Azacyclic compounds

Abstract

Compounds and methods are provided for the treatment of disease conditions in which modification of serotonergic receptor activity has a beneficial effect. In the method, an effective amount of a compound is adminstered to a patient in need of such treatment.

1 . A compound of formula (I)  
       
         
           
           
               
               
           
         
         wherein  
         Z is  
         
           
             
             
                 
                 
             
           
         
         in which  
         R is a hydrogen, a cyclic or straight-chained or branched acyclic organyl group, a lower hydroxyalkyl group, a lower aminoalkyl group, or an aralkyl or heteroaralkyl group;  
         n is 0, 1, or 2;  
         X 1  is methylene, vinylene, or an NH or N(lower alkyl) group; and  
         X 2  is methylene, or, when X 1  is methylene or vinylene, X 2  is methylene or a bond; or when X 1  is methylene, X 2  is O, S, NH, or N(lower alkyl) or a bond;  
         Y 1  is methylene and Y 2  is methylene, vinylene, ethylene, propylene, or a bond; or  
         Y 1  is a bond and Y 2  is vinylene; or  
         Y 1  is ethylene and Y 2  is O, S, NH, or N(lower alkyl);  
         Ar 1  and Ar 2  independently are unsubstituted or substituted aryl or heteroaryl groups, provided that Ar 1  and Ar 2  are not simultaneously phenyl; and  
         W is oxygen or sulfur.  
       
     
     
         2 . A compound according to  claim 1 , wherein 
 Y 1  is methylene and Y 2  is a bond, methylene, ethylene, or vinylene; or    Y 1  is ethylene and Y 2  is O or S; and    X 1  is methylene and X 2  is a bond, methylene, O, or S; or    X 1  is NH or N(lower alkyl) and X 2  is methylene.    
     
     
         3 . A compound according to  claim 2 , wherein 
 Z is                          and W is oxygen.    
     
     
         4 . A compound according to  claim 3 , wherein 
 Ar 1  and Ar 2  independently are mono- or disubstituted phenyl groups.    
     
     
         5 . A compound according to  claim 4 , wherein 
 R is a hydrogen, a lower alkyl group, a cyclic organyl group, or a substituted or unsubstituted aralkyl or heteroaralkyl group;    n is 1;    Y 1  is methylene, Y 2  is a bond, methylene, ethylene, or vinylene;    X 1  is methylene and X 2  is a bond, or.    X 1  is NH or N(lower alkyl) and X 2  is methylene; and    Ar 1  and Ar 2  are phenyl groups, independently p-substituted with groups selected from lower alkyl, lower alkoxy and halogen.    
     
     
         6 . A compound according to  claim 1 , having a formula (II)  
       
         
           
           
               
               
           
         
         wherein R N  is hydrogen, lower alkyl, aralkyl, or heteroaralkyl;  
         Ar L  is selected from lower alkyl, lower alkoxy and halogen  
         Ar R  is selected from lower alkyl, lower alkoxy and halogen;  
         k is 1 or  2 and A   −  is a suitable anion.  
       
     
     
         7 . The compound according to  claim 1 , wherein the compound is selected from the group consisting of: 
 N-(1-(1-methylethyl)piperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;    N-(1-(2,2-dimethylethyl)piperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;    N-(1-pentylpiperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;    N-(1-hexylpiperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;    N-(1-cyclohexylpiperidin-4-yl)-N-(4-methylphenyl)methyl)-4-methoxyphenylacetamide;    N-(1-cyclopentylpiperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;    N-(1-cyclobutylpiperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;    N-(1-cyclopropylpiperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;    N-(1-(cyclopentylmethyl)piperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;    N-(1-(cyclobutylmethyl)piperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;    N-(1-(cyclopropylmethyl)piperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;    N-(1-(2-hydroxyethyl)piperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;    N-(1-(3-hydroxypropyl)piperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;    N-((4-methylphenyl)methyl)-N-(piperidin-4-yl)-N]-phenylmethylcarbamide;    N-((4-methylphenyl)methyl)-N-(1-(2-methylpropyl)piperidin-4-yl)-N′-phenylmethylcarbamide;    N-(1-((2-bromophenyl)methyl)piperidin-4-yl)-N-((4-methylphenyl)methyl)-N-phenylmethylcarbamide;    N-(1-((4-hydroxy-3-methoxyphenyl)methyl)piperidin-4-yl)-N-((4-methylphenyl)methyl)-N′-phenylmethylcarbamide;    N-(1-((5-ethylthien-2-yl)methyl)piperidin-4-yl)-N-((4-methylphenyl)methyl)-N′-phenylmethylcarbamide;    N-(1-(imidazol-2-ylmethyl)piperidin-4-yl)-N-((4-methylphenyl)methyl)-N′-phenylmethylcarbamide;    N-(1-(cyclohexylmethyl)piperidin-4-yl)-N-((4-methylphenyl)methyl)-N′-phenylmethylcarbamide;    N-(1-((4-fluorophenyl)methyl)piperidin-4-yl)-N-((4-methylphenyl)methyl)-N′-phenylmethylcarbamide;    N-((4-methylphenyl)methyl)-N-(piperidin-4-yl)-4-methoxyphenylacetamide;    N-((4-methylphenyl)methyl)-N-(1-methylpiperidin-4-yl)-4-methoxyphenylacetamide;    N-(1-ethylpiperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;    N-((4-methylphenyl)methyl)-N-(1-propylpiperidin-4-yl)-4-methoxyphenylacetamide;    N-(1 butylpiperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;    N-(1-(3,3-dimethylbutyl)piperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;    N-(1-(cyclohexylmethyl)piperidin-4-yl)-N-((4-methylphenyl)methyl)-4-methoxyphenylacetamide;    N-((4-methylphenyl)methyl)-N-(1-(2-methylpropyl)piperidin-4-yl)-4-methoxyphenylacetamide;    N-((4-methylphenyl)methyl)-N-(1-((4-methylphenyl)methyl)piperidin-4-yl)-4-methoxyphenylacetamide;    N-(1-((4-hydroxyphenyl)methyl)piperidin-4-yl)-N-(4-methylphenyl)methyl)-4-methoxyphenylacetamide;    N-(1-((2-hydroxyphenyl)methyl)piperidin-4-yl)-N-(4-methylphenyl)methyl)-4-methoxyphenylacetamide;    N-(3-phenylpropyl)-N-(piperidin-4-yl)-4-methoxyphenylacetamide;    N-(2-phenylethyl)-N-(piperidin-4-yl)-4-methoxyphenylacetamide;    N-((2-methoxyphenyl)methyl)-N-(piperidin-4-yl)-4-methoxyphenylacetamide;    N-((2-chlorophenyl)methyl)-N-(piperidin-4-yl)-4-methoxyphenylacetamide;    N-((3,4-di-methoxyphenyl)methyl)-N-(piperidin-4-yl)-4-methoxyphenylacetamide;    N-((4-fluorophenyl)methyl)-N-(piperidin-4-yl)-4-methoxyphenylacetamide;    N-((2,4-di-chlorophenyl)methyl)-N-(piperidin-4-yl)-4-methoxyphenylacetamide;    N-((3-methylphenyl)methyl)-N-(piperidin-4-yl)-4-methoxyphenylacetamide;    N-((3-bromophenyl)methyl)-N-(piperidin-4-yl)-4-methoxyphenylacetamide;    N-(1-(phenylmethyl)piperidin-4-yl)-N-(3-phenyl-2-propen-1-yl)-4-methoxyphenylacetamide;    N-((4-methylphenyl)methyl)-N-(1-piperidin-4-yl)-phenylacetamide;    N-((4-methylphenyl)methyl)-N-(1-piperidin-4-yl)-3-phenylpropionamide;    N-((4-methylphenyl)methyl)-N-(1-piperidin-4-yl)-(phenylthio)acetamide;    N-((4-methylphenyl)methyl)-N-(1-piperidin-4-yl)-phenoxyacetamide;    N-((4-methylphenyl)methyl)-N-(1-piperidin-4-yl)-(4-chlorophenoxy)acetamide;    N-(4-methylphenyl)methyl)-N-(1-piperidin-4-yl)-3-methoxyphenylacetamide;    N-((4-methylphenyl)methyl)-N-(1-piperidin-4-yl)-4-fluorophenylacetamide;    N-((4-methylphenyl)methyl)-N-(1-piperidin-4-yl)-2,5-di-methoxyphenylacetamide;    N-((4-methylphenyl)methyl)-N-1-piperidin-4-yl)-4chlorophenylacetamide;    N-((4-methylphenyl)methyl)-N-(1-(phenylmethyl)pyrrolidin-3-yl)-N′-phenylmethylcarbamide;    N-((4-methylphenyl)methyl)-N-(1-(phenylmethyl)pyrrolidin-3-yl)-4-methoxyphenylacetamide;    2-(4-methoxyphenyl)-N-4-methylbenzyl)-N-(piperidin-4-yl)acetamide;    2-(4-methoxyphenyl)-N-(4-methylbenzyl)-N-(1-methylpiperidin-4-yl) acetamide;    2-(4-methoxyphenyl)-N-4-methylbenzyl)-N-(1-ethylpiperidin-4-yl) acetamide;    2-(4-methoxyphenyl)-N-(4-chlorbenzyl)-N-(1-ethylpiperidin-4-yl)acetamide.    2-(4-methoxyphenyl)-N-(4-chlorbenzyl)-N-(1-isopropylpiperidin-4-yl) acetamide;    2-(4-methoxyphenyl)-N-4-chlorobenzyl)-N-(piperidin-4-yl)acetamide;    2-(4-methoxyphenyl)-N-4-chlorbenzyl)-N-(1-cyclopentylpiperidin-4-yl) acetamide;    2-(4-methoxyphenyl)-N-(4-chlorbenzyl)-N-(1-isopropylpiperidin-4-yl) acetamide;    2-(phenyl)-N-(4-trifluoromethylbenzyl)-N-(1-methylpiperidin-4-yl)acetamide;    2-(4-fluorophenyl)-N-(4trifluoromethylbenzyl)-N-(1-methylpiperidin-4-yl) acetamide;    2-(4-Methoxyphenyl)-N-(4-trifluoromethylbenzyl)-N-(1-methylpiperidin-4-yl) acetamide;    2-(4-Trifluoromethylphenyl)-N-(4-trifluoromethylbenzyl)-N-(1-methylpiperidinyl)acetamide;    2-(4-Fluorophenyl)-N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)acetamide;    2-(4-Methoxyphenyl)-N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl) acetamide;    2-(phenyl)-N-(4-fluorobenzyl)-N-((1-methylpiperidin-4-yl)acetamide;    2-(4-Trifluoromethylphenyl)-N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl) acetamide;    2-(4-trifluoromethylphenyl)-N-[4methoxycarbonyl)benzyl]-N-(1-methylpiperidin-4-yl)acetamide;    2-Phenyl-N-[4-(methoxycarbonyl)benzyl]-N-(1-methylpiperidin-4-yl) acetamide;    2-(4-Chlorophenyl)-N-[4-(methoxycarbonyl)benzyl]-N-(1-methylpiperidin-4-yl)acetamide;    2-(4-Methoxyphenyl)-N-[4-(methoxycarbonyl)benzyl]-N-(1-methylpiperidin-4-yl)acetamide;    2-(4-trifluoromethylphenyl)-N-[4-(methoxycarbonyl)benzyl]-N-(1-methylpiperidin-4-yl)acetamide;    2-Phenyl-N-[4-(methoxycarbonyl)benzyl]-N-(1-methylpiperidin-4-yl) acetamide,    2-(4Chlorophenyl)-N-[4-(methoxycarbonyl)benzyl]-N-(1-methylpiperidin-4-yl)acetamide;    2-(4-Methoxyphenyl)-N-[4-(methoxycarbonyl)benzyl]-N-(1-methylpiperidin-4-yl)acetamide;    2-(4methoxyphenyl)-N-(4-methylbenzyl)-N-[1-(4-chloromethyl-2-thiazolylmethyl)piperidin-4-yl]acetamide;    2-(4 methoxyphenyl)-N-(4-methylbenzyl)-N-{1-[3-(1,3 dihydro-2H-benzimidazol-2-on-1-yl)propyl]piperidin-4-yl}acetamide;    2-(4-methoxyphenyl)-N-(2-4-(fluorophenyl)ethyl)-N-(1-methylpiperidin-4-yl) acetamide;    2-(4-methoxyphenyl)-N-[2-(2,5-dimethoxyphenyl)ethyl]-N-(1-methylpiperidin-4-yl)acetamide;    2-(4-methoxyphenyl)-N-[2-(2,4-dichlorophenyl)ethyl]-N-(1-methylpiperidin-4-yl)acetamide;    2-(4-methoxyphenyl)-N-[2-(3-chlorophenyl)ethyl]-N-(1-methylpiperidin-4-yl) acetamide;    2-(4-methoxyphenyl)-N-[2-(4-methoxyphenyl)ethyl]-N-(1-methylpiperidin-4-yl)acetamide;    2-(4-methoxyphenyl)-N-[2-(3-fluorophenyl)ethyl]-N-(1-methylpiperidin-4-yl) acetamide;    2-(4-ethoxyphenyl)-N-[2-(4-fluorophenethyl]-N-(1-methylpiperidin-4-yl) acetamide;    2-(4-ethoxyphenyl)-N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl)acetamide;    2-(4-methoxyphenyl)-N-(4-methylbenzyl)-N-{1 [22-hydroxyethoxy)ethyl]piperidin-4-yl}acetamide;    2-(4-methoxyphenyl)-N-(4-methylbenzyl)-N-[1-((2-chloro-5-thienyl)methyl) piperidin-4-yl]acetamide;    2-(4-methoxyphenyl)-N-(4-methylbenzyl)-N-[1-(2-(imidazolidinon-1-yl)ethyl)piperidin-4-yl]acetamide;    2-(4-methoxyphenyl)-N-(4-methylbenzyl)-N-{1-[2-(2,4-(1H,3H)quinazolinedion-3-yl)ethyl]piperidin-4-yl}acetamide;    2-(4-methoxyphenyl)-N-(4-methylbenzyl)-N-{1-[2-(1,3-dioxolan-2-yl)ethyl]piperidin-4-yl}acetamide;    2-(4-methoxyphenyl)-N-(4-methylbenzyl)-N-{1-[2-(3-indolyl)ethyl]piperidin-4-yl}acetamide;    2-(4-methoxyphenyl)-N-(4-methylbenzyl)-N-(1-[3-(1,2,4-triazol-1-yl)propyl]piperidin-4-yl)acetamide;    2-(4-methoxyphenyl)-N-(4-methylbenzyl)-N-[1-(5-benzofurazanylmethyl)piperidin-4-yl]acetamide;    2-(4-methoxyphenyl)-N-(4-methylbenzyl)-N-[1-(5-chlorobenzo[b]thien-3-ylmethyl)piperidin-4-yl]acetamide;    2-(4-methoxyphenyl)-N-(4-methylbenzyl)-N-[1-(5-phenyl-1,2,4-oxadiazol-3-ylmethyl)piperidin-4-yl]acetamide;    2-(4-Chlorophenyl)-N-(4-methylbenzyl)-N-(1-isopropylpiperidin-4-yl)acetamide;    2-(4-Chlorophenyl)-N-4-methylbenzyl)-N-(1-ethylpiperidin-4-yl)-acetamide;    2-Phenyl-N-(4-methylbenzyl)-N-(1-methylpiperidin-4-yl)-acetamide,2-(4-Chlorophenyl)-N-(4-methylbenzyl)-N-(1-methylpiperidin-4-yl)-acetamide;    2-(4-Chlorophenyl)-N-4-methylbenzyl)-N-(1-cyclopentylpiperidin-4-yl)acetamide;    2-(4-Fluorophenyl)-N-(4-methylbenzyl)-N-(1-methylpiperidin 4-yl)acetamide;    2-(4-Chlorophenyl)-N-(4-methylbenzyl)-N-(1-(2-hydroxyethyl)-piperidin-4-yl)-acetamide;    2-(4-Chlorophenyl)-N-(4-methylbenzyl)-N-(1-cyclobutylpiperidin-4-yl)acetamide;    2-(4-Methoxyphenyl)-N-(4-methylbenzyl)-N-(1-cyclobutylpiperidin-4-yl)acetamide,2-(4-Methoxyphenyl)-N-(4-methylbenzyl)-N-(tropin-4-yl)-acetamide;    N-(4-Methylbenzyl)-N-(1-methylpiperidin-4-yl)-N′-benzyl-carbamide;    N-(4-Methylbenzyl)-N-(1-methylpiperidin-4-yl)-N′-phenyl-carbamide;    N-Phenethyl-N-(1-methylpiperidin-4-yl)-N′-benzyl-carbamide;    2-Phenyl-N-(4-methoxybenzyl)-N-(1-methylpiperidin-4-yl)-acetamide;    2-(4-Trifluoromethylphenyl)-N-(4-methoxybenzyl)-N-(1-methylpiperidin-4-yl)-acetamide;    2-(4-Fluorophenyl)-N-(4-methoxybenzyl)-N-(1-methylpiperidin-4-yl)acetamide;    2-(4-Methoxyphenyl)-N-(4-methoxybenzyl)-N-(1-methylpiperidin-4-yl)acetamide;    2-(4-Methylphenyl)-N-(4-chlorobenzyl)-N-(1-methylpiperidin-4-yl)acetamide;    2-(4-Hydroxyphenyl)-N-(4-methylbenzyl)-N-(1-methylpiperidin-4-yl)acetamide;    N-Phenethyl-N-(1-methylpiperidin-4-yl)-N′-phenyl-carbamide;    N-(3-Phenylpropyl)-N-1-methylpiperidin-4-yl)-N′-benzyl-carbamide;    N-(3-Phenylpropyl)-N-(1-methylpiperidin-4-yl)-N′-phenyl-carbamide;    2-(4-Methoxyphenyl)-2,2-ethylene-N-(4-methylbenzyl)-N-(1-methylpiperidin-4-yl)acetamide;    2-(4-Methoxyphenyl)-N-alpha-methylbenzyl-N-(1-methylpiperidin-4-yl) acetamide;    2-(4-Methoxyphenyl)-N-(4-methylbenzyl)-N-(3-tropen-4-yl)acetamide;    2-Phenyl-2-ethyl-N-(4-methylbenzyl)-N-(1-methylpiperidin-4-yl)acetamide;    N-Phenethyl-N-(4-methylbenzyl)-N-(1-methylpiperidin-4-yl)-amine;    2-(4-Methoxyphenyl)-N-(1-indanyl)-N-(1-methylpiperidin-4-yl)acetamide;    N-(4-Methylbenzyl)-N-(1-methylpiperidin-4-yl)-N′-(4-methoxybenzyl)carbamide;    2-(3,4-dimethoxyphenyl)-N-(4-methylbenzyl)-N-(1-methylpiperidin-4-yl) acetamide;    2-(3,4-Methylenedioxyphenyl)-N-(4-methylbenzyl)-N-(1-methylpiperidin-4-yl)acetamide;    2-(4-Methoxyphenyl)-N-4-methylbenzyl)-N-(1-t-butylpiperidin-4-yl)acetamide;    N-(4-Methylbenzyl)-N-(1-methylpiperidin-4-yl)-N′-phenethyl-carbamide;    N-Phenethyl-N-(1-methylpiperidin-4-yl)-N′-phenethyl-carbamide;    N-(4-Methylbenzyl)-N 1-t-butylpiperidin-4-yl)-N′-(4-methoxybenzyl)carbamide;    2-(4-Ethoxyphenyl)-N-(4-methylbenzyl)-N-(1-methylpiperidin-4-yl) acetamide;    2-(4-Butoxyphenyl)-N-(4-methylbenzyl)-N-(1-methylpiperidin-4-yl) acetamide;    2-(4-i-Propoxyphenyl)-N-(4-methylbenzyl)-N-(1-methylpiperidin-4-yl) acetamide;    2-(4-t-Butoxyphenyl)-N-4-methylbenzyl)-N-(1-methylpiperidin-4-yl) acetamide;    2-(4-Butoxyphenyl)-N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl) acetamide;    2-(4-Propoxyphenyl)-N-(4-flourobenzyl)-N-(1-methylpiperidin-4-yl) acetamide;    2-(4-i-Propoxyphenyl)-N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl) acetamide; and    2-(4-t-Butoxyphenyl)-N-(4-fluorobenzyl)-N-(1-methylpiperidin-4-yl) acetamide.    
     
     
         8 . A compound of formula (I)  
       
         
           
           
               
               
           
         
         wherein  
         Z is  
         
           
             
             
                 
                 
             
           
         
         in which  
         R is a hydrogen, a cyclic or straight-chained or branched acyclic organyl group, a lower hydroxyalkyl group, a lower aminoalkyl group, or an aralkyl or heteroaralkyl group; and  
         n is 0, 1, or 2;  
         X 1  is methylene, vinylene, or an NH or N(lower alkyl) group; and  
         X 2  is methylene, or, when X 1  is methylene or vinylene, X 2  is methylene or a bond; or when X 1  is methylene, X 2  is O, S, NH, or N(lower alkyl) or a bond;  
         Y 1  is methylene and Y 2  is methylene, vinylene, ethylene, propylene, or a bond; or  
         Y 1  is a bond and Y 2  is vinylene; or  
         Y 1  is ethylene and Y 2  is O, S, NH, or N(lower alkyl);  
         Ar 1  and Ar 2  are different unsubstituted or substituted aryl or heteroaryl groups; and  
         W is oxygen or sulfur.  
       
     
     
         9 . A compound according to  claim 8 , wherein 
 Y 1  is methylene and Y 2  is a bond, methylene, ethylene, or vinylene; or    Y 1  is ethylene and Y 2  is O or S; and    X 1  is methylene and X 2  is a bond, methylene, O, or S; or    X 1  is NH or N(lower alkyl) and X 2  is a methylene.    
     
     
         10 . A compound according to  claim 9 , wherein 
 Z is                          and W is oxygen.    
     
     
         11 . A compound according to  claim 10 , wherein 
 Ar 1  and Ar 2  independently are mono- or disubstituted phenyl groups.    
     
     
         12 . A compound according to  claim 11 , wherein 
 R is a hydrogen, a lower alkyl group, a cyclic organyl group, or an, optionally substituted, alalkyl or heteroaralkyl group;    n is 1;    Y 1  is methylene, Y 2  is a bond, methylene, ethylene, or vinylene;    X 1  is methylene and X 2  is a bond, or    X 1  is NH or N(lower alkyl) and X 2  is methylene; and    Ar 1  and Ar 2  are phenyl groups, independently p-substituted with groups selected from alkyl, lower alkoxy and halogen.    
     
     
         13 . A compound according to  claim 7 , having a formula (II):  
       
         
           
           
               
               
           
         
         wherein R N  is hydrogen, lower allyl, aralkyl, or heteroaralkyl;  
         Ar L  is selected from lower alkyl, lower alkoxy and halogen  
         Ar R  is selected from lower alkyl, lower alkoxy and halogen;  
         k is 1 or 2  
         and A −  is a suitable anion.  
       
     
     
         14 . A pharmaceutical composition comprising an effective amount of a compound of formula (I):  
       
         
           
           
               
               
           
         
         wherein  
         Z is  
         
           
             
             
                 
                 
             
           
         
         in which  
         R is a hydrogen, a cyclic or straight-chained or branched acyclic organyl group, a lower hydroxyalkyl group, a lower aminoalkyl group, or an aralkyl or heteroaralkyl group; and  
         n is 0, 1, or 2;  
         X 1  is methylene, vinylene, or an NH or N(lower alkyl) group; and  
         X 2  is methylene, or, when X 1  is methylene or vinylene, X 2  is methylene or a bond; or when X 1  is methylene, X 2  is O, S, NH, or N(lower alkyl) or a bond;  
         Y 1  is methylene and Y 2  is methylene, vinylene, ethylene, propylene, or a bond; or  
         Y 1  is a bond and Y 2  is vinylene; or  
         Y 1  is ethylene and Y 2  is O, S, NH, or N(lower alkyl);  
         Ar 1  and Ar 2  independently are unsubstituted or substituted aryl or heteroaryl groups, provided that Ar 1  and Ar 2  are not simultaneously phenyl; and  
         W is oxygen or sulfur;  
         or a pharmaceutically acceptable salt, ester or prodrug thereof, and  
         a pharmaceutically acceptable diluent or excipient.  
       
     
     
         15 . A method of inhibiting an activity of a monoamine receptor comprising contacting the monoamine receptor or a system containing the monoamine receptor with an amount of one or more of the compounds of  claim 1  that is effective in inhibiting the activity of the monoamine receptor.  
     
     
         16 . The method of  claim 15  wherein the monoamine receptor is a serotonin receptor.  
     
     
         17 . The method of  claim 16  wherein the serotonin receptor is the 5-HT2A subclass.  
     
     
         18 . The method of  claim 16  wherein the serotonin receptor is in the central nervous system.  
     
     
         19 . The method of  claim 16  wherein the serotonin receptor is in the peripheral nervous system.  
     
     
         20 . The method of  claim 16  wherein the serotonin receptor is in blood cells or platelets.  
     
     
         21 . The method of  claim 16  wherein the serotonin receptor is mutated or modified.  
     
     
         22 . The method of  claim 15  wherein the activity is signaling activity.  
     
     
         23 . The method of claim  1 S wherein the activity is constitutive.  
     
     
         24 . The method of  claim 15  wherein the activity is associated with serotonin receptor activation.  
     
     
         25 . A method of inhibiting an activation of a monoamine receptor comprising contacting the monoamine receptor or a system containing the monoamine receptor with an amount of a compound of one or more of the compounds of  claim 1  that is effective in inhibiting the activation of the monoamine receptor.  
     
     
         26 . The method of  claim 25  wherein the activation is by an agonistic agent.  
     
     
         27 . The method of  claim 26  wherein the agonistic agent is exogenous.  
     
     
         28 . The method of  claim 26  wherein the agonistic agent is endogenous.  
     
     
         29 . The method of  claim 25  wherein the activation is constitutive.  
     
     
         30 . The method of  claim 25  wherein the monoamine receptor is a serotonin receptor.  
     
     
         31 . The method of  claim 30  wherein the serotonin receptor is the 5-HT2A subclass.  
     
     
         32 . The method of  claim 30  wherein the serotonin receptor is in the central nervous system.  
     
     
         33 . The method of  claim 30  wherein the serotonin receptor is in the peripheral nervous system.  
     
     
         34 . The method of  claim 30  wherein the serotonin receptor is in blood cells or platelets.  
     
     
         35 . The method of  claim 30  wherein the serotonin receptor is mutated or modified.  
     
     
         36 . A method of treating a disease condition associated with a monoamine receptor comprising administering to a subject in need of such treatment a therapeutically effective amount of one or more of the compounds of  claim 1 .  
     
     
         37 . The method of  claim 36  wherein the disease condition is selected from the group consisting of schizophrenia, psychosis, migraine, hypertension, thrombosis, vasospasm, ischemia, depression, anxiety, sleep disorders and appetite disorders.  
     
     
         38 . The method of  claim 36  wherein the disease condition is associated with dysfunction of a monoamine receptor.  
     
     
         39 . The method of  claim 36  wherein the disease condition is associated with activation of a monoamine receptor.  
     
     
         40 . The method of  claim 36  wherein the disease condition is associated with increased activity of monoamine receptor.  
     
     
         41 . The method of  claim 36  wherein the monoamine receptor is a serotonin receptor  
     
     
         42 . The method of  claim 41  wherein the serotonin receptor is the 5-HT2A subclass.  
     
     
         43 . The method of  claim 41  wherein the serotonin receptor is in the central nervous system.  
     
     
         44 . The method of  claim 41  wherein the serotonin receptor is in the peripheral nervous system.  
     
     
         45 . The method of  claim 41  wherein the serotonin receptor is in blood cells or platelets.  
     
     
         46 . The method of  claim 41  wherein the serotonin receptor is mutated or modified.  
     
     
         47 . A method of treating schizophrenia comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound of one or more of the compounds of  claim 1 .  
     
     
         48 . A method of treating migraine comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound of one or more of the compounds of  claim 1 .  
     
     
         49 . A method of treating psychosis comprising administering to a subject in need of such treatment a therapeutically effective amount of a compound of one or more of the compounds of  claim 1 .  
     
     
         50 . A method for identifying a genetic polymorphism predisposing a subject to being responsive to one or more of the compounds of  claim 1 , comprising: 
 administering to a subject a therapeutically effective amount of the compound;    measuring the response of said subject to said compound, thereby identifying a responsive subject having an ameliorated disease condition associated with a monoamine receptor, and    identifying a genetic polymorphism in the responsive subject, wherein the genetic polymorphism predisposes a subject to being responsive to the compound.    
     
     
         51 . The method of  claim 50  wherein the ameliorated disease condition is associated with the 5-HT class or 5-HT2A subclass of monoaminergic receptors.  
     
     
         52 . A method for identifying a subject suitable for treatment with one or more of the compounds of  claim 1 , comprising detecting the presence of a polymorphism in a subject wherein the polymorphism predisposes the subject to being responsive to the compound, and wherein the presence of the polymorphism indicates that the subject is suitable for treatment with one or more of the compounds of  claim 1.