1,4-piperazine derivatives

Abstract

Compounds of the formula are useful for the treatment of disorder of the central nervous system including anxiety, depression, panic, alcohol and drug addiction, sexual dysfunction, sleep disorders, cognitive disorders, Alzheimer's disease and Parkinson's disease.

What is claimed is:  
     
         1 . A compound of formula (A),  
                   
       in which: 
 R1 is aryl or heteroaryl;  
 A is NR2 or CH2 and B is N, NR2 or CH2, provided that A is not equal to B;  
 R2 is hydrogen, alkyl, cycloalkyl, alkylcycloalkyl, heterocycloalkyl, alkylheterocycloalkyl, aryl, aralkyl, heteroaryl, alkylheteroaryl, or COR3;  
 R3 is hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;  
 n is an integer from 0 to 2, or a pharmaceutical salt thereof.  
 
     
     
         2 . A compound of    claim 1    wherein R1 is phenyl; 2-, 3- or 4-pyridyl; 2-pyrimidyl; benzodioxan-5-yl; indol-4-yl; 3 -thienyl; 1-, or 2-naphthyl.  
     
     
         3 . A compound of    claim 1    wherein R1 is phenyl or indol-4-yl.  
     
     
         4 . A compound of    claim 1    wherein R2 is aralkyl, alkylcycloalkyl, alkylheteroaryl, alkylheterocycloalkyl or COR3.  
     
     
         5 . A compound of    claim 1    wherein R1 is phenyl or indol-4-yl, R2 is COR3 and R3 is cyclohexyl, phenyl or piperadin-4-yl.  
     
     
         6 . A compound of    claim 1    which is 1-(2-Methoxy-phenyl)-4-piperidin-4-ylmethyl-piperazine, or a pharmaceutical salt thereof.  
     
     
         7 . A compound of    claim 1    which is Cyclohexyl-{4-[4-(2-methoxy-phenyl)-piperazin-1-ylmethyl]-piperidin-1-yl}-methanone, or a pharmaceutical salt thereof.  
     
     
         8 . A compound of    claim 1    which is 1-(1-Cyclohexylmethyl-piperidin-3-ylmethyl)-4-(2-methoxy-phenyl)-piperazine, or a pharmaceutical salt thereof.  
     
     
         9 . A compound of    claim 1    which is {4-[4-(2-Methoxy-phenyl)-piperazin-1-ylmethyl]-piperidin-1-yl}-phenyl-methanone, or a pharmaceutical salt thereof.  
     
     
         10 . A compound of    claim 1    which is 1-(1-Benzyl-piperidin-4-ylmethyl)-4-(2-methoxy-phenyl)-piperazine, or a pharmaceutical salt thereof.  
     
     
         11 . A compound of    claim 1    which is 1-(2-Methoxy-phenyl)-4-piperidin-3-ylmethyl-piperazine, or a pharmaceutical salt thereof.  
     
     
         12 . A compound of    claim 1    which is Cyclohexyl-{3-[4-(2-methoxy-phenyl)-piperazin-1-ylmethyl]-piperidin-1-yl}-methanone, or a pharmaceutical salt thereof.  
     
     
         13 . A compound of    claim 1    which is {3-[4-(2-Methoxy-phenyl)-piperazin-1-ylmethyl]-piperidin-1-yl}-phenyl-methanone, or a pharmaceutical salt thereof.  
     
     
         14 . A compound of    claim 1    which is 1-(1-Benzyl-piperidin-3-ylmethyl)-4-(2-methoxy-phenyl)-piperazine, or a pharmaceutical salt thereof.  
     
     
         15 . A compound of    claim 1    which is 3-(2-{3-[4-(2-Methoxy-phenyl)-piperazin-1-ylmethyl]-piperidin-1-yl}-ethyl)-1H-indole, or a pharmaceutical salt thereof.  
     
     
         16 . A compound of    claim 1    which is [4-(1H-Indol-4-yl)-piperazin-1-yl]-piperidin-4-yl-methanone, or a pharmaceutical salt thereof.  
     
     
         17 . A compound of    claim 1    which is 4-[4-(1-Methyl-piperidin-4-ylmethyl)-piperazin-1-yl]-1H-indole, or a pharmaceutical salt thereof.  
     
     
         18 . A method of treating a patient suffering from a disorder of the central nervous system associated with the 5-hydroxytryptamine 1A receptor subtype comprising administering a therapeutically effective amount of a compound of Formula A,  
                   
       in which: 
 R1 is aryl or heteroaryl;  
 A is NR2 or CH2 and B is N, NR2 or CH2, provided that A is not equal to B;  
 R2 is hydrogen, alkyl, cycloalkyl, alkylcycloalkyl, heterocycloalkyl, alkylheterocycloalkyl, aryl, aralkyl, heteroaryl, alkylheteroaryl, or COR3;  
 R3 is hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl;  
 n is an integer from 0 to 2, or a pharmaceutical salt thereof.  
 
     
     
         19 . The method of    claim 18    wherein the disorder is depression, anxiety or panic.  
     
     
         20 . The method of    claim 18    wherein the disorder is sleep disorder or sexual dysfunction.  
     
     
         21 . The method of    claim 18    wherein the disorder is drug or alcohol addiction.  
     
     
         22 . The method of    claim 18    wherein the disorder is a cognitive disorder.  
     
     
         23 . The method of    claim 18    wherein the disorder is a neurodegenerative disease.  
     
     
         24 . The method of    claim 23    wherein the neurodegenerative diseases is Parkinson's disease or Alzheimer's disease.  
     
     
         25 . The method of    claim 18    wherein the disorder is migraine.  
     
     
         26 . The method of    claim 18    wherein the disorder is obesity.  
     
     
         27 . The method of    claim 18    further comprising administration of a serotonin reuptake inhibitor.  
     
     
         28 . The method of    claim 27    wherein the serotonin reuptake inhibitor is selected from the group consising of fluoxetine, fluvoxamine, paroxetine, sertraline and venlafaxine.