Dihydropyrimidines and uses thereof

Abstract

This invention is directed to dihydropyrimidine compounds which are selective antagonists for human α 1A receptors. This invention is also related to uses of these compounds for lowering intraocular pressure, inhibiting cholesterol synthesis, relaxing lower urinary tract tissue, the treatment of benign prostatic hyperplasia, impotency, cardiac arrhythmia and for the treatment of any disease where the antagonism of the α 1A receptor may be useful. The invention further provides a pharmaceutical composition comprising a therapeutically effective amount of the above-defined compounds and a pharmaceutically acceptable carrier.

What is claimed is:  
     
         1 . A compound having the structure:  
       
         
           
           
               
               
           
         
         wherein A is  
         
           
             
             
                 
                 
             
           
         
         wherein each of Y 1 , Y 2 , Y 3 , Y 4  and Y 5  is independently —H; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 ′-C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 3 , —OCOR 3 , —COR 3 ,  13  CONHR 3 , —CON(R 3 ) 2 , or —COOR 3 ; or any two of Y 1 , Y 2 , Y 3 , Y 4  and Y 5  present on adjacent carbon atoms can constitute a methylenedioxy group;  
         wherein X is S; O; or NR 3 ;  
         wherein R 1  is —H; —NO 2 ; —CN; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; —N(R 3 ) 2 ; —OR 3 ; —(CH 2 ) p OR 3 ; —COR 3 ; —CO 2 R 3 ; or —CON(R 3 ) 2 ;  
         wherein R 2  is —H; straight chained or branched C 1 -C 7  alkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; C 3 -C 10  cycloalkyl-C 1 -C 10 -alkyl, C 3 -C 10  cycloalkyl-C 1 -C 10 -monofluoroalkyl or C 3 -C 10  cycloalkyl-C 1 -C 10 -polyfluoroalkyl; —CN; —CH 2 XR 3 , —CH 2 X(CH 2 ) p NHR 3 , —(CH 2 ) n NHR 3 , —CH 2 X(CH 2 ) p N(R 3 ) 2 , —CH 2 X(CH 2 ) p N 3 , or —CH 2 X(CH 2 ) p NHCXR 7 ; or —OR 3 ;  
         wherein each p is independently an integer from 1 to 7; wherein each n is independently an integer from 0 to 5;  
         wherein each R 3  is independently —H; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl;  
         wherein R 4  is  
         
           
             
             
                 
                 
             
           
         
         wherein Z′ is (CH 2 ) o , CO, (CH 2 ) o CO, or CO(CH 2 ) o ;  
         wherein each V is independently O; S; CH 2 ; CR 5 R 7 ; C(R 7 ) 2 ; or NR 7 ;  
         wherein each m is independently an integer from 0 to 3; wherein o is an integer from 1 to 3;  
         wherein each R is independently —H; —F; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; —N(R 3 ) 2 ; —NO 2 ; —CN; —CO 2 R 3 ; or —OR 3 ;  
         wherein R 5  and R 7  each independently may be —H; F; Cl; Br; I; —COR 3 ; —CO 2 R 3 ; —CON(R 3 ) 2 ; —CN; —NO 2 ; —N(R 3 ) 2 ; —OR 3 ; —SR 3 ; —(CH 2 ) p OR 3 ; -(CH 2 ) p SR 3 ; straight chained or branched C 1 -C 7  alkyl, aminoalkyl, carboxamidoalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl, or C 3 -C 7  cycloalkyl or cycloalkenyl; wherein the alkyl, aminoalkyl, carboxamidoalkyl, alkenyl, alkynyl, cycloalkyl or cycloalkenyl may be substituted with one or more aryl or heteroaryl, wherein the aryl or heteroaryl may be substituted with —F, —Cl, —Br, —I, —NO 2 , —CN, —OR 3 , —SR 3 , C 1 -C 3  alkyl, or carboxamido; aryl or heteroaryl, wherein the aryl or heteroaryl may be substituted with one or more —F, —Cl, —Br, —I, COR 3 , CO 2 R 3 , —CON(R 3 ) 2 , —CN, —NO 2 , —N(R 3 ) 2 , —OR 3 , —SR 3 , (CH 2 ) o OR 3 , (CH 2 ) o SR 3 ; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl, C 2 -C 7  alkynyl, C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; and  
         wherein each R 6  is independently —H; straight chained or branched C 1 -C 7  alkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; or —OR 3 ;  
         or a pharmaceutically acceptable salt thereof.  
       
     
     
         2 . The compound of  claim 1 , wherein the compound comprises the (+) enantiomer.  
     
     
         3 . The compound of  claim 1 , wherein the compound comprises the (−) enantiomer.  
     
     
         4 . The compound of  claim 1  having the structure:  
       
         
           
           
               
               
           
         
       
     
     
         5 . The compound of  claim 4 , wherein Z′ is CO and n is 0.  
     
     
         6 . The compound of  claim 5  having the structure:  
       
         
           
           
               
               
           
         
       
     
     
         7 . A compound selected from the group consisting of:  
       
         
           
           
               
               
           
         
       
     
     
         8 . A compound having the structure:  
       
         
           
           
               
               
           
         
         wherein A is  
         
           
             
             
                 
                 
             
           
         
         wherein each of Y 1 , Y 2 , Y 3 , Y 4  and Y 5  is independently —H; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; -N 3 ; —CN; —OR 3 , —OCOR 3 , —COR 3 , —CONHR 3 , —CON(R 3 ) 2 , or —COOR 3 ; or any two of Y 1 , Y 2 , Y 3 , Y 4  and Y 5  present on adjacent carbon atoms can constitute a methylenedioxy group;  
         wherein X is S; O; or NR 3 ;  
         wherein R 1  is —H; —NO 2 ; —CN; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; —N(R 3 ) 2 ; —OR 3 ; —(CH 2 ) p OR 3 ; —COR 3 ; —CO 2 R 3 ; or —CON(R 3 ) 2 ;  
         wherein R 2  is —H; straight chained or branched C 1 -C 7  alkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; C 3 -C 10  cycloalkyl-C 1 -C 10 -alkyl, C 3 -C 10  cycloalkyl-C 1 -C 10 -monofluoroalkyl or C 3 -C 10  cycloalkyl-C 1 -C 10 -polyfluoroalkyl; —CN; —CH 2 XR 3 , —CH 2 X(CH 2 ) p NHR 3 , —(CH 2 ) n NHR 3 , —CH 2 X(CH 2 ) p N(R 3 ) 2 , —CH 2 X(CH 2 ) p N 3 , or —CH 2 X(CH 2 ) p NHCXR 7 ; or —OR 3 ;  
         wherein each p is independently an integer from 1 to 7; wherein each n is independently an integer from 0 to 5;  
         wherein each R 3  is independently —H; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl;  
         wherein R 4  is  
         
           
             
             
                 
                 
             
           
         
         wherein Z is C 2 -C 7  alkenyl or alkynyl; CH 2 ; O; CO; CO 2 ; CONR 3 ; S; SO; SO 2 ; or NR 3 ;  
         wherein Z′ is (CH 2 ) o , CO, (CH 2 ) o CO, or CO(CH 2 ) o ;  
         wherein each D is independently CH 2 ; O; S; NR 3 ; CO; or CS;  
         wherein W is C═O; C═NOR 3 ; substituted or unsubstituted phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrryl, naphthyl, indolyl, imidazolyl, benzfurazanyl, benzfuranyl or benzyimidazolyl, wherein the phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrryl, naphthyl, indolyl, imidazolyl, benzfurazanyl, benzfuranyl or benzyimidazolyl is substituted with —H, —F, —Cl, —Br, —I, —NO 2 , —CN, straight chained or branched C 1 -C 7  alkyl, straight chained or branched C 1 -C 7  monofluoroalkyl, straight chained or branched C 2 -C 7  polyfluoroalkyl, straight chained or branched C 2 -C 7  alkenyl, straight chained or branched C 2 -C 7  alkynyl, C 3 -C 7  cycloalkyl, C 3 -C 7  monofluorocycloalkyl, C 3 -C 7  polyfluorocycloalkyl, C 3 -C 7  cycloalkenyl, —N(R 3 ) 2 , —OR 3 , —COR 3 , —CO 2 R 3 , or —CON(R 3 ) 2 ;  
         wherein each V is independently O; S; CH 2 ; CR 5 R 7 ; C(R 7 ) 2 ; or NR 7 ;  
         wherein each m is independently an integer from 0 to 3; wherein o is an integer from 1 to 3;  
         wherein each R is independently —H; —F; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; —N(R 3 ) 2 ; —NO 2 ; —CN; —CO 2 R 3 ; or —OR 3 ;  
         wherein R 5  is aryl or heteroaryl substituted with one or more of F; Cl; Br; I; COR 3 ; CO 2 R 3 ; —CON(R 3 ) 2 ; CN; —NO 2 ; —N(R 3 ) 2 ; —OR 3 , —SR 3 ; (CH 2 ) o OR 3 ; (CH 2 ) o SR 3 ; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl, polyfluoroalkyl, aminoalkyl, or carboxamidoalkyl; straight chained or branched C 2 -C 7  alkenyl, C 2 -C 7  alkynyl, C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl;  
         wherein each R 6  is independently —H; straight chained or branched C 1 -C 7  alkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; or —OR 3 ;  
         wherein R 7  is aryl or heteroaryl substituted with one or more of F; Cl; Br; I; COR 3 ; CO 2 R 3 ; —CON(R 3 ) 2 ; CN; —NO 2 ; —N(R 3 ) 2 ; —OR 3 , —SR 3 ; (CH 2 ) o OR 3 ; (CH 2 ) o SR 3 ; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl, polyfluoroalkyl, aminoalkyl, or carboxamidoalkyl; straight chained or branched C 2 -C 7  alkenyl, C 2 -C 7  alkynyl, C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; and  
         wherein R 8  is —H; substituted or unsubstituted benzyl, benzoyl, phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrryl, naphthyl, indolyl, imidazolyl, benzfurazanyl, benzfuranyl, benzimidazolyl or 2-keto-1-benzimidazolinyl, wherein the benzyl, benzoyl, phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrryl, naphthyl, indolyl, imidazolyl, benzfurazanyl, benzfuranyl, benzimidazolyl or 2-keto-1-benzimidazolinyl is substituted with —H, —F, —Cl, —Br, —I, —NO 2 , —CN, straight chained or branched C 1 -C 7  alkyl, straight chained or branched C 1 -C 7  monofluoroalkyl, straight chained or branched C 1 -C 7  polyfluoroalkyl, straight chained or branched C 2 -C 7  alkenyl, straight chained or branched C 2 -C 7  alkynyl, C 3 -C 7  cycloalkyl, C 3 -C 7  monofluorocycloalkyl, C 3 -C 7  polyfluorocycloalkyl, C 3 -C 7  cycloalkenyl, —N(R 3 ) 2 , —OR 3 , —COR 3 , —CO 2 R 3 , or —CON(R 3 ) 2 ; substituted or unsubstituted straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; substituted or unsubstituted straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl or cycloalkenyl, wherein the alkyl, monofluoroalkyl, polyfluoroalkyl, alkenyl, alkynyl, cycloalkyl or cycloalkenyl is substituted with —H, phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrryl, naphthyl, indolyl, imidazolyl, benzfurazanyl, benzfuranyl, benzimidazolyl, —N(R 3 ) 2 , —NO 2 , —CN, —CO 2 R 3 , —OR 3 ;  
         
           
             
             
                 
                 
             
           
         
         or a pharmaceutically acceptable salt thereof.  
       
     
     
         9 . The compound of  claim 8  having the structure:  
       
         
           
           
               
               
           
         
       
     
     
         10 . The compound of  claim 9  having the structure:  
       
         
           
           
               
               
           
         
       
     
     
         11 . The compound of  claim 10  having the structure:  
       
         
           
           
               
               
           
         
         wherein V is selected from CR 5 R 7  or NR 7  and p is selected from 1-3.  
       
     
     
         12 . The compound of  claim 11 , wherein the compound is selected from the group consisting of:  
       
         
           
           
               
               
           
         
       
     
     
         13 . A compound having the structure:  
       
         
           
           
               
               
           
         
         wherein A is  
         
           
             
             
                 
                 
             
           
         
         wherein each of Y 1 , Y 2 , Y 3 , Y 4  and Y 5  is independently —H; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 C alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; -N 3 ; —CN; —OR 4 , —OCOR 4 , —COR 4  —CONHR 4 , —CON(R 4 ) 2 , or —COOR 4 ; or any two of Y 1 , Y 2 , Y 3 , Y 4  and Y 5  present on adjacent carbon atoms can constitute a methylenedioxy group;  
         wherein X is S; O; or NR 4 ;  
         wherein B is —H; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl, polyfluoroalkyl, alkoxy or thioalkyl; straight chained or branched C 2 -C 7  alkenyl; —SCH 2 C 6 H 4 OR 4 ; —(CH 2 ) n C 6 H 5 ; —CH 2 X(CH 2 ) n NHR 4 ; —(CH 2 ) n NHR 4 ; or —OR 4 ;  
         wherein R 1  is —H; —NO 2 ; —CN; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; —N(R 4 ) 2 ; —OR 4 ; —(CH 2 ) p OR 4 ; —COR 4 ; CO 2 R 4 ; or —CON(R 4 ) 2 ;  
         wherein R 2  is —H; straight chained or branched C 1 -C 7  alkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; C 3 -C 10  cycloalkyl-C 1 -C 10 -alkyl, C 3 -C 10  cycloalkyl-C 1 -C 10 -monofluoroalkyl or C 3 -C 10  cycloalkyl-C 1 -C 10 -polyfluoroalkyl; —CN; —CH 2 XR 4 , —CH 2 X(CH 2 ) p NHR 4  —(CH 2 ) n NHR 4 , —CH 2 X(CH 2 ) p N(R 4 ) 2 , —CH 2 X(CH 2 ) p N 3  or —CH 2 X(CH 2 ) p NHCXR 7 ; or —OR 4 ;  
         wherein each p is independently an integer from 1 to 7; wherein each n is independently an integer from 0 to 5;  
         wherein R 3  is  
         
           
             
             
                 
                 
             
           
         
         wherein Z is C 2 -C 7  alkenyl or alkynyl; CH 2 ; O; CO; CO 2 ; CONR 4 ; S; SO; SO 2 ; or NR 4 ;  
         wherein Z′ is (CH 2 ) o , CO, (CH 2 ) o CO, or CO(CH 2 ) o ;  
         wherein each D is independently CH 2 ; O; S; NR; CO; or CS;  
         wherein W is C═O; C═NOR 4 ; substituted or unsubstituted phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrryl, naphthyl, indolyl, imidazolyl, benzfurazanyl, benzfuranyl or benzyimidazolyl, wherein the phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrryl, naphthyl, indolyl, imidazolyl, benzfurazanyl, benzfuranyl or benzyimidazolyl is substituted with —H, —F, —Cl, —Br, —I, —NO 2 , —CN, straight chained or branched C 1 -C 7  alkyl, straight chained or branched C 1 -C 7  monofluoroalkyl, straight chained or branched C 1 -C 7  polyfluoroalkyl, straight chained or branched C 2 -C 7  alkenyl, straight chained or branched C 2 -C 7  alkynyl, C 3 -C 7  cycloalkyl, C 3 -C 7  monofluorocycloalkyl, C 3 -C 7  polyfluorocycloalkyl, C 3 -C 7  cycloalkenyl, —N(R 4 ) 2 , —OR 4 , —COR 4 , —CO 2 R 4 , or —CON(R 4 ) 2 ;  
         wherein each V is independently O; S; CH 2 ; CR 5 R 7 ; C(R 7 ) 2 ; or NR 7 ;  
         wherein each m is independently an integer from 0 to 3; wherein o is an integer from 1 to 3;  
         wherein each R is independently —H; —F; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; —N(R 4 ) 2 ; —NO 2 ; —CN; —CO 2 R 4 ; or —OR 4 ;  
         wherein each R 4  is independently —H; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl;  
         wherein R 5  is aryl or heteroaryl substituted with one or more of F; Cl; Br; I; COR 3 ; CO 2 R 3 ; —CON(R 3 ) 2 ; CN; —NO 2 ; —N(R 3 ) 2 ; —OR 3 , —SR 3 ; (CH 2 ) o OR 3 ; (CH 2 ) o SR 3 ; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl, polyfluoroalkyl, aminoalkyl, or carboxamidoalkyl; straight chained or branched C 2 -C 7  alkenyl, C 2 -C 7  alkynyl, C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl;  
         wherein each R 6  is independently —H; straight chained or branched C 1 -C 7  alkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; or —OR 4 ;  
         wherein R 7  is aryl or heteroaryl substituted with one or more of F; Cl; Br; I; COR 3 ; CO 2 R 3 ; —CON(R 3 ) 2 ; CN; —NO 2 ; —N(R 3 ) 2 ; —OR 3 , —SR 3 ; (CH 2 ) o OR 3 ; (CH 2 ) o SR 3 ; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl, polyfluoroalkyl, aminoalkyl, or carboxamidoalkyl; straight chained or branched C 2 -C 7  alkenyl, C 2 -C 7  alkynyl, C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; and  
         wherein R 8  is —H; substituted or unsubstituted benzyl, benzoyl, phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrryl, naphthyl, indolyl, imidazolyl, benzfurazanyl, benzfuranyl, benzimidazolyl or 2-keto-1-benzimidazolinyl, wherein the benzyl, benzoyl, phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrryl, naphthyl, indolyl, imidazolyl, benzfurazanyl, benzfuranyl, benzimidazolyl or 2-keto-1-benzimidazolinyl is substituted with —H, —F, —Cl, —Br, —I, —NO 2 , —CN, straight chained or branched C 1 -C 7  alkyl, straight chained or branched C 1 -C 7  monofluoroalkyl, straight chained or branched C 1 -C 7  polyfluoroalkyl, straight chained or branched C 2 -C 7  alkenyl, straight chained or branched C 2 -C 7  alkynyl, C 3 -C 7  cycloalkyl, C 3 -C 7  monofluorocycloalkyl, C 3 -C 7  polyfluorocycloalkyl, C 3 -C 7  cycloalkenyl, —N(R) 2 , —OR, —COR 4 , —CO 2 R 4 , or —CON(R) 2 ; substituted or unsubstituted straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; substituted or unsubstituted straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl or cycloalkenyl, wherein the alkyl, monofluoroalkyl, polyfluoroalkyl, alkenyl, alkynyl, cycloalkyl or cycloalkenyl is substituted with —H, phenyl, pyridyl, thiophenyl, furanyl, pyrazinyl, pyrryl, naphthyl, indolyl, imidazolyl, benzfurazanyl, benzfuranyl, benzimidazolyl, —N(R) 2 , —NO 2 , —CN, —CO 2 R 4 , —OR 4 ;  
         
           
             
             
                 
                 
             
           
         
         or a pharmaceutically acceptable salt thereof.  
       
     
     
         14 . The compound of  claim 13 , wherein the compound comprises the (−) enantiomer.  
     
     
         15 . The compound of  claim 13 , wherein the compound comprises the (+) enantiomer.  
     
     
         16 . The compound of  claim 13  having the structure:  
       
         
           
           
               
               
           
         
       
     
     
         17 . The compound of  claim 16  having the structure:  
       
         
           
           
               
               
           
         
       
     
     
         18 . The compound of  claim 17 , wherein the compound is selected from the group consisting of:  
       
         
           
           
               
               
           
         
       
     
     
         19 . A compound having the structure:  
       
         
           
           
               
               
           
         
         wherein A is  
         
           
             
             
                 
                 
             
           
         
         wherein each of Y 1 , Y 2 , Y 3 , Y 4  and Y 5  is independently —H; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; —F, —Cl, —Br, or —I; —NO 2 ; —N 3 ; —CN; —OR 4 , —OCOR 4 , —COR 4 , —CONHR 4 , —CON(R 4 ) 2 , or —COOR 4 ; or any two of Y 1 , Y 2 , Y 3 , Y 4  and Y 5  present on adjacent carbon atoms can constitute a methylenedioxy group;  
         wherein X is S; O; or NR 4 ;  
         wherein B is —H; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl, polyfluoroalkyl, alkoxy or thioalkyl; straight chained or branched C 2 -C 7  alkenyl; —SCH 2 C 6 H 4 OR 4 ; —(CH 2 ) n C 6 H 5 ; —CH 2 X(CH 2 ) n NHR 4 ; —(CH 2 ) n NHR 4 ; or —OR 4 ;  
         wherein R 1  is —H; —NO 2 ; —CN; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; —N(R 4 ) 2 ; —OR 4 ; —(CH 2 ) p OR 4 ; —COR 4 ; CO 2 R 4 ; or —CON(R 4 ) 2 ;  
         wherein R 2  is —H; straight chained or branched C 1 -C 7  alkyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; C 3 -C 10  cycloalkyl-C 1 -C 10 -alkyl, C 3 -C 10  cycloalkyl-C 1 -C 10 -monofluoroalkyl or C 3 -C 10  cycloalkyl-C 1 -C 10 -polyfluoroalkyl; —CN; —CH 2 XR 4 , —CH 2 X(CH 2 ) p NHR 4 , —(CH 2 ) n NHR 4 , —CH 2 X(CH 2 ) p N(R 4 ) 2 , —CH 2 X(CH 2 ) p N 3 , or —CH 2 X(CH 2 ) p NHCXR 7 ; or —OR 4 ;  
         wherein each p is independently an integer from 1 to 7; wherein each n is independently an integer from 0 to 5;  
         wherein R 3  is  
         
           
             
             
                 
                 
             
           
         
         wherein Z′ is (CH 2 ) o , CO, (CH 2 ) o CO, or CO(CH 2 ) o ;  
         wherein each V is independently O; S; CH 2 ; CR 5 R 7 ; C(R 7 ) 2 ; or NR 7 ;  
         wherein each m is independently an integer from 0 to 3; wherein 0 is an integer from 1 to 3;  
         wherein each R is independently —H; —F; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; —N(R 4 ) 2 ; —NO 2 ; —CN; —CO 2 R 4 ; or —OR 4 ;  
         wherein each R 4  is independently —H; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl;  
         wherein R 5  and R 7  each independently may be —H; F; Cl; Br; I; —COR 3 ; —CO 2 R 3 ; —CON(R 3 ) 2 , —CN; —NO 2 ; —N(R 3 ) 2 , —OR 3 ; —SR 3 ; —(CH 2 ) p OR 3 ; —(CH 2 ) p SR 3 ; straight chained or branched C 1 -C 7  alkyl, aminoalkyl, carboxamidoalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl, or C 3 -C 7  cycloalkyl or cycloalkenyl; wherein the alkyl, aminoalkyl, carboxamidoalkyl, alkenyl, alkynyl, cycloalkyl or cycloalkenyl may be substituted with one or more aryl or heteroaryl, wherein the aryl or heteroaryl may be substituted with —F, —Cl, —Br, —I, —NO 2 , —CN, —OR 3 , —SR 3 , C 1 -C 3  alkyl, or carboxamido; aryl or heteroaryl, wherein the aryl or heteroaryl may be substituted with one or more —F, —Cl, —Br, —I, COR 3 , CO 2 R 3 , —CON(R 3 ) 2 , —CN, —NO 2 , —N(R 3 ) 2 , —OR 3 , —SR 3 , (CH 2 ) o OR 3 , (CH 2 ) o SR 3 ; straight chained or branched C 1 -C 7  alkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl, C 2 -C alkynyl, C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; and  
         wherein each R is independently —H; straight chained or branched C 1 -C 7  alkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, monofluoroalkyl or polyfluoroalkyl; straight chained or branched C 2 -C 7  alkenyl or alkynyl; C 3 -C 7  cycloalkyl, monofluorocycloalkyl, polyfluorocycloalkyl or cycloalkenyl; or —OR 4 ;  
         or a pharmaceutically acceptable salt thereof.  
       
     
     
         20 . A pharmaceutical composition comprising a therapeutically effective amount of the compound of  claim 1  and a pharmaceutically acceptable carrier.  
     
     
         21 . The pharmaceutical composition of  claim 20  wherein the amount of the compound is an amount from about 0.01 mg to about 500 mg.  
     
     
         22 . The pharmaceutical composition of  claim 21  wherein the amount of the compound is from about 0.1 mg to about 60 mg.  
     
     
         23 . The pharmaceutical composition of  claim 22  wherein the amount of the compound is from about 1 mg to about 20 mg.  
     
     
         24 . The pharmaceutical composition of  claim 20 , wherein the carrier is a liquid and the composition is a solution.  
     
     
         25 . The pharmaceutical composition of  claim 20 , wherein the carrier is a solid and the composition is a tablet.  
     
     
         26 . The pharmaceutical composition of  claim 20 , wherein the carrier is a gel and the composition is a suppository.  
     
     
         27 . The pharmaceutical composition of  claim 20 , wherein the compound additionally does not cause a fall in blood pressure at dosages effective to alleviate benign prostatic hyperplasia.  
     
     
         28 . A method of treating a subject suffering from benign prostatic hyperplasia which comprises administering to the subject an amount of the compound of  claim 1  effective to treat benign prostatic hyperplasia.  
     
     
         29 . A method of  claim 28 , wherein the compound additionally does not cause a fall in blood pressure at dosages effective to alleviate benign prostatic hyperplasia.  
     
     
         30 . The method of  claim 29 , wherein the compound effects treatment of benign prostatic hyperplasia by relaxing lower urinary tract tissue.  
     
     
         31 . The method of  claim 30 , wherein lower urinary tract tissue is prostatic smooth muscle.  
     
     
         32 . A method of treating a subject suffering from high intraocular pressure which comprises administering to the subject an amount of the compound of  claim 1  effective to lower intraocular pressure.  
     
     
         33 . A method of treating a subject suffering from a disorder associated with high cholesterol which comprises administering to the subject an amount of the compound of  claim 1  effective to inhibit cholesterol synthesis.  
     
     
         34 . A method of treating a disease which is susceptible to treatment by antagonism of the α 1A  receptor which comprises administering to the subject an amount of the compound of  claim 1  effective to treat the disease.  
     
     
         35 . A method of treating a subject suffering from impotency which comprises administering to the subject an amount of the compound of  claim 1  effective to treat impotency.  
     
     
         36 . A method of treating a subject suffering from sympathetically mediated pain which comprises administering to the subject an amount of the compound of  claim 1  effective to treat sympathetically mediated pain.  
     
     
         37 . A method of treating a subject suffering from cardiac arrhythmia which comprises administering to the subject an amount of the compound of claim  1  effective to treat cardiac arrhythmia.  
     
     
         38 . A method of treating a subject suffering from benign prostatic hyperplasia which comprises administering to the subject an amount of the compound of  claim 1  effective to treat benign prostatic hyperplasia.  
     
     
         39 . The method of  claim 38 , wherein the compound effects treatment of benign prostatic hyperplasia by relaxing lower urinary tract tissue.  
     
     
         40 . The method of  claim 39 , wherein lower urinary tract tissue is prostatic smooth muscle.  
     
     
         41 . A method of treating a subject suffering from benign prostatic hyperplasia which comprises administering to the subject an amount of the compound of  claim 1  in combination with a 5 alpha-reductase inhibitor effective to treat benign prostatic hyperplasia.  
     
     
         42 . The method of  claim 41 , wherein the 5-alpha reductase inhibitor is finasteride.  
     
     
         43 . A method of treating a subject suffering from benign prostatic hyperplasia which comprises administering to the subject an amount of the compound of  claim 1  in combination with a 5 alpha-reductase inhibitor effective to treat benign prostatic hyperplasia.  
     
     
         44 . The method of  claim 43 , wherein the 5-alpha reductase inhibitor is finasteride.  
     
     
         45 . A pharmaceutical composition comprising a therapeutically effective amount of the compound of  claim 1  in combination with a therapeutically effective amount of finasteride and a pharmaceutically acceptable carrier.  
     
     
         46 . The pharmaceutical composition of  claim 45  wherein the compound is present in an amount from about 0.01 mg to about 500 mg and the therapeutically effective amount of the finasteride is about 5 mg.  
     
     
         47 . The pharmaceutical composition of  claim 46  wherein the compound is present in an amount from about 0.1 mg to about 60 mg and the therapeutically effective amount of finasteride is about 5 mg.  
     
     
         48 . The pharmaceutical composition of  claim 47  wherein the compound is present in an amount from about 1 mg to about 20 mg and the therapeutically effective amount of finasteride is about 5 mg.  
     
     
         49 . A method of relaxing lower urinary tract tissue which comprises contacting the lower urinary tract tissue with an amount of the compound of  claim 1  effective to relax lower urinary tract tissue.  
     
     
         50 . The method of  claim 49 , wherein the lower urinary tract tissue is prostatic smooth muscle.  
     
     
         51 . A method of relaxing lower urinary tract tissue in a subject which comprises administering to the subject an amount of the compound of  claim 1  effective to relax lower urinary tract tissue.  
     
     
         52 . The method of  claim 51 , wherein the lower urinary tract tissue is prostatic smooth muscle.