Factor xa inhibitors

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.

1 - 19 . (canceled) 
   
   
       20 . A method for preventing or treating thrombosis in a mammal comprising administering to said mammal a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt, ester, prodrug or composition thereof 
     
       
         
         
             
             
         
       
       wherein: 
       R 1  is selected from the group consisting of halogen, C 1-8  alkyl, C 2-8  alkenyl, and C 2-8  alkynyl; 
       R 2  is hydrogen or C 1-4  alkyl; 
       A is selected from the group consisting of: 
     
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
        wherein the wavy line indicates the point of attachment to ring B and the dashed line indicates the point of attachment to the rest of the molecule; 
       R 3  is independently hydrogen or R 3a ; 
       R 3a  is independently selected from the group consisting of halogen, C 1-8  alkyl, C 2-8  alkenyl, and C 2-8 alkynyl; 
       m is 0, 1, 2, or 3; 
       X is C—R 4  or N or X and Y are C and are fused to a 6-membered aryl, heteroaryl, or heterocyclic ring; 
       Y is C—R 5  or N provided that X and Y are not both N; 
       R 4  is selected from the group consisting of hydrogen, halogen, and 
     
     
       
         
         
             
             
         
       
       R 4a  is hydrogen or C 1-8  alkyl; 
       R 5  is selected from the group consisting of hydrogen, halogen, and C 1-8 alkoxy; or R 5  and R 6  together join to form a 6-membered aryl, heteroaryl, or heterocyclic ring fused to ring B; 
       R 6  is selected from the group consisting of —R 6a , —NR 7a R 7b , —NR 7a C(O)R 7c , —NR 7a C(O)OR 7c , —CONR 8a R 8b , —OR 7c , —SR 7c , —C(═NR 7a )NR 8a R 8b , —S(O) 2 NR 8a R 8b , and —S(O) 2 R 7c ; 
       R 6a  is selected from the group consisting of 
     
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
        wherein R 8  can be at any position suitable for a substituent, and if R 8  is attached to a nitrogen atom, then it replaces the hydrogen atom attached thereto; 
       R 7a  and R 7b  are independently selected from the group consisting of hydrogen, C 1-8  alkyl, and C 1-8  alkyl substituted with one to three R 9 ; 
       R 7c  is selected from the group consisting of aryl, heteroaryl, C 1-8  alkyl, and C 1-8  alkyl substituted with one to three R 9 ; 
       R 8  is independently selected from the group consisting of nitro, hydroxyl, —CO 2 H, —C(O)R 8c , —C(O)NR 8a R 8b , —NR 8a R 8b , —SO 2 NR 8a R 8b , halogen, C 1-8  alkyl, and C 1-8  alkoxy wherein said C 1-8  alkyl and C 1-8  alkoxy are optionally substituted with one to three R 9 ; 
       R 8a  and R 8b  are independently selected from the group consisting of hydrogen, C 1-8  alkyl, and C 1-8  alkyl substituted with one to three R 9 , or R 8a  and R 8b  together form a 5 to 7 membered heterocyclic ring optionally substituted with one to three R 9  and optionally having one additional ring heteroatom selected from N, O, or S; 
       R 8c  is selected from the group consisting of C 1-8  alkyl and C 1-8  alkyl substituted with one to three R 9 ; 
       R 9  is independently selected from the group consisting of halogen, heterocyclic, heteroaryl, —OH, —R 10 , —OR 10 , —SR 10 , —S(O)R 10 , —S(O) 2 R 10 , —SO 2 NH 2 , —C(O)NH 2 , —C(O)R 10 , —C(NH)R 10 , —NHC(O)R 10 , —NHC(NH)R 10 , —NHC(O)NH 2 , —CO 2 H, —NH 2 , —NHR 10 , —N(R 10 ) 2  and —N(R 10 ) 3   + ; 
       each R 10  is independently C 1-6  alkyl; and 
       n is 0, 1, 2, or 3; 
       provided that when X is C—R 4 , Y is C—R 5 , R 6  is R 6a , and A is 
     
     
       
         
         
             
             
         
       
       then R 6a  is bound to ring B through a carbon atom. 
     
   
   
       21 . The method of  claim 20  wherein R 1  is 2-chloro. 
   
   
       22 . The method of  claim 20  wherein R 2  is hydrogen. 
   
   
       23 . The method of  claim 20  wherein X and Y are CH. 
   
   
       24 . The method of  claim 20  wherein A is selected from the group consisting of: 
     
       
         
         
             
             
         
       
     
   
   
       25 . The method of  claim 20  wherein R 6  is R 6a . 
   
   
       26 . The method of  claim 25  wherein R 6a  is selected from the group consisting of: 
     
       
         
         
             
             
         
       
     
   
   
       27 . The method of  claim 20  wherein R 6  is selected from the group consisting of: 
     
       
         
         
             
             
         
       
       
         
         
             
             
         
       
     
   
   
       28 . The method of  claim 20  wherein R 6  is selected from the group consisting of: 
     
       
         
         
             
             
         
       
     
   
   
       29 . The method of  claim 20  wherein R 6  is selected from the group consisting of: 
     
       
         
         
             
             
         
       
     
   
   
       30 . The method of  claim 20  wherein R 6  is selected from the group consisting of: 
     
       
         
         
             
             
         
       
     
   
   
       31 . The method of  claim 20  wherein R 6  is selected from the group consisting of: 
     
       
         
         
             
             
         
       
     
   
   
       32 . The method of  claim 20  wherein R 6  is 
     
       
         
         
             
             
         
       
     
     and R 8  is as previously defined. 
   
   
       33 . The method of  claim 32 , wherein R 8  is selected from the group consisting of: hydrogen, 
     
       
         
         
             
             
         
       
     
   
   
       34 . The method of  claim 20  wherein the compound is 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-(T-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-(44(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(2′-1)-yl)pyridin-2-yl)-1H-imidazol-4-yl)methyl)thiophene-2-carboxamide,   5-Chloro-N-((1-(6-(2-oxopyridin-1(2H)-yl)pyri din-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(211)-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-N-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-N-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.   
   
   
       35 . The method of  claim 20 , wherein the thrombosis is associated with a condition selected from the group consisting of acute coronary syndrome, myocardial infarction, unstable angina, refractory angina, occlusive coronary thrombus occurring post-thrombolytic therapy or post-coronary angioplasty, a thrombotically mediated cerebrovascular syndrome, embolic stroke, thrombotic stroke, transient ischemic attacks, venous thrombosis, deep venous thrombosis, pulmonary embolus, coagulopathy, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, thromboangiitis obliterans, thrombotic disease associated with heparin-induced thrombocytopenia, thrombotic complications associated with extracorporeal circulation, thrombotic complications associated with instrumentation such as cardiac or other intravascular catheterization, intra-aortic balloon pump, coronary stent or cardiac valve, and conditions requiring the fitting of prosthetic devices. 
   
   
       36 . The method of  claim 35 , wherein the condition is selected from the group consisting of embolic stroke, thrombotic stroke, venous thrombosis, deep venous thrombosis, acute coronary syndrome, and myocardial infarction.