Sulfonic acid or sulfonylamino N-(heteroaralkyl)-azaheterocyclylamide compounds

Abstract

The compounds of formula I herein exhibit useful pharmacological activity and accordingly are incorporated into pharmaceutical compositions and used in the treatment of patients suffering from certain medical disorders. More specifically, they are inhibitors of the activity of Factor Xa. The present invention is directed to compounds of formula I, compositions containing compounds of formula I, and their use, for treating a patient suffering from, or subject to, a physiological condition which can be ameliorated by the administration of an inhibitor of the activity of Factor Xa.

What is claimed is:  
     
         1 .  
       
         
           
           
               
               
           
         
         wherein  
         
           
             
             
                 
                 
             
           
         
          is a monocyclic heteroaryl group containing at least one nitrogen atom, or a bicyclic heteroaryl group which includes a first proximal ring that is attached to Z and a ring distal to said first ring, said distal ring including at least one nitrogen atom;  
         Z is alkylenyl, —(CH 2 ) r C(O)NR″(CH 2 ) s —, —(CH 2 ) s R″NC(O)(CH 2 ) r —, —(CH 2 ) r NR″(CH 2 ) s — or  
         —(CH 2 ) s ,NR″(CH 2 ) r —;  
         R 1  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, R′O(CH 2 ) x —, R′O 2 C(CH 2 ) x —, R′C(O)(CH 2 ) x —, Y 1 Y 2 NC(O)CH 2 ) x —, or Y 1 Y 2 (CH 2 ) x —;  
         R′ and R″ are independently hydrogen, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkenyl, optionally substituted heteroaralkenyl, optionally substituted aralkyl or optionally substituted heteroaralkyl;  
         R 2  is hydrogen, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted aralkenyl, optionally substituted heteroaralkenyl, R 3 R 4 NC(O)(CH 2 ) x —, R 3 S(O) p — or R 3 R 4 NS(O) p —;  
         R 3  is hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted aralkenyl or optionally substituted heteroaralkenyl, or R 1  and R 3  taken together with the —N—S(O) p —NR 4 — moiety or the -N-S(O)p-NR 4 - moiety through which R 1  and R 3  are linked form a 5 to 7 membered optionally substituted heterocyclyl; and  
         R 4  is hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl or optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl or optionally substituted heteroaralkyl, or R 3  and R 4  taken together with the nitrogen to which R 3  and R 4  are attached form an optionally substituted 4 to 7 membered heterocyclyl;  
         X 1  and X 1a  are independently selected from H, optionally substituted alkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, or X 1  and X 1a  taken together form oxo;  
         X 2  and X 2a  are H, or taken together form oxo;  
         X 3  is H, hydroxy, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl or optionally substituted heteroaralkyl, or X 3  and one of X 1  and X 1a  taken together form a 4 to 7 membered cycloalkyl;  
         X 4  is H, optionally substituted alkyl, optionally substituted aralkyl, or hydroxyalkyl;  
         X 5 , X 5a  and X 5b  are independently selected from H, R 5 R 6 N—, (hydroxy)HN—, (alkoxy)HN—, or (amino)HN—, R 7 O—, R 5 R 6 NCO—, R 5 R 6 NSO 2 —, R 7 CO—, halo, cyano, nitro and R 8 (O)C(CH 2 ) q —, and when  
         
           
             
             
                 
                 
             
           
         
          is a bicyclic heteroaryl group, one of X 5 , X 5a  and X 5b  is a substituent that is alpha to a nitrogen of said distal ring of  
         
           
             
             
                 
                 
             
           
         
          and is selected from the group consisting of H, hydroxy and H 2 N—, (optionally substituted lower alkyl)HN (hydroxy)HN—, (alkoxy)HN—, or (amino)HN—;  
         Y 1  and Y 2  are independently hydrogen, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl or optionally substituted heteroaralkyl, or Y 1  and Y 2  taken together with the N through which Y 1  and Y 2  are linked form a 4 to 7 membered heterocyclyl;  
         R 5  and R 6  are independently H or optionally substituted lower alkyl, or one of R 5  and R 6  is H and the other of R 5  and R 6  is R 8 (O)CCH 2 — or lower acyl;  
         R 7  is H, optionally substituted lower alkyl, lower acyl or R 8 (O)CCH 2 —;  
         R 8  is H, optionally substituted lower alkyl, alkoxy or hydroxy;  
         m is 0, 1, 2or 3;  
         p and r are independently 1 or 2;  
         q is 0 or 1,  
         s is 0, 1 or 2; and  
         x is 1, 2, 3, 4, or 5, or  
         a pharmaceutically acceptable salt thereof, an N-oxide thereof, a hydrate thereof or a solvate thereof.  
       
     
     
         2 .  
       
         
           
           
               
               
           
         
         wherein  
         
           
             
             
                 
                 
             
           
         
          is a bicyclic heteroaryl which includes a first proximal ring that is attached to Z and a ring distal to said first ring, said distal ring including at least one nitrogen atom;  
         Z is alkylenyl;  
         R 1  is hydrogen, optionally substituted alkyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, R′O(CH 2 ) x —, R′O 2 C(CH 2 ) x —, Y 1 Y 2 NC(O)(CH 2 ) x —, or Y 1 Y 2 N(CH 2 ) x —;  
         R′ is hydrogen, optionally substituted alkyl, optionally substituted aralkyl or optionally substituted heteroaralkyl;  
         R 2  is R 3 S(O) p — or R 3 R 4 NS(O) p —;  
         R 3  is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl, optionally substituted heteroaralkyl, optionally substituted aralkenyl or optionally substituted heteroaralkenyl, or R 1  and R 3  taken together with the —N—S(O) p — moiety or the —N—S(O) p —NR 4 — moiety through which R 1  and R 3  are linked form a 5 to 7 membered optionally substituted heterocyclyl; and  
         R 4  is optionally substituted alkyl, optionally substituted cycloalkyl or optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl or optionally substituted heteroaralkyl, or R 3  and R 4  taken together with the nitrogen to which R 3  and R 4  are attached form an optionally substituted 4 to 7 membered heterocyclyl;  
         X 1  and X 1a  are independently selected from H, optionally substituted alkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl or optionally substituted heteroaralkyl, or X 1  and X 1a  taken together form oxo;  
         X 2  and X 2a  are H, or taken together form oxo;  
         X 3  is H, hydroxy, optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted aralkyl or optionally substituted heteroaralkyl, or X 3  and one of X 1  and X 1a  taken together form a 4 to 7 membered cycloalkyl;  
         X 4  is H, optionally substituted alkyl, optionally substituted aralkyl, or hydroxyalkyl;  
         X 5 , X 5a  and X5b are independently selected from H, R 5 R 6 N—, (hydroxy, alkoxy or amino)HN—, R 7 O—, R 5 R 6 NCO—, R 5 R 6 NSO 2 —, R 7 CO—, halo, cyano, nitro or R 8 (O)C(CH 2 ) q —, and one of X 5 , X 5a , and X 5b  is a substituent that is alpha to a nitrogen of said distal ring of  
         
           
             
             
                 
                 
             
           
         
          and is selected from the group consisting of H, hydroxy or H 2 N—, (optionally substituted lower alkyl)HN (hydroxy)HN—, (alkoxy)HN—, or (amino)HN—;  
         Y 1  and Y 2  are independently hydrogen, optionally substituted alkyl, optionally substituted aryl, optionally substituted aralkyl or optionally substituted heteroaralkyl, or Y 1  and Y 2  taken together with the N through which Y 1  and Y 2  are linked form a 4 to 7 membered heterocyclyl;  
         R 5  and R 6  are independently H or optionally substituted lower alkyl, or one of R 5  and R 6  is H and the other of R 5  and R 6  is R 8 (O)CCH 2 — or lower acyl;  
         R 7  is H, optionally substituted lower alkyl, lower acyl or R 8 (O)CCH 2 —;  
         R 8  is H, optionally substituted lower alkyl, alkoxy or hydroxy;  
         m is 0, 1, 2or 3;  
         p is 1 or 2;  
         q is 0 or 1, and  
         x is 1, 2, 3, 4, or 5, or  
         a pharmaceutically acceptable salt thereof, an N-oxide thereof, a hydrate thereof or a solvate thereof.  
       
     
     
         3 . The compound of  claim 1  wherein  
       
         
           
           
               
               
           
         
       
       is a monocyclic heteroaryl group containing at least one nitrogen atom.  
     
     
         4 . The compound of  claim 1  wherein Z is alkylenyl, —(CH 2 ) r C(O)NR″(CH 2 ) s —, —(CH 2 ) s R″NC(O)(CH 2 ) r —, —(CH 2 ) r NR″(CH 2 ) s — or —(CH 2 ) s NR″(CH 2 ) r —.  
     
     
         5 . The compound of  claim 1  wherein R 1  is hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted aralkyl, optionally substituted heteroaralkyl, R′O(CH 2 ) x —, R′O 2 C(CH 2 ) x —, R′(O)(CH 2 ) x —, Y 1 Y 2 NC(O)(CH 2 ) x —, or Y 1 Y 2 N(CH 2 ) x —.  
     
     
         6 . The compound of  claim 1  wherein R 2  is selected from the group consisting of  
       
         
           
           
               
               
           
         
       
     
     
         7 . The compound of  claim 1  wherein  
       
         
           
           
               
               
           
         
       
       is selected from the group consisting of  
       
         
           
           
               
               
           
         
       
     
     
         8 . The compound of  claim 1  wherein R 1  is H, optionally substituted heteroaralkyl, optionally substituted aralkyl or optionally substituted alkyl.  
     
     
         9 . The compound of  claim 1  wherein R 2  is R 3 S(O) p —.  
     
     
         10 . The compound of  claim 9  wherein p is 2.  
     
     
         11 . The compound of  claim 9  wherein R 3  is optionally substituted phenyl, optionally substituted naphthyl, optionally substituted thienyl, optionally substituted benzothienyl, optionally substituted thienyopyridyl, optionally substituted quinolinyl, or optionally substituted isoquinolinyl.  
     
     
         12 . The compound of  claim 1  wherein Z is methylenyl and m is 1.  
     
     
         13 . The compound of  claim 1  wherein X 2  and X 2a  taken together are oxo.  
     
     
         14 . The compound of  claim 1  wherein each of X 1 , X 1a , X 3  and X 4  is H.  
     
     
         15 . The compound of  claim 1  wherein  
       
         
           
           
               
               
           
         
       
       is optionally substituted isoquinolinyl.  
     
     
         16 . The compound of  claim 15  wherein Z is attached to isoquinolinyl at the 7-position thereof.  
     
     
         17 . The compound of  claim 1  wherein  
       
         
           
           
               
               
           
         
       
       is optionally substituted quinolinyl.  
     
     
         18 . The compound of  claim 17  wherein Z is attached to quinolinyl at the 7-position thereof.  
     
     
         19 . The compound of  claim 1  wherein  
       
         
           
           
               
               
           
         
       
       is an optionally substituted quinazolinyl.  
     
     
         20 . The compound of  claim 19  wherein Z is attached to quinazolinyl at the 7-position thereof.  
     
     
         21 . The compound of  claim 1  wherein  
       
         
           
           
               
               
           
         
       
       is an optionally substituted moiety of formula  
       
         
           
           
               
               
           
         
       
       and W is S, O or NR 11 , wherein R 11  is H, alkyl, aralkyl, heteroaralkyl, R 8 (O)C(CH 2 ) q —, and A is CH or N.  
     
     
         22 . The compound of  claim 21  wherein Z is bonded to said moiety through the 5 membered ring.  
     
     
         23 . The compound of  claim 1  wherein one of X 5 , X 5a  and X 5b  is a substituent that is on the proximal ring of bicyclic  
       
         
           
           
               
               
           
         
       
       at a position that is alpha to where Z is attached to  
       
         
           
           
               
               
           
         
       
       and is selected from the group consisting of H, hydroxy and amino.  
     
     
         24 . The compound of  claim 23  wherein one of X 5 , X 5a , and X 5b  is hydroxy or amino.  
     
     
         25 . The compound of  claim 1  wherein one of X 5 , X 5a  and X 5b  that substitutes the distal ring of  
       
         
           
           
               
               
           
         
       
       at the position alpha to a nitrogen thereof is H or (H, optionally substituted loweralkyl, hydroxy or amino)HN—.  
     
     
         26 . A compound according to  claim 1  which is selected from 
 3-[[1-(4-Aminoquinolin-7-ylmethyl)-2-oxopyrrolidin-3-(R)-yl]-(5-chloro-1H-indol-2-ylmethyl)amino]propionic acid methyl ester;  
 1-(4-Aminoquinolin-7-ylmethyl)-3-(R)-[(5-chloro-1H-indol-2-ylmethyl)-(3-ethylbutyl)amino]pyrrolidin-2-one;  
 1-(4-Aminoquinolin-7-ylmethyl)-3-(R)-[benzyl-(5-chloro-1H-indol-2-ylmethyl)amino]pyrrolidin-2-one;  
 1-(4-Aminoquinolin-7-ylmethyl)-3-(R)-[(5-chloro-1H-indol-2-ylmethyl)thiazol-5-ylmethylamino]pyrrolidin-2-one;  
 1-(4-Aminoquinolin-7-ylmethyl)-3-(R)-[(5-chloro-1H-indol-2-ylmethyl-(2H-pyrazol-3-ylmethyl))amino]pyrrolidin-2-one;  
 1-(4-Aminoquinazolin-7-ylmethyl)-3-(S)-[(6-chlorobenzo[b]thiophen-2-ylmethyl)amino]pyrrolidin-2-one;  
 1-(4-Aminoquinazolin-7-ylmethyl)-3-(S)-[(6-chlorothieno[2,3-b]pyridin-2-ylmethyl)amino]pyrrolidin-2-one;  
 1-(4-Aminoquinazolin-7-ylmethyl)-3-(S)-[(1H-pyrrolo[2,3-c]pyridin-2-ylmethyl)amino]pyrrolidin-2-one;  
 3-{[1-(4-Aminoquinazolin-7-ylmethyl)-2-oxopyrrolidin-3-(S)-ylamino]methyl}-1H-quinolin-2-one;  
 1-(7-Aminothieno[3,2-b]pyridin-2-ylmethyl)-3-(R)-[(5-chloro-1H-indol-2-ylmethyl)amino]pyrrolidin-2-one;  
 2-(5-Chlorothiophen-2-yl)ethenesulfonic acid[2-oxo1-(1H-pyrrolo[3,2-c]pyridin-2-ylmethyl)-pyrrolidin3-(R)-yl]amide;  
 {[2-(5-Chlorothiophen-2-yl)ethenesulfonyl]-[2-oxo-1-(1H-pyrrolo[3,2-c]pyridin-2-ylmethyl)-pyrrolidin-3-(R)-yl]amino}acetic acid isopropyl ester;  
 1-(4-Aminoquinolin-7-ylmethyl)-3-(R)-[(5-chloro-1H-indol-2-ylmethyl)amino]pyrrolidin-2-one;  
 5-Chloro-1H-benzoimidazole-2-sulfonic acid[1-(4-aminoquinolin-7-ylmethyl)-2-oxopyrrolidin-3-(R)-yl]amide7-Methoxynaphthalene-2-sulfonic acid[1-(1-aminoisoquinolin-7-yl-methyl)-2-oxopyrrolidin-3-(R,S)-yl]amide trifluoroacetate;  
 7-Methoxynaphthalene-2-sulfonic acid[1-(1-aminoisoquinolin-7-yl-methyl)-2-oxopyrrolidin-3-yl]amide hydrochloride;  
 7-Methoxynaphthalene-2-sulfonic acid[1-(1-aminoisoquinolin-7-yl-methyl)-2-oxopyrrolidin-3-(S)-yl]amide trifluoroacetate;  
 7-Methoxynaphthalene-2-sulfonic acid[1-(1-aminoisoquinolin-7-yl-methyl)-2-oxopyrrolidin-3-(R)-yl]amide trifluoroacetate;  
 7-Methoxynaphthalene-2-sulfonic acid[1-(1-hydroxyisoquinolin-7ylmethyl)-2-oxopyrrolidin-3-(R,S)-yl]amide;  
 7-Methoxynaphthalene-2-sulfonic acid[1-(1-aminoisoquinolin-7-ylmethyl)-2-oxopyrrolidin-3-(R,S)-yl]methylamide trifluoroacetate;  
 7-Methoxynaphthalene-2-sulfonic acid[1-(1-aminoisoquinolin-7-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]methyl amide trifluoroacetate;  
 Benzo[b]thiophene-2-sulfonic acid[1-(1-aminoisoquinolin-7-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]amide trifluoroacetate;  
 6-Chloro-benzo[b]thiophene-2-sulfonic acid[1-(1-aminoisoquinolin-7-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]amide trifluoroacetate;  
 7-Methoxynaphthalene-2-sulfonic acid[1-(1-amino-6-methoxyisoquinolin-7-ylmethyl2-oxopyrrolidin-3-(S)-yl]amide hydrochloride;  
 7-Methoxynaphthalene-2-sulfonic acid[1-(6-methoxyisoquinolin-7-ylmethyl)-2-oxo pyrrolidin-3-(S)-yl]amide trifluoroacetate;  
 4-(2-Chloro-6-nitophenoxy)benzene sulfonic acid[1-(1-amino-6-methoxyisoquinolin-7-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]amide trifluoroacetate;  
 7-Methoxynaphthalene-2-sulfonic acid[1-(1,6-diaminoisoquinolin-7-yl-methyl)-2-oxopyrrolidin-3-(S)-yl]amide trifluoroacetate;  
 6-Chloro-benzo[b]thiophene-2-sulfonic acid[1-(1,6-diaminoisoquinolin-7-yl-methyl)-2-oxo pyrrolidin-3-(S)-yl]amide trifluoroacetate;  
 7-Methoxynaphthalene-2-sulfonic acid[1-(2-aminoquinolin-7-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]amide trifluoroacetate;  
 6-Chloro-benzo[b]thiophene-2-sulfonic acid[1(2-aminoquinolin-7-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]amide trifluoroacetate;  
 Benzo[b]thiophene-2-sulfonic acid[1-(2-aminoquinolin-7-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]amide trifluoroacetate;  
 7-Methoxynaphthalene-2-sulfonic acid[1-(2-aminoquinolin-7-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]methyl amide trifluoroacetate;  
 7-Methoxynaphthalene-2-sulfonic acid[1-(2-hydroxyquinolin-7-ylmethyl)-2-oxopyrrolidin-3-(S)yl]methyl amide;  
 7-Methoxynaphthalene-2-sulfonic acid[1-(2-aminoquinolin-5-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]amide trifluoroacetate;  
 7-Methoxynaphthalene-2-sulfonic acid[1-(2-aminoquinolin-5-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]methyl amide trifluoroacetate;  
 7-Methoxynaphthalene-2-sulfonic acid[1-(2-hydroxyquinolin-5-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]methylamide;  
 7-Methoxynaphthalene-2-sulfonic acid[1-(2-aminoquinolin-6-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]amide;  
 7-Methoxynaphthalene-2-sulfonic acid[1-(2-hydroxyquinolin-6-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]amide;  
 7-Methoxynaphthalene-2-sulfonic acid[1-(1H-benzimidazol-5-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]amide trifluoroacetate;  
 7-Methoxynaphthalene-2-sulfonic acid[2-(1H-benzimidazol-5-ylethyl)-2-oxopyrrolidin-3-(S)-yl]amide trifluoroacetate;  
 7-Methoxynaphthalene-2-sulfonic acid[1-(4-aminoquinazolin-6-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]methylamide trifluoroacetate;  
 7-Methoxynaphthalene-2-sulfonic acid[1-(4-aminothieno[2,3-d]pyrimidin-6-yl-methyl)-2-oxopyrrolidin-3-(S)-yl]amide trifluoroacetate;  
 7-Methoxynaphthalene-2-sulfonic acid[2-(6-aminothieno[2,3-d]pyrimidin-6-yl-methyl)-2-oxopyrrolidin-3-(S)-yl]amide trifluoroacetate;  
 7-Methoxynaphthalene-2-sulfonic acid[1-(7-aminothieno[2,3-c]pyridin-3-yl-methyl)-2-oxopyrrolidin-3-(S)-yl]amide trifluoroacetate;  
 7-Methoxynaphthalene-2-sulfonic acid[1-(7-hydroxythieno[2,3-c]pyridin-3-yl-methyl)-2-oxopyrrolidin-3-(S)-yl]amide trifluoroacetate;  
 7-Methoxynaphthalene-2-sulfonic acid[1-(4-aminothieno[3,2-c]pyridin-3-yl-methyl)-2-oxopyrrolidin-3-(R,S)-yl]amide trifluoroacetate;  
 7-Methoxynaphthalene-2-sulfonic acid[1-(4-hydroxythieno[3,2-c]pyridin-3-yl-methyl)-2-oxopyrrolidin-3-(R,S)-yl]amide trifluoroacetate;  
 Benzo[b]thiophene-2-sulfonic acid[1-(4-aminothieno[3,2-c]pyridin-3-yl-methyl)-2-oxopyrrolidin-3-(R,S)-yl]amide trifluoroacetate;  
 Thieno[3,2-b]pyridine-2-sulfonic acid[1-(1-amino-isoquinolin-7-ylmethyl)-2-oxo-pyrrolidin-3-(S)-yl]-amide;  
 Thieno[2,3-b]pyridine-2-sulfonic acid[1-(1-amino-isoquinolin-7-ylmethyl)-2-oxo-pyrrolidin-3-(S)-yl]-amide;  
 4-Pyridin-3-yl-thiophene-2-sulfonic acid[1-(1-amino-isoquinolin-7-ylmethyl)-2-oxo-pyrrolidin-3-(S)-yl]-amide;  
 5′Chloro-[2,2′]bithiophenyl-5-sulfonic acid[2-oxo-1-(1H-pyrrolo[3,2-c]pyridin-2-ylmethyl)-pyrrolidin-3(S)-yl]-amide;  
 2-(5-Chloro-thiophen-2-yl)-ethenesulfonic acid[2-oxo-1-(1H-pyrrolo[3,2-c]pyridin-2-ylmethyl)-pyrrolidin-3-(S)-yl]-amide;  
 5′-Chloro-[2,2′]bithiophenyl-5-sulfonic acid[1-(1-amino-isoquinolin-7-ylmethyl)-2-oxo-pyrrolidin-3-(S)-yl]-amide;  
 2-(5-Chloro-thiophen-2-yl)-ethenesulfonic acid[1-(1-amino-isoquinolin-7-ylmethyl)-2-oxo-pyrrolidin-3-(S)-yl]-amide;  
 6-Chloro-benzo[b]thiophene-2-sulfonic acid[1-(4-amino-quinazolin-6-yl-methyl)-2-oxopyrrolidin-3-(S)-yl]amide trifluoroacetate;  
 6-Chloro-benzo[b]thiophene-2-sulfonic acid[1-(4-amino-thieno[2,3-d]pyrimidin-6yl-methyl)-2-oxopyrrolidin-3-(S)-yl]amide trifluoroacetate;  
 6-Chloro-benzo[b]thiophene-2-sulfonic acid[1-(4-amino-thieno[3,2-d]pyrimidin-7-yl-methyl)-2-oxopyrrolidin-3-(S)-yl]amide trifluoroacetate;  
 5′-Chloro-[2,2′]bithiophenyl-5-2-sulfonic acid[1-(4-amino-thieno[3,2-d]pyrimidin-7-yl-methyl)-2-oxopyrrolidin-3-(S)-yl]amide trifluoroacetate;  
 Thieno[3,2-b]pyridine-2-sulfonic acid[1-(1,6-diamino-isoquinolin-7-ylmethyl)-2-oxo-pyrrolidin-3-(S)-yl]-amide;  
 2-(5-Chloro-thiophen-2-yl)-ethenesulfonic acid[1-(1-amino-isoquinolin-7-ylmethyl)-2-oxo-pyrrolidin-3-(S)-yl]-amide;  
 5′-Chloro-[2,2′]bithiophenyl-5-sulfonic acid[1-(1-amino-isoquinolin-7-ylmethyl)-2-oxo-pyrrolidin-3-(S)-yl]-amide;  
 2-(5-Chloro-thiophen-2-yl)-ethenesulfonic acid[2-oxo-1-(1H-pyrrolo[3,2-c]pyridin-2-ylmethyl)-pyrrolidin-3-(S)-yl]-amide;  
 3-(R)-5 Chlorothiophen-2-yl)-ethenesulphonic acid[1-(4-aminoquinolin-7-ylmethyl)-2-oxo-pyrrolidin-3-yl]-amide trifluoroacetate;  
 2-(S)-[[1-(4 Amino-quinolin-7-ylmethyl)-2-oxo-pyrrolidin-3-yl]-(6-chloro-benzo[b]thiophene-2-sulfonyl)-amino]-acetic acid methyl ester, trifluoroacetate;  
 2-(S)-6-Chloro-benzo[b]thiophene-2-sulfonic acid[1-(4-amino-quinolin-7-ylmethyl)-2-oxo-pyrrolidin-3-yl]-amide, trifluoroacetate;  
 2-(s)-(5-Chloro-thiophen-2-yl)-ethenesulfonic acid[1-(4-amino-quinolin-7-ylmethyl)-2-oxo-pyrrolidin-3-yl]-amide, trifluoroacetate;  
 Thieno[3,2-b]pyridine-2-sulfonic acid[1-(4-amino-quinolin-6-ylmethyl)-2-oxo-pyrrolidin-3-(S)-yl]-amide, ditrifluoroacetate:  
 N-(3-Amino-pyridin-4-yl)-2-[3-(7-methoxy-naphthalene-2-sulfonylamino)-2-oxo-pyrrolidin-1-yl]-acetamide;  
 2-[3-(7-Methoxy-naphthalene-2-sulfonylamino)-2-oxo-pyrrolidin-1-yl]-N-pyridin-4-yl-acetamide;  
 6-Chlorobenzo[b]thiophene-2-sulfonic acid{2-oxo-1-[2-(pyridin-4-yl-amino)ethyl]-pyrrolidin-3-(S)-yl}-amide trifluoroacetate;  
 5′-Chloro-[2,2′]bithiophenyl-5-sulfonic acid{2-oxo-1-[2-(pyridin-4-ylamino)-ethyl]-pyrrolidin-3-yl}-amide;  
 6-Chloro-thieno[2,3-b]pyridine-2-sulfonic acid{2-oxo-1-[2-(pyridin-4-ylamino)-ethyl]-pyrrolidin-3-yl}-amide trifluoacetate;  
 Thieno[3,2-b]pyridine-2-sulfonic acid{2-oxo-1-[2-(pyridin-4ylamino)-ethyl]-pyrrolidin-3-yl}-amide ditrifluoroacetate;  
 2-(5-Chloro-thiophen-2-yl)-ethenesulfonic acid{2-oxo-1-[2-(pyridin-4-ylamino)-ethyl]-pyrrolidin-3-yl}-amide;  
 (S)-5′-Chloro-[2,2′]bithiophenyl-5-sulfonic acid{1-[2-(2-amino-3-chloro-pyridin-4-ylamino)-ethyl]-2-oxo-pyrrolidin-3-yl}-amide ditrifluoroacetate;  
 (S)-6Chloro-benzo[b]thiophene-2-sulfonic acid{1-[2-(2-amino-3-chloro-pyridin-4-ylamino)-ethyl]-2-oxo-pyrrolidin-3-yl}-amide ditrifluoroacetate;  
 ((6-Chloro-benzo[b]thiophene-2-sulfonyl)-{2-oxo-1-[2-(pyridin-4-ylamino)-ethyl]-pyrrolidin-3(-yl}-amino)-acetic acid methyl ester;  
 ((6-Chloro-benzo[b]thiophene-2-sulfonyl)-{2-oxo-1-[2-(pyridin-4-ylamino)-ethyl]-pyrrolidin-3-yl}-amino)-acetic acid trifluoroacetate;  
 6-Chloro-benzo[b]thiophene-2-sulfonic acid allyl-{2-oxo-1-[2-(pyridin-4-ylamino)-ethyl]-pyrrolidin-3-yl}-amide;  
 6-Chloro-benzo[b]thiophene-2-sulfonic acid methyl-{2-oxo-1-[2-(pyridin-4-ylamino)-ethyl]-pyrrolidin-3-yl}-amide;  
 (S)-2-(5-Chloro-thiophen-2-yl)-ethenesulfonic acid{1-[2-(2-amino-3-chloro-pyridin-4-ylamino)-ethyl]-2-oxo-pyrrolidin-3-yl}-amide trifluoroacetate;  
 (S)-Thieno[3,2-b]pyridine-2-sulfonic acid{1-[2-(2-amino-3-chloro-pyridin-4-ylamino)-ethyl]-2-oxo-pyrrolidin-3-yl}-amide ditrifluoroacetate;  
 ([2-(5-Chloro-thiophen-2-yl)-ethenesulfonyl]-{2-oxo-1-[2-(pyridin-4-ylamino)-ethyl]-pyrrolidin-3-yl}-amino)-acetic acid methyl ester;  
 ([2-(5-Chloro-thiophen-2-yl)-ethenesulfonyl]-{2-oxo-1-[2-(pyridin-4-ylamino)-ethyl]-pyrrolidin-3-yl}-amino)-acetic acid isopropyl ester;  
 ([2-(5-Chloro-thiophen-2-yl)-ethenesulfonyl]-{2-oxo-1-[2-(pyridin-4-ylamino)-ethyl]-pyrrolidin-3-yl}-amino)-acetic acid trifluoroacetate.  
 2-(5-Chloro-thiophen-2-yl)-ethenesulfonic acid (2-methoxy-ethyl)-{2-oxo-1-[2-(pyridin-4-ylamino)-ethyl]-pyrrolidin-3-yl}-amide trifluoroacetate;  
 ([2-(5-Chloro-thiophen-2-yl)-ethenesulfonyl]-{2-oxo-1-[2-(pyridin-4-ylamino)-ethyl]-pyrrolidin-3-yl}-amino)-acetic acid ethyl ester trifluoroacetate;  
 3-(5-Chloro-thiophen-2-yl)-N-{2-oxo-1-[2-(pyridin-4-ylamino)-ethyl]-pyrrolidin-3-yl}-acrylamide trifluoroacetate;  
 1-[1-(4-Aminoquinazolin-7ylmethyl)-2-oxopyrrolidin-3-(S)-yl]-3-(4-chlorophenyl)urea trifluoroacetate;  
 N-[1-(4-Aminoquinazolin-7-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]-2-(5-chlorothiophen-2-yloxy)acetamide trifluoroacetate;  
 1-(4-Aminoquinazolin-7-ylmethyl)-3-(S)-[(5-chloro-1H-indol-2-ylmethyl)amino]pyrrolidin-2-one trifluoroacetate;  
 1-[(4-Aminoquinazolin-7-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]-3-(5-chlorothiophen-2-yl) urea trifluoroacetate and 5-Chlorothiophene-2-carboxylic acid[1-(4-aminoquinazolin-7-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]amide trifluoroacetate;  
 {[1-(4-Aminoquinazolin-7-ylmethyl2-oxo-pyrrolidin-3-(S)-yl]-[3-(5-chlorothiophen-2-yl)acryloyl]amino}acetic acid methyl ester trifluoroacetate;  
 6-Chlorobenzo[b]thiophene-2-sulfonic acid[1-(4-aminoquinazolin-7-ylmethyl)-2-oxopyrrolidin-3-(R)-yl]amide trifluoroacetate;  
 Thieno[3,2-b]pyridine-2-sulfonic acid[1-(1-aminoisoquinolin -7-ylmethyl)-2-oxopyrrolidin-3-(R)-yl]amide trifluoroacetate;  
 1-(4-Aminoquinolin-7-ylmethyl)-3-(S)-[(5-chloro-1H-indol-2-ylmethyl)amino]pyrrolidin-2-one trifluoroacetate;  
 1-(4-Aminoquinazolin-7-ylmethyl)-3-(S)-[3-(5-chlorothiophen-2-yl)allylamino]pyrrolidin-2-one trifluoroacetate;  
 N-[1-(4-Aminoquinazolin-7-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]-3-(5-chlorothiophen-2-yl)acrylamide trifluoroacetate;  
 1-(4-Aminoquinazolin-7-ylmethyl)-3-(S)-[(5-chloro 1H-benzimidazol-2-ylmethyl)amino]pyrrolidin-2-one trifluoroacetafe;  
 {[1-(4-Aminoquinazolin-7-ylmethyl)-2-oxopyrrolidin-3-(S)-yl][2-(5-chlorothiophen-2-yl)ethenesulfonyl]amino}acetic acid methyl ester trifluoroacetate;  
 {[1-(4-Aminoquinazolin-7-ylmethyl)-2-oxopyrrolidin-3-(S)-yl](5-chloro-1H-indol-2-ylmethyl)amino]acetic acid methyl ester trifluoroacetate;  
 {[1-(4-Aminoquinazolin-7-ylmethyl)-2-oxopyrrolidin-3-(S)-yl][(5-chlorothiophen-2-yl)allyl]amino}acetic acid methyl ester trifluoroacetate;  
 {1-[1-(4-Aminoquinazolin-7-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]-3-(5-chlorothiophen-2-yl)ureido}acetic acid methyl ester trifluoroacetate;  
 N-[1-(4-Aminoquinazolin-7-ylmethyl)-2-oxopyrrolidin-3-(R)-yl]-3-(5-chlorothiophen-2-yl)acrylamide trifluoroacetate;  
 1-(4-Aminoquinazolin-7-ylmethyl)-3-(R)-[(5-chloro-1H-indol-2-ylmethyl)amino]pyrrolidin-2-one trifluoroacetate;  
 1-[1-(4-Aminoquinazolin-7-ylmethyl)-2-oxopyrrolidin-3-(R)-yl]-3-(5-chlorothiophen-2-yl) urea trifluoroacetate and 5-Chlorothiophene-2-carboxylic acid[1-(4-aminoquinazolin-7-ylmethyl)-2-oxopyrrolidin-3-(R)-yl]amide trifluoroacetate;  
 {[1-(4-Aminoquinazolin-7-ylmethyl)-2-oxopyrrolidin-3-(R)-yl](5-chloro-1H-indol-2-ylmethyl)amino]acetic acid methyl ester trifluoroacetate;  
 1-(4-Aminoquinolin-7-ylmethyl)-3-(S)-[(5-chloro-1H-benzimidazol-2-ylmethyl)amino]pyrrolidin-2-one trifluoroacetate;  
 5-Chloro-benzo[b]thiophene-2-sulfonic acid[1-(4-amino-quinazolin-7-ylmethyl)-2-oxo-pyrrolidin-3-(S)-yl]-amide trifluoroacetate;  
 2-(5-Chloro-thiophen-2-yl)-ethenesulfonic acid[1-(4-amino-thieno[3,2-d]pyrimidin-7-ylmethyl)-2-oxo-pyrrolidin-3(S)-yl]-amide;  
 7-Methoxy-naphthalene-2-sulfonic acid[1-(4-amino-quinazolin-7-ylmethyl)-2-oxo-pyrrolidin-3-(S)-yl]-amide trifluoroacetate;  
 2-(5-Chloro-thiophen-2-yl)-ethenesulfonic acid[1-(4-amino-quinazolin-7-ylmethyl)-2-oxo-pyrrolidin-3-(S)-yl]-amide trifluoroacetate;  
 6-Chloro-benzo[b]thiophene-2-sulfonic acid[1- (4-amino-quinazolin-7-ylmethyl)-2-oxo-pyrrolidin-3-(S)-yl]-amide trifluoroacetate;  
 5-Chloro-benzo[b]thiophene-2-sulfonic acid (S)-[1-(4-amino-thieno[3,2-d]pyrimidin-6-ylmethyl)-2-oxo-pyrrolidin-3-yl]-amide trifluoroacetate;  
 Thieno[3,2-b]pyridine-2-sulfonic acid (S)-[1-(4-amino-thieno[3,2-d]pyrimidin-6-ylmethyl)-2-oxo-pyrrolidin-3-yl]-amide trifluoroacetate;  
 6-Chloro-benzo[b]thiophene-2-sulfonic acid (S)-[1-(4-amino-thieno[3,2-d]pyrimidin-6-ylmethyl)-2-oxo-pyrrolidin-3-yl]-amide trifluoroacetate.  
 5′-Chloro-[2,2′]bithiophenyl-5-sulfonic acid (S)-[1-(4-amino-thieno[3,2-d]pyrimidin-6-ylmethyl)-2-oxo-pyrrolidin-3-yl]-amide trifluoroacetate;  
 2-(5-Chloro-thiophen-2-yl)-ethenesulfonic acid (S)-[1-(4-amino-thieno[3,2-d]pyrimidin-6-ylmethyl)-2-oxo-pyrrolidin-3-yl]-amide trifluoroacetate;  
 5-Chloro-benzo[b]thiophene-2-sulfonic acid[(S)-1-(4-amino-thieno[3,2-d]pyrimidin-7-ylmethyl)-2-oxo-pyrrolidin-3-yl]-amide trifluoroacetate;  
 5-Chloro-benzo[b]thiophene-2-sulfonic acid[(S)-1-(4-amino-thieno[2,3-d]pyrimidin-6-ylmethyl)-2-oxo-pyrrolidin-3-yl]-amide trifluoroacetate;  
 5′-Chloro[2,2′]bithiophenyl-5-sulfonic acid[(S)-1-(4-amino-thieno[2,3-d]pyrimidin-6ylmethyl)-2-oxo-pyrrolidin-3-yl]-amide trifluoroacetate;  
 Thieno[3,2-b]pyridine-2-sulfonic acid[(S)-1-(4-amino-thieno[2,3-d]pyrimidin-6-ylmethyl)-2-oxo-pyrrolidin-3-yl]-amide trifluoroacetate;  
 6-Chloro-benzo[b]thiophene-2-sulfonic acid[(S)1-(4-amino-thieno[2,3-d]pyrimidin-6-ylmethyl)-2-oxo-pyrrolidin-3-yl]-amide trifluoroacetate;  
 5′-Chloro-[2,2′]bithiophenyl-5-sulfonic acid[1-(4-amino-thieno[3,2-d]pyrimidin-7-ylmethyl)-2-oxo-pyrrolidin-3-(S)-yl]-amide trifluoroacetate;  
 Thieno[3,2-b]pyridine-2-sulfonic acid[1-(4-amino-thieno[3,2-d]pyrimidin-7-ylmethyl)-2-oxo-pyrrolidin-3-(S)-yl]-amide trifluoroacetate;  
 Chloro-benzo[b]thiophene-2-sulfonic acid[(S)-1-(4-amino-thieno[3,2-d]pyrimidin-7-ylmethyl)-2-oxo-pyrrolidin-3-yl]-amide;  
 6-Chloro-benzo[b]thiophene-2-sulfonic acid[1- (4-aminoquinolin-7-yl methyl)-2-oxo-3(R)-pyrrolidin-3-yl]amide trifluoroacetate; and  
 2-(5-Chlorothiophen-2-yl)-ethenesulfonic acid[1-(4-aminoquinazolin-7-yl methyl)-2-oxopyrrolidin-3-(R)-yl]amide trifluoroacetate.  
 
     
     
         27 . A compound according to  claim 1  which is selected from 
 7-Methoxynaphthalene-2-sulfonic acid[1-(6methoxyisoquinolin-7-ylmethyl)-2-oxopyrrolidin-3-(S)-yl]-amide trifluoroacetate;  
 1-(4-Aminoquinolin-7-ylmethyl)-3-(S)-[(5-chloro-1H-benzimidazol-2-ylmethyl)amino]pyrrolidin-2-one trifluoroacetate:  
 2-(5-Chloro-thiophen-2-yl)-ethenesulfonic acid[2-oxo-1-(1H-pyrrolo[3,2-c]pyridin-2-ylmethyl)-pyrrolidin-3-(S)-yl]-amide;  
 2-(5-Chloro-thiophen-2-yl)-ethenesulfonic acid[1-(4-amino-quinazolin-7-ylmethyl)-2-oxo-pyrrolidin-3-(S)-yl]-amide trifluoroacetate;  
 2-(5-Chloro-thiophen-2-yl)-ethenesulfonic acid (S)-[1-(4-amino-thieno[3,2-d]pyrimidin-6-ylmethyl)-2-oxo-pyrrolidin-3-yl]-amide trifluoroacetate;  
 Thieno[3,2-b]pyridine-2-sulfonic acid[1- (1-aminoisoquinolin-7-ylmethyl)-2-oxopyrrolidin-3-(R)-yl]amide trifluoroacetate:  
 6-Chlorobenzo[b]thiophene-2-sulfonic acid{2-oxo-1-[2-(pyridin-4-yl-amino)ethyl]-pyrrolidin-3-(S)-yl}-amide trifluoroacetate;  
 ((6-Chloro-benzo[b]thiophene-2-sulfonyl)-{2-oxo-1-[2-(pyridin-4-ylamino)-ethyl]-pyrrolidin-3(-yl}-amino)-acetic acid methyl ester;  
 Thieno[3,2-b]pyridine-2-sulfonic acid[2-oxo-1-(1H-pyrrolo[2,3-c]pyridin-2-ylmethyl)-pyrrolidin-3-(S)-yl]-amide ditrifluoroacetate;  
 Thieno[3,2-b]pyridine-2-sulfonic acid[1-(1-amino-isoquinolin-7-ylmethyl)-2-oxo-pyrrolidin-3-(S)-yl]-amide trifluoroacetate;  
 2(S)-(5Chloro-thiophen2-yl)-ethenesulfonic acid[1-(4amino-quinolin-7-ylmethyl)-2-oxo-pyrrolidin-3-(S)-yl]-amide trifluoroacetate;  
 6-Chloro-benzo[b]thiophene-2-sulfonic acid[1-(1,6diamino-isoquinolin-7yl methyl)-2-oxo-pyrrolidin-3-(S)-yl]-amide bistrifluoroacetate;  
 6-Chlorobenzo[b]thiophene-2-sulfonic acid[1-(4-aminoquinolin-7-yl methyl)-2-oxo-3(R)-pyrrolidin-3-yl]amide trifluoroacetate; and  
 2-(5-Chlorothiophen-2-yl)-ethenesulfonic acid[1-(4-aminoquinazolin-7-yl methyl)-2-oxopyrrolidin-3-(R)-yl]amide trifluoroacetate.  
 
     
     
         28 . A compound according to  claim 1  of the formula  
       
         
           
           
               
               
           
         
         wherein  
         
           
             
             
                 
                 
             
           
         
          is a radical selected from the group consisting of  
         
           
             
             
                 
                 
             
           
         
         W is S, O or NR 11 , wherein R 11  is H, alkyl, aralkyl, heteroaralkyl or  
         R 8 (O)C(CH 2 ) q —; A is CH or N; and R 2  is a radical selected from the group consisting of  
         
           
             
             
                 
                 
             
           
         
       
     
     
         29 . A compound according to  claim 1  of the formula  
       
         
           
           
               
               
           
         
         wherein  
         
           
             
             
                 
                 
             
           
         
         R 1  is H; and R 2  is a radical selected from the group consisting of:  
         
           
             
             
                 
                 
             
           
         
         R 1  is H; and R 2  is a radical selected from the group consisting of:  
         
           
             
             
                 
                 
             
           
         
         R 1  is H; and R 2  a radical selected from the group consisting of:  
         
           
             
             
                 
                 
             
           
         
         R 1  is H; and R 2  is a radical selected from the group consisting of:  
         
           
             
             
                 
                 
             
           
         
       
     
     
         30 . A pharmaceutical composition comprising a pharmaceutically acceptable amount of a compound according to  claim 1  and a pharmaceutically acceptable carrier.  
     
     
         31 . A method for treating a patient suffering from a physiological disorder capable of being modulated by inhibiting an activity of Factor Xa comprising administering to the patient a therapeutically effective amount of a compound according to  claim 1 .  
     
     
         32 . The method according to  claim 31  wherein the physiological disorder is abnormal thrombus formation, acute myocardial infarction, unstable angina, thromboembolism, acute vessel closure associated with thrombolytic therapy or percutaneous transluminal coronary angioplasty, transient ischemic attacks, stroke, pathologic thrombus formation occurring in the veins of the lower extremities following abdominal, knee and hip surgery, a risk of pulmonary thromboembolism, or disseminated systemic intravascular coagulopathy occurring in vascular systems during septic shock, certain viral infections or cancer.  
     
     
         33 . The method according to  claim 31  wherein the physiological disorder is abnormal thrombus formation, acute myocardial infarction, unstable angina, thromboembolism, acute vessel closure associated with thrombolytic therapy, transient ischemic attacks, restenosis post coronary or venous angioplasty, pathologic thrombus formation occurring in the veins of the lower extremities following abdominal, knee and hip surgery or a risk of pulmonary thromboembolism.  
     
     
         34 . The method according to  claim 31  wherein the physiological disorder is stroke, vessel luminal narrowing, or disseminated systemic intravascular coagulopathy occurring in vascular systems during septic shock, certain viral infections or cancer.  
     
     
         35 . The method of  claim 31  wherein said compound according to  claim 1  is administered in combination with at least one other agent selected from diagnostic agents, cardioprotective agents, direct thrombin inhibiting agents, anticoagulant agents, antiplatelet agents and fibrinoloytic agents.  
     
     
         36 . The method of  claim 35  wherein said other agent is selected from standard heparin, low molecular weight heparin, direct thrombin inhibitors, aspirin, fibrinogen receptor antagonists, streptokinase, urokinase and tissue plasminogen activator.  
     
     
         37 . The method of  claim 36  wherein said other agent is selected from direct thrombin inhibitors and fibrinogen receptor antagonists.  
     
     
         38 . The method of  claim 37  wherein said thrombin inhibitor is selected from boroarginine derivatives, boropeptides, hirudin, argatroban and the pharmaceutically acceptable salts, prodrugs, derivatives and analogs thereof.  
     
     
         39 . The pharmaceutical composition of  claim 30  further comprising at least one other agent selected from diagnostic agents, cardioprotective agents, direct thrombin inhibiting agents, anticoagulant agents, antiplatelet agents and fibrinoloytic agents.  
     
     
         40 . The pharmaceutical composition of  claim 39  wherein said other agent is selected from standard heparin, low molecular weight heparin, direct thrombin inhibitors, aspirin, fibrinogen receptor antagonists, streptokinase, urokinase and tissue plasminogen activator.  
     
     
         41 . The pharmaceutical composition of  claim 40  wherein said other agent is selected from direct thrombin inhibitors and fibrinogen receptor antagonists.  
     
     
         42 . A kit for treating a patient suffering from a physiological disorder capable of being modulated by inhibiting an activity of Factor Xa, said kit comprising a plurality of separate containers, wherein at least one of said containers contains a compound according to  claim 1  and at least one other of said containers contains at least one other agent selected from diagnostic agents, cardioprotective agents, direct thrombin inhibiting agents, anticoagulant agents, antiplatelet agents and fibrinoloytic agents, each of said containers optionally further containing a pharmaceutically acceptable carrier.