin-1-yl)-2-((1,1-dioxo)thiomorpholino)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(3-oxopiperazin-1-yl)-4-(2-oxopiperidin-1-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-(morpholinomethyl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-((3-oxopiperazin-1-yl)methyl)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(thiomorpholinomethyl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(1,1,-dioxothiomorpholinomethyl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-ethoxy-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(pyridin-3-ylmethoxy)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(N-(pyridine-3-yl)pyridin-3-ylmethoxy)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(pyridin-4-ylmethoxy)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(2-(pyridin-2-yl)ethoxy)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(pyridin-2-ylmethoxy)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(quinolin-2-ylmethoxy)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(thiazol-4-ylmethoxy)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
5-Chloro-N-((1-(2-((2-methylthiazol-4-yl)methoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
N-((1-(2-((1H-Benzo[d]imidazol-2-yl)methoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
5-Chloro-N-((1-(4-(2-oxopyridin-1(2H)-yl)-2-(2-(pyridin-3-yl)ethoxy)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
N-((1-(2-((1,2,4-Oxadiazol-3-yl)methoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
5-Chloro-N-((1-(2-((1-methyl-1H-imidazol-2-yl)methoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
N-((1-(2-((1H-Imidazol-2-yl)methoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
N-((1-(2-((1-((1H-imidazol-2-yl)methyl)-1H-imidazol-2-yl)methoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
5-Chloro-N-((1-(2-((5-methylisoxazol-3-yl)methoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)thiophene-2-carboxamide,
N-((1-(2-(2-(1H-Pyrrol-1-yl)ethoxy)-4-(2-oxopyridin-1(2H)-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)-5-chlorothiophene-2-carboxamide,
or a pharmaceutically acceptable salt, ester, or prodrug thereof.

178 more elements

Dependencies are inferred from the claim text.

Facts

Application: 11/969,758Filed 4 Jan 2008
Priority: 5 Jan 2007
Published: 27 Nov 2008
Term ends: Not estimatedThe source records don’t support an estimate.

Classification9 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 7/00
Drugs for disorders of the blood or the extracellular fluid
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

Family

Application60/883,734Us provisional application · filed 5 Jan 2007
US 2008/0293704 A1This patent

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

Timeline

Citations

Open elsewhere

patentgrep

Loading patent…

Abstract

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

wherein
R1 is halogen;
R2 is hydrogen or halogen;
R3 is selected from the group consisting of —NO2, —NR5aR5b, -L-NR5aR5b, —NHC(O)NR5aR5b, —NHC(O)R5c, —NHC(O)Y, C1-6 alkyl, —CO2H, —C(O)NR5aR5b, —C(O)NR5aY, —C(O)NH-L-Y, OH, C1-6 alkoxy, —O-L-NR5aRb, —O-L-O—C(O)NR5aR5b, —Y, —O—Y, —O-L-Y, —O-L-Y-L-Y, and —S(O)pR5c, wherein said C1-6 alkyl and C1-6 alkoxy are optionally substituted with one to three substituents selected from R6;
R4 is independently selected from the group consisting of halogen, OH, —O-L-Y, —O-L-NR5aRb, and C1-6 alkoxy optionally substituted with one to three substituents selected from R6;
L is C1-C4 alkylene;
Y is aryl, heteroaryl, or heterocyclic ring, wherein said aryl and heteroaryl are optionally substituted with one to three R6 and said heterocyclic ring is optionally substituted with oxo and optionally with one to three R6 or R8;
R5a and R5b are independently hydrogen or C1-8 alkyl optionally substituted with one to three R6, or R5a and R5b together with the nitrogen atom to which they are both attached to form a 5 to 7 membered heterocyclic ring optionally having one additional ring heteroatom selected from N, NR6, O, or S(O)p and where said ring is optionally substituted with one to three substituents selected from R6;
R5c is C1-8 alkyl optionally substituted with one to three R6;
R6 is independently selected from the group consisting of halogen, —OH, —R7, —OR7, oxo, —SR7, —S(O)R7, —S(O)2R7, —SO2NH2, —C(O)NH2, —C(O)R7, —C(NH)R7, —NHC(O)R7, —NHC(NH)R7, —NHC(O)NH2, —CO2H, —NH2, —NHR7, —N(R7)2;
R7 is independently C1-6 alkyl;
R8 is -L-heteroaryl optionally substituted with one to three substituents selected from R6;
n is 0, 1, or 2;
p is 0, 1, or 2;
and
the dashed lines are independently single or double bonds;
provided that R3 is not
where R11 is hydrogen or alkyl.

15 more elements

Facts

Application

11/969,758Filed 4 Jan 2008

Priority

5 Jan 2007

Published

27 Nov 2008

Term ends

Not estimatedThe source records don’t support an estimate.

Classification9 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 7/00
Drugs for disorders of the blood or the extracellular fluid
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