Morpholinyl and pyrrolidinyl analogs

Abstract

The present invention relates to morpholinyl, and pyrrolidinyl analogs, pharmaceutical compositions containing them, and their use as antagonists of urotensin II.

1 . A compound of Formula (I): 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is: 
       
       
         
           
           
               
               
           
         
         A is (CH 2 ) n ; 
         n is 1 or 2; 
         the group (a) may be unsubstituted or substituted by one, two, or three substituents chosen from: halo, OC 1-3  alkyl, OH, CN, C(O)OH, NR 7 R 8 , OCF 3 , C(O)NR 9 R 10 , SO 2 C 1-3  alkyl, SO 2 C 3-6  cycloalkyl, SO 2 -phenyl, SO 2 NR 9 R 10 , CF 3 , and NO 2 ; 
         R 2  is hydrogen, halo, OC 1-3  alkyl, NHC(O)C 1-3  alkyl, NHSO 2 C 1-3 alkyl, NHSO 2 -phenyl, NHC(O)C 3-6  cycloalkyl, or NHC(O)-phenyl; 
         R 3  is C 1-3  alkyl or C 3-6  cycloalkyl; 
         R 4 , R 5 , and R 6  are independently hydrogen or CH 3 ; 
         R 7  and R 8  are independently hydrogen, C(O)C 1-3  alkyl, C(O)C 3-6  cycloalkyl, C(O)-phenyl, C 1-6  alkyl, phenyl, SO 2 C 1-3  alkyl, SO 2 C 3-6  cycloalkyl, SO 2 -phenyl, or C(O)NHC 1-3  alkyl; 
         R 9  and R 10  are independently hydrogen, C 1-3  alkyl, C 3-6  cycloalkyl, phenyl; 
         or taken together R 9  and R 10  may form a 5 to 7 member ring optionally containing one or two heteroatoms chosen from O, N, and S; 
         X is O or a bond; 
         B is: 
       
       
         
           
           
               
               
           
         
         R 12  is hydrogen, C 1-3  alkyl, CH 2 CN, (CH 2 ) m (O)CH 3 , CH 2 C(O)NH 2 , or (CH 2 ) m OH; 
         R 13  is hydrogen, halo, C 1-3  alkyl, CF 3 , or OC 1-3  alkyl; 
         m is 2 or 3; 
         R 14  is hydrogen, halo, C 1-3  alkyl, OC 1-3  alkyl, OCF 3 , CF 3 , C(O)NR 15 R 16 , or C(O)OC 1-3  alkyl; and 
         R 15  and R 16  are independently hydrogen, C 1-3  alkyl, C 3-6  cycloalkyl, or phenyl; 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         2 . A compound of  claim 1  wherein:
 R 1  is phenyl substituted by one or two halo, OC 1-3 alkyl, CN, C(O)OH, NR 7 R 8 , C(O)NR 9 R 10 , SO 2 C 1-3  alkyl, or SO 2 NR 11 R 12 ;   R 2  is hydrogen or halo;   R 3  is methyl;   R 4  is hydrogen or CH 3 ;   R 5  and R 6  are hydrogen;   R 7  and R 8  are independently hydrogen, C(O)C 1-3 alkyl, C 1-6 alkyl, SO 2 C 1-3  alkyl, or C(O)NHC 1-3 alkyl;   R 9  and R 10  are independently H, C 1-3 alkyl;   or taken together R 9  and R 10  form a pyrrolidine, morpholine, or piperidine group;   X is O or a bond;   B is:   
       
         
           
           
               
               
           
         
         R 12  is methyl, CH 2 CN, (CH 2 ) m (O)CH 3 , or CH 2 C(O)NH 2 ; 
         R 13  is hydrogen or halo; 
         m is 2; and 
         R 14  is hydrogen or halo; 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         3 . A compound of  claims 1  and  2  wherein:
 R 1  is phenyl substituted by one or two OC 1-3 alkyl, C(O)OH, or C(O)NR 9 R 10 ;   R 2  is hydrogen or halo;   R 3  is methyl;   R 4  is hydrogen or CH 3 ;   R 5  and R 6  are hydrogen;   R 9  and R 10  are independently hydrogen, C 1-3 alkyl;   or taken together R 9  and R 10  form a pyrrolidine, morpholine, or piperidine group;   X is O or a bond;   B is:   
       
         
           
           
               
               
           
         
       
       or
 R 12  is methyl, CH 2 CN, (CH 2 ) m (O)CH 3 , or CH 2 C(O)NH 2 ; 
 R 13  is hydrogen or halo; 
 m is 2; and 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         4 . A compound of  claim 1  selected from:
 N-[1-(4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N-methyl-2-(2-oxo-1,3-benzoxazol-3-(2H)-yl)acetamide;   N-[1-(4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-2-(5-chloro-2-oxo-1,3-benzoxazol-3(2H)-yl-N-methylacetamide ;   N 1 -[1-(4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N 2 -(cyanomethyl)-N 2 -(3,4-dichlorophenyl)-N 1 -methylglycinamide;   N-[1-(4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-2-(6,7-dichloro-2-oxo-1(2H)-quinoxalinyl)-N-methylacetamide;   N-[1-(4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-2-(5-chloro-2-oxo-1,3-benzothiazol-3(2H)-yl)-N-methylacetamide;   N-[(1R)-1-(4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-2-(5-chloro-2-oxo-1,3-benzoxazol-3(2H)-yl-N-methylacetamide;   N-[1-(4-biphenylyl)-2-(4-morpholinyl)ethyl]-2-(5-chloro-2-oxo-1,3-benzothiazol-3(2H)-yl)-N-methylacetamide;   N-[1-(4-biphenylyl)-2-(4-morpholinyl)ethyl]-2-(6,7-dichloro-2-oxo-1(2H)-quinoxalinyl)-N-methylacetamide;   N-[1-(4-biphenylyl)-2-(4-morpholinyl)ethyl]-2-(6,7-dichloro-2-oxo-1(2H)-quinolinyl)-N-methylacetamide;   N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethyl-N 1 -[1-[2′-(methyloxy)-4-biphenylyl]-2-(1-pyrrolidinyl)ethyl]glycinamide;   N 2 -(3,4-dichlorophenyl)-N 1 -[1-(3′-hydroxy-4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N 1 ,N 2 -dimethylglycinamide;   N 1 -[1-(3′-cyano-4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethylglycinamide;   N 1 -[1-(4′-cyano-4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethylglycinamide;   N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethyl-N 1 -[1-{4′-[(methylsulfonyl)amino]-4-biphenylyl}-2-(1-pyrrolidinyl)ethyl]glycinamide;   N1-[1-[2′,3′-bis(methyloxy)-4-biphenylyl]-2-(1-pyrrolidinyl)ethyl]-N2-(3,4-dichloropheynyl)-N1,N2-dimethylglycinamide;   N 1 -[1-[3′-(acetylamino)-4-biphenylyl]-2-(1-pyrrolidinyl)ethyl]-N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethylglycinamide;   N 1 -[1-[4′-(acetylamino)-4-biphenylyl]-2-(1-pyrrolidinyl)ethyl]-N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethylglycinamide;   N 2 -(3,4-dichlorophenyl)-N 1 -[1-(2′-hydroxy-4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N 1 ,N 2 -dimethylglycinamide;   N 2 -(3,4-dichlorophenyl)-N 1 -[1-[3′-(dimethylamino)-4-biphenylyl]-2-(1-pyrrolidinyl)ethyl]-N 1 ,N 2 -dimethylglycinamide;   N 1 -[1-[2′-(acetylamino)-4-biphenylyl]-2-(1-pyrrolidinyl)ethyl]-N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethylglycinamide;   N 2 -(3,4-dichlorophenyl)-N 1 -[1-[4′-(dimethylamino)-4-biphenylyl]-2-(1-pyrrolidinyl)ethyl]-N 1 ,N 2 -dimethylglycinamide;   N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethyl-N 1 -[1-{3′-[(methylsulfonyl)amino]-4-biphenylyl}-2-(1-pyrrolidinyl)ethyl]glycinamide;   N 1 -[1-[3′,4′-bis(methyloxy)-4-biphenylyl]-2-(1-pyrrolidinyl)ethyl]-N 2 -(3,4-dichloropheynyl)-N 1 ,N 2 -dimethylglycinamide;   N 1 -[1-(3′-amino-4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethylglycinamide;   N-cyclopropyl-4′-[1-[[N-(3,4-dichlorophenyl)-N-methylglycyl](methyl)amino]-2-(1-pyrrolidinyl)ethyl]-3-biphenylcarboxamide;   4′-[1-[[N-(3,4-dichlorophenyl)-N-methylglycyl](methyl)amino]-2-(1-pyrrolidinyl)ethyl]-N-(1-methylethyl)-3-biphenylcarboxamide;   4′-[1-[[N-(3,4-dichlorophenyl)-N-methylglycyl](methyl)amino]-2-(1-pyrrolidinyl)ethyl]-5-fluoro-N-methyl-3-biphenylcarboxamide;   N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethyl-N 1 -{2-(1-pyrrolidinyl)-1-[4′-(1-pyrrolidinylcarbonyl)-4-biphenylyl]ethyl} glycinamide;   N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethyl-N 1 -[1-[3′-(4-morpholinylcarbonyl)-4-biphenylyl]-2-(1-pyrrolidinyl)ethyl]glycinamide;   N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethyl-N 1 -[1-{2′-[(methylsulfonyl)amino]-4-biphenylyl}-2-(1-pyrrolidinyl)ethyl]glycinamide;   N 2 -(3,4-dichlorophenyl)-N 1 -[1-{2′-[(dimethylamino)sulfonyl]-4-biphenylyl}-2-(1-pyrrolidinyl)ethyl]-N 1 ,N 2 -dimethylglycinamide;   N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethyl-N 1 -[1-[4′-(methylsulfonyl)-4-biphenylyl]-2-(1-pyrrolidinyl)ethyl]glycinamide;   4′-[1-[[N-(cyanomethyl)-N-(3,4-dichlorophenyl)glycyl](methyl)amino]-2-(1-pyrrolidinyl)ethyl]-4-biphenylcarboxylic acid;   N 2 -(cyanomethyl)-N 2 -(3,4-dichlorophenyl)-N 1 -methyl-N 1 -[1-{3′-[(1-methylethyl)oxy]-4-biphenylyl}-2-(1-pyrrolidinyl)ethyl]glycinamide;   N 2 -(cyanomethyl)-N 2 -(3,4-dichlorophenyl)-N 1 -methyl-N 1 -[1-{3′-[(methylsulfonyl)amino]-4-biphenylyl}-2-(1-pyrrolidinyl)ethyl]glycinamide;   N 2 -(cyanomethyl)-N 2 -(3,4-dichlorophenyl)-N 1 -[1-[4′-(dimethylamino)-4-biphenylyl]-2-(1-pyrrolidinyl)ethyl]-N 1 -methylglycinamide;   N 1 -[1-[4′-(acetylamino)-4-biphenylyl]-2-(1-pyrrolidinyl)ethyl]-N 2 -(cyanomethyl)-N 2 -(3,4-dichlorophenyl)-N 1 -methylglycinamide;   N 2 -(cyanomethyl)-N 2 -(3,4-dichlorophenyl)-N 1 -methyl-N 1 -[1-[3′-(methyloxy)-4-biphenylyl]-2-(1-pyrrolidinyl)ethyl]glycinamide;   N 1 -[1-[3′,4′-bis(methyloxy)-4-biphenylyl]-2-(1-pyrrolidinyl)ethyl]-N 2 -(cyanomethyl)-N 2 -(3,4-dichlorophenyl)-N 1 -methylglycinamide;   4′-[1-[[N-(3,4-dichlorophenyl)-N-methylglycyl](methyl)amino]-2-(1-pyrrolidinyl)ethyl]-2-biphenylcarboxamide;   4′-[1-[[N-(3,4-dichlorophenyl)-N-methylglycyl](methyl)amino]-2-(1-pyrrolidinyl)ethyl]-3-biphenylcarboxamide;   4′-[1-[[N-(3,4-dichlorophenyl)-N-methylglycyl](methyl)amino]-2-(1-pyrrolidinyl)ethyl]-4-biphenylcarboxamideTrifluoroacetate;   4′-[1-[[N-(3,4-dichlorophenyl)-N-methylglycyl](methyl)amino]-2-(1-pyrrolidinyl)ethyl]-N-methyl-3-biphenylcarboxamide;   4′-[1-[[N-(3,4-dichlorophenyl)-N-methylglycyl](methyl)amino]-2-(1-pyrrolidinyl)ethyl]-N-methyl-4-biphenylcarboxamide;   4′-[1-[[N-(3,4-dichlorophenyl)-N-methylglycyl](methyl)amino]-2-(1-pyrrolidinyl)ethyl]-N,N-dimethyl-3-biphenylcarboxamide;   4′-[1-[[N-(3,4-dichlorophenyl)-N-methylglycyl](methyl)amino]-2-(1-pyrrolidinyl)ethyl]-N,N-dimethyl-4-biphenylcarboxamide;   N-[1-(4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N-methyl-2-[7-(methyloxy)-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl]acetamide;   (R) N-[1-(4-biphenylyl)-2-(4-morpholinyl)ethyl]-2-(6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)-N-methylacetamide;   N-[1-(4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N-methyl-2-[6-(methyloxy)-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl]acetamide;   N-[1-(4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N-methyl-2-{3-oxo-6-[(trifluoromethyl)oxy]-2,3-dihydro-4H-1,4-benzoxazin-4-yl}acetamide;   N-[1-(4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N-methyl-2-[5 -(methyloxy)-2-oxo-1,3-benzoxazol-3(2H)-yl]acetamide;   N-[1-(4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N-methyl-2-[2-oxo-5-[(trifluoromethyl)oxy[-1,3-benzoxazol-3(2H)-yl]acetamide;   N-[1-(4-biphenylyl)-2-(4-morpholinyl)ethyl]-2-(5,6-dichloro-2-oxo-1(2H)-quinolinyl)-N-methylacetamide;   N-[1-(4-biphenylyl)-2-(4-morpholinyl)ethyl]-2-(6,7-dimethyl-2-oxo-1(2H)-quinolinyl)-N-methylacetamide; and   N-[1-(4-biphenylyl)-2-(4-morpholinyl)ethyl]-2-(6,7-dimethyl-2-oxo-1(2H)-quinoxalinyl)-N-methylacetamide;   or a pharmaceutically acceptable salt thereof.   
     
     
         5 . A compound of  claim 1  selected from:
 N 1 -[1-(4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N 2 -(3,4-dichlorophenyl)-N 1 -,N 2 -dimethylglycinamide;   N-[(1S)-1-(4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-2-(5-chloro-2-oxo-1,3-benzoxazol-3(2H)-yl-N-methylacetamide;   N-[1-(4-biphenylyl)-2-(4-morpholinyl)ethyl]-2-(5-chloro-2-oxo-1,3-benzoxazol-3(2H)-yl)-N-methylacetamide;   N 1 -[1-(4-biphenylyl)-2-(4-morpholinyl)ethyl]-N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethylglycinamide;   N 1 -[1-(4-biphenylyl)-2-(4-morpholinyl)ethyl]-N 2 -(cyanomethyl)-N 2 -(3,4-dichlorophenyl)-N 1 -methylglycinamide;   N 1 -[1-(4′-chloro-4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethylglycinamide;   N 1 -[1-(2′-chloro-4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethylglycinamide;   N 1 -[1-(3′-chloro-4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethylglycinamide;   N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethyl-N 1 -[1-[3 ’-(methyloxy)-4-biphenylyl]-2-(1-pyrrolidinyl)ethyl]glycinamide;   N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethyl-N 1 -[1-[4′-(methyloxy)-4-biphenylyl]-2-(1-pyrrolidinyl)ethyl]glycinamide;   N 1 -[1-(3′,4′-dichloro-4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethylglycinamide;   N 1 -[1-(2′,3′-dichloro-4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethylglycinamide;   N 1 -[1-(2′,4′-dichloro-4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethylglycinamide;   N 1 -[1-(3′,5′-dichloro-4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethylglycinamide;   N 1 -[1-(3′-chloro-4′-fluoro-4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethylglycinamide;   N 1 -[1-[4-(1,3-benzodioxol-5-yl)phenyl]-2-(1-pyrrolidinyl)ethyl]-N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethylglycinamide;   4′-[1-[[N-(3,4-dichlorophenyl)-N-methylglycyl](methyl)amino]-2-(1-pyrrolidinyl)ethyl]-4-biphenylcarboxylic acid;   N 2 -(3,4-dichlorophenyl)-N 1 -[1-(4′-hydroxy-4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N 1 ,N 2 -dimethylglycinamide;   N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethyl-N 1 -[1-{2′-[(1-methylethyl)oxy]-4-biphenylyl}-2-(1-pyrrolidinyl)ethyl]glycinamide;   N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethyl-N 1 -[1-{3′-[(1-methylethyl)oxy]-4-biphenylyl}-2-(1-pyrrolidinyl)ethyl]glycinamide;   N 2 -(3,4-dichlorophenyl)-N 1 -[1-[3′-(ethyloxy)-4-biphenylyl]-2-(1-pyrrolidinyl)ethyl]-N 1 ,N 2 -dimethylglycinamide;   N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethyl-N 1 -(2-(1-pyrrolidinyl)-1-{3′-[trifluoromethyl)oxy]-4-biphenylyl}ethyl)glycinamide;   N 2 -(3,4-dichlorophenyl)-N 1 -[1-[4-(2,3-dihydro-1,4-benzodioxin-5-yl)phenyl]-2-[(1-pyrrolidinyl)ethyl]-N 1 ,N 2 -dimethylglycinamide;   N-cyclopropyl 4′-[1-[[N-(3,4-dichlorophenyl)-N-methylglycyl](methyl)amino]-2-(1-pyrrolidinyl)ethyl]-4-biphenylcarboxamide;   4′-[1-[[N-(3,4-dichlorophenyl)-N-methylglycyl](methyl)amino]-2-(1-pyrrolidinyl)ethyl]-N-(1-methylethyl)-4-biphenylcarboxamide;   3-chloro-4′-[1-[[N-(3,4-dichlorophenyl)-N-methylglycyl](methyl)amino]-2-(1-pyrrolidinyl)ethyl]-4-biphenylcarboxamide;   3-chloro-4′-[1-[[N-(3,4-dichlorophenyl)-N-methylglycyl](methyl)amino]-2-(1-pyrrolidinyl)ethyl]-N-methyl-4-biphenylcarboxamide;   3-chloro-4′-[1-[[N-(3,4-dichlorophenyl)-N-methylglycyl](methyl)amino]-2-(1-pyrrolidinyl)ethyl]-N,N-dimethyl-4-biphenylcarboxamide;   N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethyl-N 1 -[1-[4′-(4-morpholinylcarbonyl)-4-biphenylyl]-2-(1-pyrrolidinyl)ethyl]glycinamide;   N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethyl-N 1 -[1-[4′-(1-piperidinylcarbonyl)-4-biphenylyl]-2-(1-pyrrolidinyl)ethyl]glycinamide;   N 2 -(3,4-dichlorophenyl)-N 1 -[1-[4′-(ethylsulfonyl)-4-biphenylyl]-2-(1-pyrrolidinyl)ethyl]-N 1 ,N 2 -dimethylglycinamide;   N 1 -[1-[4′-(aminosulfonyl)-4-biphenylyl]-2-(1-pyrrolidinyl)ethyl]-N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethylglycinamide;   N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethyl-N 1 -[1-{4′-[(methylamino)sulfonyl]-4-biphenylyl}-2-(1-pyrrolidinyl)ethyl]glycinamide;   N 2 -(3,4-dichlorophenyl)-N 1 -[1-{4′-[(dimethylamino)sulfonyl]-4-biphenylyl}-2-(1-pyrrolidinyl)ethyl]-N 1 ,N 2 -dimethylglycinamide;   N 1 -[1-(4′-chloro-3-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethylglycinamide;   N 2 -(3,4-dichlorophenyl)-N 1 -[1-[4′-(dimethylamino)-3-biphenylyl]-2-(1-pyrrolidinyl)ethyl]-N 1 ,N 2 -dimethylglycinamide;   N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethyl-N 1 -[1-[3′-(methyloxy)-3-biphenylyl]-2-(1-pyrrolidinyl)ethyl]glycinamide;   N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethyl-N 1 -[1-[2′-(methyloxy)-3-biphenylyl]-2-(1-pyrrolidinyl)ethyl]glycinamide;   N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethyl-N 1 -[1-[4′-(methyloxy)-3-biphenylyl]-2-(1-pyrrolidinyl)ethyl]glycinamide;   N 1 -[1-(2′-chloro-3-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethylglycinamide;   N 1 -[1-(3-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N 2 -(3,4-dichlorophenyl)-N 1 ,N 2 -dimethylglycinamide;   N-[1-(3-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-2-(6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)-N-methylacetamide;   N 2 -(3,4-dichlorophenyl)-N 1 -[1-(2′-hydroxy-3-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N 1 ,N 2 -dimethylglycinamide;   N 2 -(3,4-dichlorophenyl)-N 1 -[1-(4′-hydroxy-3-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N 1 ,N 2 -dimethylglycinamide;   2-(6,7-dichloro-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)-N-methyl-N-{2-(4-morpholinyl)-1-[4′-(1-pyrrolidinylcarbonyl)-4-biphenylyl]ethyl}acetamide;   2-[(2-amino -2-oxo ethyl)(3,4-dichlorophenyl)amino]-N-methyl-N-[1-[3′-(methyloxy)-4-biphenylyl]-2-(4-morpholinyl)ethyl]acetamide;   2-[(2-amino-2-oxoethyl)(3,4-dichlorophenyl)amino]-N-[1-(3′-cyano-4-biphenylyl)-2-(4-morpholinyl)ethyl]-N-methylacetamide;   2-[(2-amino-2-oxoethyl)(3,4-dichlorophenyl)amino]-N-[1-[4′-(dimethylamino)-4-biphenylyl]-2-(4-morpholinyl)ethyl]-N-methylacetamide;   2-[2-amino-2-oxoethyl)(3,4-dichlorophenyl)amino]-N-[1-[2′,3′-bis(methyloxy)-4-biphenylyl]-2-(4-morpholinyl)ethyl]-N-methylacetamide;   N-[1-(4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N-methyl-2-[6-methyl-5-(methyloxy)-2-oxo-1,3-benzoxazol-3(2H)-yl]acetamide;   N-[1-(4-biphenylyl)-2-(4-morpholinyl)ethyl]-N-methyl-2-[6-methyl-5-(methyloxy)-2-oxo-1,3-benzoxazol-3(2H)-yl]acetamide;   N-[1-(4-biphenylyl)-1-methyl-2-(1-pyrrolidinyl)ethyl]-2-(5-chloro-2-oxo-1,3-benzoxazol-3(2H)-yl)-N-methylacetamide;   N1-[1-(4-biphenylyl)-1-methyl-2-(1-pyrrolidinyl)ethyl]-N2-(cyanomethyl)-N2-(3,4-dichlorophenyl)-N1-methylglycinamide;   N-[1-(4-biphenylyl)-1-methyl-2-(1-pyrrolidinyl)ethyl]-2-[5-chloro-2-oxo-1,3-benzothiazol-3(2H)-yl)-N-methylacetamide;   N-[1-(4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N-methyl-2-[6-(methyloxy)-2-oxo-1,3-benzoxazol-3(2H)-yl]acetamide;   N 1 -[1-(4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N 2 -(3,4-dichlorophenyl)-N 1 -methyl-N 2 -[2-(methyloxy)ethyl]glycinamide;   N 1 -[1-(4-biphenylyl)-2-(1-pyrrolidinyl)ethyl]-N 2 -(3,4-dichlorophenyl)-N 1 , 2-dimethylalaninamide;   N-[1-(4-biphenylyl)-2-(4-morpholinyl)ethyl]-2-(5,6-dimethyl-2-oxo-1(2H)-quinolinyl)-N-methylacetamide ;   or a pharmaceutically acceptable salt thereof.   
     
     
         6 .- 9 . (canceled) 
     
     
         10 . A pharmaceutical composition comprising a compound of formula (I)  claim 1  and a pharmaceutically acceptable carrier or excipient. 
     
     
         11 . A method of treating congestive heart failure, stroke, ischemic heart disease, angina, myocardial ischemia, overactive bladder, or cardiac arrhythmia which comprises administering to a patient in need thereof, a compound of Formula I of  claim 1 . 
     
     
         12 . A method of treating hypertension which comprises administering to a patient in need thereof, a compound of Formula I of  claim 1 .