Diaminopropionic acid derivatives

Abstract

A compound of formula 1a which is useful for treating reperfusion injury, and salts, prodrugs, and related compounds.

What is claimed is:  
     
         1 . A compound of formula:  
       
         
           
           
               
               
           
         
       
       wherein R 1  is a group of the formula  
       
         
           
           
               
               
           
         
         where A is hydrogen, hydroxy, amino, or halogen and B is amino, carboxy, hydrogen, hydroxy, cyano, trifluoromethyl, halogen, lower alkyl, or lower alkoxy; R 2  is a group of the formula  
         
           
             
             
                 
                 
             
           
         
          where R 3  is hydrogen, carboxy, or lower alkyl;  
         n is 0 or 1;  
         U, V, and W are independently hydrogen, halogen, or lower alkyl provided U and  
         V are not both hydrogen;  
         X is carbonyl, phenyl-substituted loweralkylene, or sulfonyl;  
         Y is lower alkylene which may be substituted with one or more of amino, substituted amino, lower alkyl, or cyclo lower alkyl, or y is lower alkenylene or lower alkylenethio; and k is 0 or 1; when k is 1:  
         Z is hydrogen, lower alkylthio, —COOH, —CONH 2 , or amino, or when k is 0 or 1, Z is: 1-adamantyl, diphenylmethyl, 3-[[(5-chloropyridin-2-yl)amino]carbonyl]pyrazin-2-yl, hydroxy, phenylmethoxy, 2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]phenyl, [(2,6-dichlorophenyl)methoxy]phenyl, or Z is one of the following: 
 cycloalkyl or aryl containing 0 to 3 heteroatoms which may be the same or different, or a fused ring system containing two or three rings which rings are independently cycloalkyl or aryl containing 0 to 3 heteroatoms which may be the same or different, any of which rings may be unsubstituted, or substituted with at least one of: 
 halogen, cyano, amino, substituted amino, aminosulfonyl, nitro, oxo, hydroxy, aryl, aryloxy, unsubstituted lower alkyl, halogen-substituted lower alkyl, lower alkoxy-substituted lower alkyl, lower alkoxy, lower alkanesulfonyl, lower alkylthio, acetyl, aminocarbonyl, hydrazino, carboxy, lower alkoxycarbonyl, acetoxy or amino loweralkyl;  
 or a pharmaceutically acceptable salts and esters thereof.  
 
 
       
     
     
         2 . A compound of  claim 1  having formula  
       
         
           
           
               
               
           
         
         wherein U is chlorine or bromine; X is carbonyl, phenyl-substituted loweralkylene, or sulfonyl;  
         Y is lower alkylene which may be substituted by one or more of amino, lower alkyl, substituted amino, or cyclo-lower alkyl, or Y is lower alkenylene, or lower alkylenethio, and k is 0 or 1; when k is 1,  
         Z is: hydrogen, lower alkylthio, —COOH, —CONH 2 , or amino, or when k is 0 or 1, Z is: 1-adamantyl, diphenylmethyl, 3-[[(5-chloropyridin-2-yl)amino]carbonyl]pyrazin-2-yl, hydroxy, or phenylmethoxy, or Z is one of the following: 
 cycloalkyl or aryl containing 0 to 3 heteroatoms which may be the same or different, or a fused ring system containing two or three rings which rings are independently cycloalkyl or aryl containing 0 to 3 heteroatoms which may be the same or different, any of which rings may be unsubstituted, or substituted with at least one of: 
 halogen, cyano, amino, substituted amino, aminosulfonyl, nitro, oxo, hydroxy, aryl, aryloxy, unsubstituted lower alkyl, halogen-substituted lower alkyl, lower alkoxy-substituted lower alkyl, lower alkoxy, lower alkanesulfonyl, lower alkylthio, acetyl, aminocarbonyl, hydrazino, carboxy, lower alkoxycarbonyl, or acetoxy.  
 
 
       
     
     
         3 . A compound of  claim 2  wherein X is carbonyl, k is 0; and Z is thiophene.  
     
     
         4 . A compound of  claim 1  having the formula  
       
         
           
           
               
               
           
         
         wherein U is chlorine or bromine; X is carbonyl, phenyl-substituted loweralkylene, or sulfonyl;  
         Y is lower alkylene which may be substituted by one or more of amino, lower alkyl, substituted amino, or cyclo-lower alkyl, or Y is lower alkenylene or lower alkylenethio, and k is 0 or 1; when k is 1, Z is:  
         hydrogen, lower alkylthio, —COOH, —CONH 2 , or amino, or when k is 0 or 1, Z is: 1-adamantyl, diphenylmethyl, 3-[[(5-chloropyridin-2-yl)amino]carbonyl]pyrazin-2-yl, or Z is one of the following: 
 cycloalkyl or aryl containing 0 to 3 heteroatoms which may be the same or different, or a fused ring system containing two or three rings which rings are independently cycloalkyl or aryl containing 0 to 3 heteroatoms which may be the same or different, any of which rings may be unsubstituted, or substituted with at least one of: 
 halogen, cyano, amino, substituted amino, aminosulfonyl, nitro, oxo, hydroxy, aryl, aryloxy, unsubstituted lower alkyl, halogen-substituted lower alkyl, lower alkoxy-substituted lower alkyl, lower alkoxy, lower alkanesulfonyl, lower alkylthio, acetyl, aminocarbonyl, hydrazino, carboxy, lower alkoxycarbonyl, or acetoxy.  
 
 
       
     
     
         5 . A compound of  claim 4  wherein X is carbonyl; k is 0; and Z is thiophene or phenyl.  
     
     
         6 . A compound of  claim 5  wherein Z is thiophene.  
     
     
         7 . A compound of  claim 1  wherein Z is thiophene, furan, thiazole, cyclopentyl, cyclohexyl, piperidine, pyridine, naphthalene, benzothiophene, benzothiazole, 1,4-dioxa-8-thiaspiro[4,5]decyl, phenyl, or phenyl substituted by one or more of lower alkoxy, lower alkyl, chlorine, bromine, fluorine, hydroxy, nitro, cyano, amino, substituted amino, aminosulfonyl, alkoxycarbonyl, trifluoromethyl, or carboxy.  
     
     
         8 . A compound of  claim 7  wherein R 1  is a group of formula  
       
         
           
           
               
               
           
         
       
       or R 1  is a group of the formula  
       
         
           
           
               
               
           
         
       
       R 2  is a group of the formula  
       
         
           
           
               
               
           
         
       
       W is hydrogen and one of U or V is chlorine or bromine while the other is hydrogen or one of U or V is methyl and the other is chlorine or bromine; X is carbonyl; and Y is lower alkylene substituted with cycloalkyl, lower alkylthio, unbranched lower alkyl or alkenyl or k is 0.  
     
     
         9 . A compound of  claim 1  wherein A, when present, is hydroxy, hydrogen, or amino and B is hydrogen or hydroxy; W is hydrogen and at least one of U and V are methyl or halogen, k is 0 or Y is lower alkylene; and Z is hydrogen, phenyl, thiophene, furan, pyrrole, pyrazole, imidazole, thiazole, or isoxazole or a six-membered aromatic ring with one to three nitrogens any of which may be unsubstituted or substituted with at least one of: 
 halogen, hydroxy, lower alkoxy, nitro, amino, substituted amino, cyano, carboxy, trifluoromethyl, lower alkyl, aminosulfonyl, or lower alkoxycarbonyl.  
 
     
     
         10 . Compounds of  claim 9  which are: 
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(phenylsulfonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(phenylmethyl)amino-L-alanine;  
 3-[(3-carboxybenzoyl)amino-N-[2-chloro-4-[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine;  
 N-[4-[[[(3-aminophenyl)methylamino]carbonyl]-2-bromobenzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine;  
 3-(benzoylamino)-N-[2-chloro-4-[[[(3,5-dihydroxybenzoyl)amino]methyl]benzoyl]-L-alanine;  
 3-(benzoylamino)-N-[2-chloro-4-[[[(2-hydroxybenzoyl)amino]methyl]benzoyl]-L-alanine;  
 3-(benzoylamino)-N-[2-chloro-4-[[[(3-hydroxybenzoyl)amino]methyl]benzoyl]-L-alanine;  
 N-[4-[[[(3-aminobenzoyl)amino]methyl]-2-chlorobenzoyl]-3-(benzoylamino)-L-alanine;  
 N-[2-bromo-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine;  
 N-[2-fluoro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine; and  
 N-[2-chloro-4-[[[(3,5-dihydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[thiophene-2-carbonyl]amino-L-alanine.  
 
     
     
         11 . A compound of  claim 9  wherein X is carbonyl.  
     
     
         12 . Compounds of  claim 11  which are: 
 N-[2-chloro-4-[5-[(3-hydroxy)phenylmethylamino]tetrazol-1-yl]benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[1-oxo-3-(3-hydroxyphenyl)propyl]benzoyl]-3-(thioiphene-2-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[1-hydroxy-3-(3-hydroxyphenyl)propyl]benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine; and  
 N-[2-chloro-4-(1-oxo-3-phenylpropyl)benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine.  
 
     
     
         13 . A compound of  claim 11  wherein R 1  is a group of the formula  
       
         
           
           
               
               
           
         
       
     
     
         14 . A compound of  claim 13  wherein A and B are hydrogen.  
     
     
         15 . A compound of  claim 14  wherein U is bromine or chlorine.  
     
     
         16 . A compound of  claim 15  wherein k is 0.  
     
     
         17 . A compound of  claim 15  wherein Y is methylene.  
     
     
         18 . A compound of  claim 16  wherein Z is phenyl or thiophene or phenyl or thiophene substituted by at least one of lower alkyl, lower alkoxy, hydroxy, halogen, carboxy, nitro, aminosulfonyl, cyano, or lower alkoxy carbonyl.  
     
     
         19 . Compounds of  claim 18  which are: 
 N-[2-chloro-4-[(2-phenyl-trans-cyclopropyl)carbonyl]benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-(phenoxyacetyl)benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine; and  
 N-[2-chloro-4-(3-phenyl-1-propenyl)benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine.  
 
     
     
         20 . A compound of  claim 1  having the formula  
       
         
           
           
               
               
           
         
         wherein U is chlorine, bromine, fluorine, or methyl; R 3  is hydrogen, carboxy, or lower alkyl;  
         X is carbonyl, phenyl-substituted loweralkylene, or sulfonyl;  
         Y is lower alkylene which may be substituted by one or more of amino, substituted amino, loweralkyl, or cyclo lower alkyl, or Y is lower alkenylene or lower alkylenethio, k is 0 or 1; when k is 1, Z is hydrogen, lower alkylthio, —COOH, —CONH 2 , or amino, or when k is 0 or 1, Z is: 1-adamantyl, diphenylmethyl,3-[[(5-chloropyridin-2-yl)amino]carbonyl]pyrazin-2-yl, hydroxy, phenylmethoxy, 2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]phenyl, [(2,6-dichlorophenyl)methoxy]phenyl or Z is one of the following: 
 cycloalkyl or aryl containing 0 to 3 heteroatoms which may be the same or different, or a fused ring system containing two or three rings which rings are independently cycloalkyl or aryl containing 0 to 3 heteroatoms which may be the same or different, any of which rings may be unsubstituted, or substituted with at least one of: 
 halogen, cyano, amino, substituted amino, aminosulfonyl, nitro, oxo, hydroxy, aryl, aryloxy, unsubstituted lower alkyl, halogen-substituted lower alkyl, lower alkoxy-substituted lower alkyl, lower alkoxy, lower alkanesulfonyl, lower alkylthio, acetyl, aminocarbonyl, hydrazino, carboxy, lower alkoxycarbonyl, acetoxy, or amino loweralkyl.  
 
 
       
     
     
         21 . A compound of  claim 20  which is 3-(11-aminoundecanoyl)amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-(L-alanine.  
     
     
         22 . A compound of  claim 20  which has formula  
       
         
           
           
               
               
           
         
         wherein Z is 1-adamantyl, diphenylmethyl, 3-[[(5-chloropyridin-2-yl)amino]carbonyl]pyrazin-2-yl,2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]phenyl, [(2,6-dichlorophenyl)methoxy]phenyl or Z is one of the following: 
 cycloalkyl or aryl containing 0 to 3 heteroatoms which may be the same or different, or a fused ring system containing two or three rings which rings are independently cycloalkyl or aryl containing 0 to 3 heteroatoms which may be the same or different, any of which rings may be unsubstituted, or substituted with at least one of: 
 halogen, cyano, amino, substituted amino, aminosulfonyl, nitro, oxo, hydroxy, aryl, aryloxy, unsubstituted lower alkyl, halogen-substituted lower alkyl, lower alkoxy-substituted lower alkyl, lower alkoxy, lower alkanesulfonyl, lower alkylthio, acetyl, aminocarbonyl, hydrazino, carboxy, lower alkoxycarbonyl, acetoxy, or aminomethyl.  
 
 
       
     
     
         23 . A compound of  claim 22  wherein Z is cycloalkyl.  
     
     
         24 . Compounds of  claim 23  which are N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(cyclopropylcarbonyl)amino-L-alanine; 
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[(2, 2-dichloro-1-methylcyclopropyl) carbonyl]amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[(1-phenylcyclopropyl)carbonyl]amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(cyclobutylcarbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(cyclopentylcarbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[1-( 2-methoxyethyl)cyclopentylcarbonyl]amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[(1-phenylcyclopentyl)carbonyl]amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(cyclohexylcarbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(1-methylcyclohexylcarbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[1-aminocyclopentyl)carbonyl]amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[cis-4-aminocyclohexyl)carbonyl]amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[trans-6-amino-3-cyclohexene-1-carbonyl]amino-L-alanine;  
 3-[[trans-4-(aminomethyl)cyclohexyl]carbonyl]amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine;  
 3-[(1-aminocyclohexyl)carbonyl]amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine; and  
 3-[(3-aminocyclohexyl)carbonyl]amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine.  
 
     
     
         25 . Compounds of  claim 22  which are: 
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(diphenylacetyl)amino-L-alanine;  
 3-(1-adamantylcarbonyl)amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[(2S)-5-oxotetrahydrofuran-2-carbonyl]amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(1,4-dioxa-8-thiaspiro[4.5]decane-6-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(2-phenoxybenzoyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(furan-2-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(5-nitrofuran-2-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(5-bromofuran-2-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[(3,5-dimethylisoxazol-4-yl)carbonyl]amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(piperidine-4-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(L-prolyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(1,2,3-thiadiazol-4-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(4-methyl-1,2,3-thiadiazol-5-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(isoxazole-5-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(4-chloro-2-nitrobenzoyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(2,4-dimethylthiazole-5-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]amino]-L-alanine; and  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[[[(3S)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-3-yl]carbonyl]amino]-L-alanine.  
 
     
     
         26 . A compound of  claim 22  wherein Z is thiophene, or Z is phenyl, or Z is thiophene substituted with at least one of halogen or methyl, or Z is phenyl substituted with at least one of halogen, hydroxy, cyano, lower alkyl, lower alkoxy, amino, substituted amino, aminocarbonyl, nitro, aminosulfonyl, acetoxy, or substituted lower alkyl, or Z is a five- or six-membered ring with 0 to 3 heteroatoms selected from O, N, and S which may be the same or different, which ring may be unsubstituted or substituted with hydroxy, or Z is a fused ring system containing at least one benzene ring and containing one or two other rings which are independently 5 or 6-membered cycloalkyl or aryl with 0 to 3 heteroatoms selected from O, N, and S which may be the same or different, any of which may be unsubstituted or substituted with at least one of lower alkoxy, halogen, oxo, or hydroxy.  
     
     
         27 . Compounds of  claim 26  which are 
 3-(3-amino-5-nitrobenzoyl)amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine;  
 3-(3-bromo-5-nitrobenzoyl)amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3-nitro-5-trifluoromethylbenzoyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3-methyl-5-nitrobenzoyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3-methyl-4-nitrobenzoyl)amino-L-alanine;  
 3-(4-amino-3-methylbenzoyl)amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine;  
 3-(4-bromo-3-methylbenzoyl)amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3-methoxy-4-nitrobenzoyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3-hydroxy-4-methoxybenzoyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(2-methyl-3-nitrobenzoyl)amino-L-alanine;  
 3-(1H-benzotriazole-5-carbonyl)amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine;  
 3-(3-aminocarbonylbenzoyl)amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(furan-3-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3-fluoro-5-trifluoromethylbenzoyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[(4R)-thiazolidine-4-carbonyl]amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[(4R)-4-hydroxy-L-prolyl]amino-L-alanine; and  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[2,3-dihydro-1H-indole-2-carbonyl]amino-L-alanine.  
 
     
     
         28 . A compound of  claim 26  wherein Z is thiophene, or thiophene substituted with at least one of halogen or methyl.  
     
     
         29 . Compounds of  claim 28  which are: 
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[(thiophene-2-carbonyl)amino]-L-alanine;  
 3-(3-bromothiophene-2-carbonyl)amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine;  
 3-(5-bromothiophene-2-carbonyl)amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3-chlorothiophene-2-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(5-chlorothiophene-2-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(4,5-dibromothiophene-2-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3-methylthiophene-2-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(5-methylthiophene-2-carbonyl)amino-L-alanine; and  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(thiophene-3-carbonyl)amino-L-alanine.  
 
     
     
         30 . A compound of  claim 26  wherein Z is a five- or six-membered ring with one to three nitrogens.  
     
     
         31 . Compounds of  claim 30  which are: 
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(pyrrole-2-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(5-nitropyrazole-3-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(pyridine-2-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(6-methylpyridine-2-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[5-(3,4-dibromobutyl)pyridine-2-carbonyl]amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(pyridine-3-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(2-chloropyridine-3-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(6-chloropyridine-3-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(2,6-dimethoxypyridine-3-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(2-hydroxypyridine-3-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(pyrazine-2-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[3-[[(5-chloro-2-pyridinyl)amino]carbonyl]pyrazine-2-carbonyl]amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(2,4-dihydroxypyrimidine-5-carbonyl)amino-L-alanine; and  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(2,4-dihydroxypyrimidine-6-carbonyl)amino-L-alanine.  
 
     
     
         32 . A compound of  claim 26  wherein Z is phenyl, or phenyl substituted with at least one of hydroxy, cyano, lower alkyl or substituted lower alkyl.  
     
     
         33 . Compounds of  claim 32  which are: 
 3-benzoylamino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3-cyanobenzoyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3-hydroxybenzoyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(2-methylbenzoyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3-methylbenzoyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(4-methylbenzoyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[3-(trifluoromethyl)benzoyl]amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3,5-dimethylbenzoyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3,4-dimethylbenzoyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3-hydroxy-4-methylbenzoyl)amino-L-alanine; and  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(2-hydroxy-4-methylbenzoyl)amino-L-alanine.  
 
     
     
         34 . A compound of  claim 26  wherein Z is phenyl substituted with at least one hydroxy.  
     
     
         35 . Compounds of  claim 34  which are 
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3-hydroxybenzoyl)amino-L-alanine; and  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3,5-dihydroxybenzoyl)amino-L-alanine.  
 
     
     
         36 . A compound of  claim 35  which is N-[2-chloro-4-[[[(3-hydroxyphenyl) methyl]amino]carbonyl]benzoyl]-3-(3-hydroxybenzoyl)amino-L-alanine.  
     
     
         37 . A compound of  claim 35  which is N-[2-chloro-4-[[[(3-hydroxyphenyl) methyl]amino]carbonyl]benzoyl]-3-(3,5-dihydroxybenzoyl)amino-L-alanine.  
     
     
         38 . A compound of  claim 26  wherein Z is phenyl substituted with at least one of lower alkoxy, lower alkoxy carbonyl, —O—C(O)—CH 3 , or —C(O)—O—CH 3.    
     
     
         39 . Compounds of  claim 38  which are: 
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3-methoxybenzoyl)amino-L-alanine;  
 3-(2-acetoxybenzoyl)amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(4-ethoxybenzoyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(2-methoxybenzoyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(4-methoxybenzoyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[3-(methoxycarbonyl)benzoyl]amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(4-pentyloxybenzoyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3,4,5-trimethoxybenzoyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3,5-dimethoxybenzoyl)amino-L-alanine; and  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3,4-dimethoxybenzoyl)amino-L-alanine.  
 
     
     
         40 . A compound of  claim 26  wherein Z is phenyl substituted with at least one halogen.  
     
     
         41 . Compounds of  claim 40  which are: 
 3-(2-bromobenzoyl)amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine;  
 3-(3-bromobenzoyl)amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine; 3-(2-chlorobenzoyl)amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine; 3-(3-chlorobenzoyl)amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine; 3-(4-chlorobenzoyl)amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3-fluorobenzoyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3-iodobenzoyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(2,4,5-trifluorobenzoyl)amino-L-alanine;  
 3-(3-chloro-5-fluorobenzoyl)amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3,5-dichlorobenzoyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3,5-dibromobenzoyl)amino-L-alanine; and  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3,5-difluorobenzoyl)amino-L-alanine.  
 
     
     
         42 . A compound of  claim 26  wherein Z is phenyl substituted with at least one of amino, substituted amino, nitro, or aminosulfonyl.  
     
     
         43 . Compounds of  claim 42  which are: 
 3-(3-aminobenzoyl)amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine;  
 3-(4-aminosulfonylbenzoyl)amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3-dimethylaminobenzoyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(4-dimethylaminobenzoyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3,5-dinitrobenzoyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(2-nitrobenzoyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3-nitrobenzoyl)amino-L-alanine; and  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(4-nitrobenzoyl)amino-L-alanine.  
 
     
     
         44 . A compound of  claim 26  wherein Z is a fused ring system containing at least one benzene ring and containing one or two other rings which are independently 5 or 6-membered cycloalkyl or aryl with 0 to 2 heteroatoms selected from O, N, and S which may be the same or different, any of which may be unsubstituted or substituted with at least one of lower alkoxy, halogen, oxo, or hydroxy.  
     
     
         45 . Compounds of  claim 44  which are: 
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[(1,2,3,4-tetrahydronaphthalene-2-carbonyl)amino]-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[(DL-7-methoxy-1,2,3,4,4aβ,9,10,10aβ-octahydro-2β-phenanthrenecarbonyl)amino]-L-alanine;  
 3-[(6-bromo-2-oxo-1,2,3,4-tetrahydroquinoline-4-carbonyl)amino]-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[benzofuran-2-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(benzothiophene-2-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(benzimidazole-5-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(benzothiazole-6-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(naphthalene-1-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(naphthalene-2-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(isoquinoline-1-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(quinoline-2-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(4-methoxyquinoline-2-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(quinoline-3-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(quinoline-4-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(cinnoline-4-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(2-hydroxyquinoxaline-3-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(4-oxo-4H-1-benzopyran-2-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(2-oxo-2H-1-benzopyran-3-carbonyl)amino-L-alanine;  
 3-(anthracene-9-carbonyl)amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(1,2,3,4-tetrahydroacridine-9-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(2-methoxy-11-oxo-11H-pyrido[2,1 ]quinazoline-8-carbonyl)amino-L-alanine; and  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(9-oxo-9H-thioxanthene-3-carbonyl)amino-L-alanine.  
 
     
     
         46 . A compound of  claim 20  which has formula  
       
         
           
           
               
               
           
         
         wherein Y is lower alkylene which may be substituted by one or more of ami no, substituted amino, loweralkyl, or cyclo lower alkyl, or Y is lower alkenylene or lower alkylenethio; k is 1;  
         Z is hydrogen, lower alkylthio, —COOH, —CONH 2 , amino, 1-adamantyl, diphenylmethyl, 3-[[(5-chloropyridin-2-yl)amino]carbonyl]pyrazin-2-yl, 2-chlor o-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]phenyl, [(2,6-dichlorophenyl)-methoxy]phenyl, phenylmethoxy, hydroxy or Z is one of the following: 
 cycloalkyl or aryl containing 0 to 3 heteroatoms which may be the same or different, or a fused ring system containing two or three rings which rings are independently cycloalkyl or aryl containing 0 to 3 heteroatoms which may be the same or different, any of which rings may be unsubstituted, or substituted with at least one of:  
 
         halogen, cyano, amino, substituted amino, aminosulfonyl, nitro, oxo, hydroxy, aryl, aryloxy, unsubstituted lower alkyl, halogen-substituted lower alkyl, lower alkoxy-substituted lower alkyl, lo er alkoxy, lower alkanesulfonyl, lower alkylthio, acetyl, aminocaronyl, hydrazino, carboxy, lower alkoxycarbonyl, or acetoxy.  
       
     
     
         47 . A compound of  claim 46  wherein Y is methylene.  
     
     
         48 . Compounds of  claim 47  which are: 
 3-acetylamino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(cyclopentylacetyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(cyclohexylacetyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(phenylacetyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(4-methoxyphenylacetyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(4-nitrophenylacetyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3-trifluoromethylphenylacetyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3,5-dinitrophenylacetyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(2-thienylacetyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3-pyridylacetyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(2-naphthylacetyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(9H-fluoren-9-ylacetyl)amino-L-alanine;  
 3-[[(2S)-2-carboxy-2-[2-chloro-4-[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoylamino]ethylaminocarbonyl] methyl]benzothiazol-3-ium salt;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[3-amino-2-oxo-1(2H)-pyridineacetyl]amino-L-alanine;  
 3-(3-aminohexahydro-2-oxo-1H-azepine-1-acetyl)amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine; and  
 3-(4-amino-1,3,4,5-tetrahydro-3-oxo-2H-2-benzazepine-2-acetyl)amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine.  
 
     
     
         49 . A compound of  claim 46  wherein Y is —CH 2 CH 2 —, —C(CH 3 ) 2 CH 2 —, —CH(CH 3 )CH 2 , —CH 2 CH(CH 3 )CH 2 —, —CH 2 CH(CH 3 )—, or  
       
         
           
           
               
               
           
         
       
     
     
         50 . Compounds of  claim 49  which are: 
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3-phenylpropanoyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3,5-dimethylisoxazol-4-yl)propanoyl]amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[3-(piperidin-1-yl)propanoyl]amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[(3RS)-3-phenylbutanoyl]-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[3-cyclohexyl-(2S)-2-(1-pyrrolyl)propanoyl]amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(trimethylacetyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(2-methylpropanoyl)amino-L-alanine; and  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(3-methylbutanoyl)amino-L-alanine.  
 
     
     
         51 . A compound of  claim 46  wherein Y is —CH═CH—, —CH═CH—CH 2 —, or —CH 2 S—.  
     
     
         52 . Compounds of  claim 51  which are: 
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3 (4-pyridylthioacetyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3 (pyrimidin-2-ylthio)acetylamino-L-alanine; 3-(but-2-enoyl)amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[3-(4-methoxyphenyl)prop-2-enoyl]amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[3-(pyridin-3-yl)prop-2-enoyl]amino-L-alanine; and  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-3-( 2-thienyl)prop-2-enoyl]amino-L-alanine.  
 
     
     
         53 . A compound of  claim 46  wherein Y is lower alkylene substituted by amino, lower alkyl, lower alkylamino, or trifluoromethyl.  
     
     
         54 . Compounds of  claim 53  which are: 
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(L-methionyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(L-lysyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(L-phenylalanyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(L-asparaginyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(L-tryptophyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(L-β-glutamyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(N-methyl-L-alanyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(N-methylglycyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(L-leucyl)amino-L-alanine;  
 3-(2-amino-2-methylpropanoyl)amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine;  
 3-(3-amino-4,4,4-trifluorobutanoyl)amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine;  
 3-(3-amino-2-methylpropanoyl)amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[4-(2,6-dichlorophenyl)methoxy-L-phenylalanyl]amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(L-seryl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-[O-(phenylmethyl)-L-seryl]amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(L-phenylglycyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(4-nitro-L-phenylalanyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(4-fluoro-D,L-phenylalanyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(D-tyrosyl)amino-L-alanine;  
 3-(D-aspartyl)amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(D-tryptophyl)amino-L-alanine;  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(L-alanyl)amino-L-alanine; and  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(D-alanyl)amino-L-alanine.  
 
     
     
         55 . A compound of  claim 46  wherein Y is —CH 2 CH 2 CH 2-.  
     
     
         56 . Compounds of  claim 55  which are: 
 3-(4-aminobutanoyl)amino-N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-L-alanine; and  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(4-carboxy-1-oxobutyl)amino-L-alanine.  
 
     
     
         57 . A compound of  claim 20  wherein X is carbonyl; k is 0; and Z is thiophene or phenyl, or thiophene or phenyl substituted by one or more of lower alkyl, lower alkoxy, hydroxy, halogen, carboxy, nitro, aminosulfonyl, cyano, or lower alkoxy carbonyl.  
     
     
         58 . A compound of  claim 57  wherein Z is thiophene or phenyl, or thiophene or phenyl substituted by methyl, methoxy, chlorine, bromine, fluorine, hydroxy, or nitro.  
     
     
         59 . Compounds of  claim 58  which are: 
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(4-methoxythiophene-3-carbonyl)amino-L-alanine; and  
 N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-5-chloro-4-methoxythiophene-3-carbonyl)amino-L-alanine.  
 
     
     
         60 . A compound of  claim 1  having formula  
       
         
           
           
               
               
           
         
       
       wherein R 1  is a group of the formula  
       
         
           
           
               
               
           
         
       
       at least one of U and V are chlorine, bromine, or methyl; k is 0 or Y is butylene; X is carbonyl, phenyl-substituted lower alkylene, or sulfonyl; and Z is hydrogen, phenyl, thiazole, orthiophene, or Z is phenyl, thiazole, or thiophene substituted with at least one of methyl or acetylamino.  
     
     
         61 . A compound of  claim 60  wherein R 3  is hydrogen.  
     
     
         62 . Compounds of  claim 61  which are: 
 3-(benzoylamino)-N-[2-chloro-4-[[(2,3-dihydro-2-oxo-1H-indol-4-ylmethyl)aminocarbonyl]benzoyl]-(L-alanine;  
 3-(benzoylamino)-N-[2-chloro-4-[[(1H-indol-4-ylmethyl)aminocarbonyl]benzoyl]-L-alanine;  
 N-[2-chloro-4-[[(1H-benzimidazol-4-ylmethyl)aminocarbonyl]benzoyl]3-(thiophene-2-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[(1H-indol-4-ylmethyl)aminocarbonyl]benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[(2,3-dihydro-1H-indol-4-ylmethyl)aminocarbonyl]benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine;  
 N-[2-bromo-4-[[(1H-indol-4-ylmethyl)amino]carbonyl]benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[(1H-indol-4-ylmethyl)amino]carbonyl]benzoyl]-3-(thiophene-3-carbonyl)amino-L-alanine;  
 N-[2-chloro-4-[[(1H-indol-4-ylmethyl)amino]carbonyl]benzoyl]-3-(5-methylthiophene-2-carbonyl)amino-L-alanine; and  
 N-[2-chloro-4-[[[(1H-indazol-4-yl)methyl]amino]carbonyl]benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine.  
 
     
     
         63 . A compound of  claim 60  wherein R 3  is methyl.  
     
     
         64 . Compounds of  claim 63  which are: 
 3-(1-butanesulfonylamino)-N-[2-chloro-4-[[[(1R)-1-(1-naphthalenyl)ethyl]amino]carbonyl]benzoyl]-L-alanine;  
 3-[(2-acetamido-4-methylthiazol-5-yl)sulfonyl]amino-N-[2-chloro-4-[[[(1R)-1-(1-naphthalenyl)ethyl]amino]carbonyl]benzoyl]-L-alanine;  
 N-[2,6-dimethyl-4-[[[(1R)-1-(1-naphthalenyl)ethyl]amino]carbonyl]benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine;  
 N-[2-bromo-4-[[[(1R)-1-(1-naphthalenyl)ethyl]amino]carbonyl]benzoyl]-3-(thiophene-2-carbonyl)amino-L-alanine;  
 N-[2,6-dichloro-4-[[[(1R)-1-(1-naphthalenyl)ethyl]amino]carbonyl]benzoyl]-3-[(thiophene-2-carbonyl)amino]-L-alanine;  
 N-[2-methyl-4-[[[(1R)-1-(1-naphthalenyl)ethyl]amino]carbonyl]benzoyl -3-[(thiophene-2-carbonyl)amino]-L-alanine;  
 3-(benzoylamino)-N-[2-methyl-4-[[[(1R)-1-(1-naphthalenyl)ethyl]amino]carbonyl]benzoyl]-L-alanine; and  
 3-(benzoylamino)-N-[2,6-dichloro-4-[[[(1R)-1-(1-naphthalenyl)ethyl]amino]carbonyl]benzoyl]-L-alanine.  
 
     
     
         65 . A compound of  claim 64  which is N-[2,6-dichloro-4-[[[(l R)-l-(1-naphthalenyl)ethyl]amino]carbonyl]benzoyl]-3-[(thiophene-2-carbonyl)amino]-L alanine.  
     
     
         66 . A compound of  claim 1  having the formula  
       
         
           
           
               
               
           
         
         wherein U, V, and W are independently hydrogen, halogen, or lower alkyl provided U and V are not both hydrogen;  
         X is carbonyl, phenyl-substituted loweralkylene, or sulfonyl;  
         Y is lower alkylene which may be substituted by one or more of amino, substituted amino, lower alkyl, or cyclo lower alkyl; or Y is lower alkenylene or lower alkylenethio; and k is 0 or 1; when k is 1, Z is:  
         hydrogen, lower alkylthio, —COOH, —CONH 2 , or amino, or when k is 0 or 1, Z is: 1-adamantyl, diphenylmethyl, 3-[[(5-chloropyridin-2-yl)amino]carbonyl]pyrazin-2-yl, or Z is one of the following: 
 cycloalkyl or aryl containing 0 to 3 heteroatoms which may be the same or different, or a fused ring system containing two or three rings which rings are independently cycloalkyl or aryl containing 0 to 3 heteroatoms which may be the same or different, any of which rings may be unsubstituted, or substituted with at least one of: 
 halogen, cyano, amino, substituted amino, aminosulfonyl, nitro, oxo, hydroxy, aryl, aryloxy, unsubstituted lower alkyl, halogen-substituted lower alkyl, lower alkoxy-substituted lower alkyl, lower alkanesulfonyl, lower alkylthio, acetyl, aminocarbonyl, hydrazino, carboxy, lower alkoxycarbonyl, or acetoxy.  
 
 
       
     
     
         67 . A compound of  claim 1  having the formula  
       
         
           
           
               
               
           
         
         wherein U is fluorine or chlorine; Y is methylene or k is 0; Z is one of the following:  
         cycloalkyl or aryl containing 0 to 3 heteroatoms which may be the same or different, or a fused ring system containing two or three rings which rings are independently cycloalkyl or aryl containing 0 to 3 heteroatoms which may be the same or different, any of which rings may be unsubstituted, or substituted with at least one of: 
 halogen, cyano, amino, substituted amino, aminosulfonyl, nitro, oxo, hydroxy, aryl, aryloxy, unsubstituted lower alkyl, halogen-substituted lower alkyl, lower alkoxy-substituted lower alkyl, lower alkoxy, lower alkanesulfonyl, lower alkylthio, acetyl, aminocarbonyl, hydrazino, carboxy, lower alkoxycarbonyl, or acetoxy.  
 
       
     
     
         68 . A compound of formula  
       
         
           
           
               
               
           
         
         wherein A 3  is hydrogen, hydroxy, amino, or halogen and B 3  is amino, carboxy, hydrogen, hydroxy, cyano, trifluoromethyl, halogen, lower alkyl, or lower alkoxy;  
         R 23  is a group of the formula  
         
           
             
             
                 
                 
             
           
         
         where R 33  is hydrogen, carboxy, or lower alkyl; U 3 , V 3 , and W 3  are independently hydrogen, halogen, or lower alkyl provided U 3  and V 3  are not both hydrogen; R 4  is hydrogen, lower alkyl, or aryl-lower-alkyl which can be unsubstituted or substituted with at least one of halogen, cyano, amino, substituted amino, aminosulfonyl, nitro, hydroxy, aryl, aryloxy, unsubstituted lower alkyl, halogen-substituted lower alkyl, lower alkoxy-substituted lower alkyl, lower alkoxy, carboxy, lower alkoxycarbonyl, or acetoxy  
         and pharmaceutically acceptable salts and esters thereof.  
       
     
     
         69 . A compound of  claim 68  which is N-[2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]carbonyl]benzoyl]-3-(aminoiminomethyl) amino-L-alanine.  
     
     
         70 . A compound of formula:  
       
         
           
           
               
               
           
         
       
       wherein R 1  is a group of the formula  
       
         
           
           
               
               
           
         
         where A is hydrogen, hydroxy, amino, or halogen and B is amino, carboxy, hydrogen, hydroxy, cyano, trifluoromethyl, halogen, lower alkyl, or lower alkoxy; R 2  is a group of the formula  
         
           
             
             
                 
                 
             
           
         
         where R 3  is hydrogen, carboxy, or lower alkyl;  
         n is 0or 1;  
         U, V, and W are independently hydrogen, halogen, or lower alkyl provided U and  
         V are not both hydrogen;  
         X is carbonyl, phenyl-substituted loweralkylene, or sulfonyl;  
         Y is lower alkylene which may be substituted by one or more of amino, substituted amino, loweralkyl, or cyclo lower alkyl, or Y is lower alkenylene or lower alkylenethio; k is 0 or 1; when k is 1, Z is:  
         hydrogen, lower alkylthio, —COOH, —CONH 2 , or amino, or when k is 0 or 1,Z is: 1-adamantyl, diphenylmethyl, 3-[[(5-chloropyridin-2-yl)amino]carbonyl]pyrazin 2-yl, hydroxy, phenylmethoxy, 2-chloro-4-[[[(3-hydroxyphenyl)methyl]amino]-carbonyl]phenyl, [(2,6-dichlorophenyl)methoxy]phenyl, or Z is one of the following: 
 cycloalkyl or aryl containing 0 to 3 heteroatoms which may be the same or different, or a fused ring system containing two or three rings which rings are independently cycloalkyl or aryl containing 0 to 3 heteroatoms which may be the same or different, any of which rings may be unsubstituted, or substituted with at least one of: 
 halogen, cyano, amino, substituted amino, aminosulfonyl, nitro, oxo, hydroxy, aryl, aryloxy, unsubstituted lower alkyl, halogen-substituted lower alkyl, lower alkoxy-substituted lower alkyl lower alkoxy, lower alkanesulfonyl, lower alkylthio, acetyl, aminocarbonyl, hydrazino, carboxy, lower alkoxycarbonyl, acetoxy, or amino loweralkyl;  
 
 
         R 6  is lower alkyl or —CH 2 CH  2 —R 7  where R 7  is —N(CH 3 ) 2 ,  
         
           
             
             
                 
                 
             
           
         
         where R 8  is hydrogen or methyl and R 9  is lower alkyl or lower cycloalkyl; and pharmaceutically acceptable salts and esters thereof.  
       
     
     
         71 . A compound of  claim 70  wherein R 6  is ethyl.  
     
     
         72 . A compound of  claim 70  wherein R 6  is CH 2 CH  2 —R 7.    
     
     
         73 . A compound of  claim 72  wherein R 7  is —N(CH 3 ) 2 ,  
       
         
           
           
               
               
           
         
       
     
     
         74 . A compound of  claim 70  wherein R 6  is  
       
         
           
           
               
               
           
         
       
     
     
         75 . A compound of  claim 74  wherein R 8  is hydrogen or methyl.  
     
     
         76 . A compound of  claim 74  wherein R 9  is ethyl or cyclohexyl.  
     
     
         77 . A pharmaceutical composition which comprises a compound of  claim 1  and a pharmaceutically acceptable carrier.  
     
     
         78 . A pharmaceutical composition of  claim 77  which comprises a compound of  claim 30  and a pharmaceutically acceptable carrier.  
     
     
         79 . A method of attenuating tissue damage resulting from reperfusion injury following acute myocardial infarction which comprises administering an amount of a compound of  claim 1  effective to reduce inflammation in tissue affected by acute myocardial infarction.  
     
     
         80 . A method of  claim 79  wherein the amount of compound is from about 1.0 to about 100 mg/kg/day.  
     
     
         81 . A method of  claim 79  wherein the amount of compound administered provides a plasma level of 5 mg/ml of plasma in a patient to whom the compound is administered.