N-substituted imide derivatives with serotonergic activity

Abstract

Compounds of the Formula (I) wherein R 2 , Y, X and n are as defined in the specification which compounds are useful in the treatment of disorders associated with serotonergic neuron-related diseases.

What is claimed is:  
     
         1 . A compound having the Formula (I)  
       
         
           
           
               
               
           
         
       
       wherein: 
 n is an integer of 0 to 5;  
 X is a moiety selected from the group consisting of:  
                     
 Y is a moiety selected from the group consisting of:  
                     
 R 1  is aryl of 6 to 12 carbon atoms optionally substituted with one or more substituents selected from alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, hydroxy, alkoxy of 1 to 10 carbon atoms, perhaloalkyl of 1 to 10 carbon atoms, perhaloalkoxy of 1 to 10 carbon atoms, —CN, —NO 2 , and halogen; heteroaryl having 5 or 6 ring atoms containing 1 to 3 heteroatoms which may be the same or different, selected from nitrogen, oxygen and sulfur, optionally substituted with 1 to 3 substituents which may be the same or different selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO 2 , and halogen; bicyclic heteroaryl having 8 to 20 ring atoms containing 1 to 3 heteroatoms which may be the same or different selected from nitrogen, oxygen and sulfur optionally substituted with 1 to 3 substituents which may be the same or different, selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO 2 , and halogen;  
 R 2  is independently H, alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, alkoxy of 1 to 10 carbon atoms, hydroxy, —(CH 2 ) z -O-alkyl of 1 to 6 carbon atoms, —(CH 2 ) z -S-alkyl of 1 to 6 carbon atoms, —(CH 2 ) z OH, perhaloalkyl of 1 to 10 carbon atoms, perhaloalkoxy of 1 to 10 carbon atoms, —CN, —NO 2 , and halogen; aryl of 6 to 12 carbon atoms optionally substituted with one or more substituents selected from alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, hydroxy, alkoxy of 1 to 10 carbon atoms, perhaloalkyl of 1 to 10 carbon atoms, perhaloalkoxy of 1 of to 10 carbon atoms, —CN, —NO 2 , and halogen; heteroaryl having 5 or 6 ring atoms containing 1 to 3 heteroatoms which may be the same or different, selected from nitrogen, oxygen and sulfur, optionally substituted with 1 to 3 substituents which may be the same or different selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO 2 , and halogen; bicyclic heteroaryl having 8 to 20 ring atoms containing 1 to 3 heteroatomns which may be the same or different selected from nitrogen, oxygen and sulfur optionally substituted with 1 to 3 substituents which may be the same or different, selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO 2 , and halogen;  
 z is an integer of 1 to 3;  
 R 3  is independently cycloalkyl or cycloalkenyl of 3 to 10 carbon atoms;  
 R 4  is aryl of 6 to 12 carbon atoms optionally substituted with one or more substituents selected from alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, hydroxy, alkoxy of 1 to 10 carbon atoms, perhaloalkyl of 1 to 10 carbon atoms, perhaloalkoxy of 1 to 10 carbon atoms, —CN, —NO 2 , and halogen; heteroaryl having 5 or 6 ring atoms containing 1 to 3 heteroatoms which may be the same or different, selected from nitrogen, oxygen and sulfur, optionally substituted with 1 to 3 substituents which may be the same or different selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO 2 , and halogen, bicyclic heteroaryl having 8 to 20 ring atoms containing 1 to 3 heteroatoms which may be the same or different selected from nitrogen, oxygen and sulfur optionally substituted with 1 to 3 substituents which may be the same or different, selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO 2 , and halogen;  
 with the proviso that X is not the radical  
                     
 when R 5  is H, halogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms and hydroxyl; n is 0; R 2  is H; Y is the radical  
                     
 and R 4  is phenyl substituted with three substituents which are the same or different selected from H, halogen, alkyl of 1 to 6 carbon atoms and alkoxy of 1 to 6 carbon atoms; or a pharmaceutically acceptable salt thereof.  
 
     
     
         2 . A compound according to  claim 1  wherein Y is the moiety  
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof.  
       
     
     
         3 . A compound according to  claim 1  wherein Y is the moiety  
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof.  
       
     
     
         4 . A compound according to  claim 1  wherein Y is the moiety  
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof.  
       
     
     
         5 . A compound according to  claim 1  wherein 
 R 1  is phenyl optionally substituted with one or two substituents selected from alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, perhaloalkyl of 1 to 10 carbon atoms, perhaloalkoxy of 1 to 10 carbon atoms, —CN, —NO 2 , and halogen; 2 or 3-furyl, 2 or 3-thienyl, 2,3- or 4-pyridyl; indolyl, azaindolyl, benzimidazolyl, indazolyl, quinolinyl, isoquinolinyl, benzodioxanyl, benzopyranyl, benzofuranyl, dihydrobenzofuranyl, benzothioplicnyl, benzothiazolyl, benzothiadiazolyl, benzooxazolyl and 2,3-dihydro-benzo[1,4]dioydn; or a pharmaceutically acceptable salt thereof.  
 
     
     
         6 . A compound according to  claim 1  wherein: 
 R 2  is selected from 1H, alkyl of 1 to 6 carbos atoms, cycloalkyl of 3 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, alkoxy of 1 to 10 carbon atoms, hydroxy, —(CH 2 ) z -O-alkyl of 1 to 6 carbon atoms, —(CH 2 ) z -S-alkyl of 1 to 6 carbon atoms, —(CH 2 ) z OH, perhaloalkyl of 1 to 10 carbon atoms, perhaloalkoxy of 1 to 10 carbon atoms, —CN, —NO 2 , and halogen; phenyl optionally substituted with 1 or 2 subtituents selected from alkyl of 1 to 6 carbon atoms, cycloalkyl of 1 to 6 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, hydroxy, alkoxy of 1 to 10 carbon atoms, perhaloalkyl of 1 to 10 carbon atoms, perhaloalkoxy of 1 to 10 carbon atoms, —CN, —NO 2 , and halogen; 2 or 3-furyl, 2 or 3-thienyl, 2-,3- or 4-pyridyl; indolyl, azaindolyl, benzimidazolyl, indazolyl, quinolinyl, isoquinolinyl, benzodioxanyl, benzopyranyl, benzofuranyl, diliydrobenzoforanyl, benzothiophenyl, benzothiazolyl, benzothiadiazolyl, benzooxazolyl and 2,3-dihydro-betizo[1,4]dioxin;  
 or a pharmaceutically acceptable salt thereof.  
 
     
     
         7 . A compound according to  claim 1  wherein X is the moiety  
       
         
           
           
               
               
           
         
         Y is the moiety  
         
           
             
             
                 
                 
             
           
         
         or a pharmaceutically acceptable salt thereof.  
       
     
     
         8 . A compound according to  claim 1  wherein X is the moiety Y is the moiety  
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof.  
       
     
     
         9 . A compound according to  claim 1  wherein X is the moiety  
       
         
           
           
               
               
           
         
         Y is the moiety  
         or a pharmaceutically acceptable salt thereof.  
       
     
     
         10 . A compound according to  claim 1  wherein X is the moiety  
       
         
           
           
               
               
           
         
         Y is the moiety  
         
           
             
             
                 
                 
             
           
         
         R 1  is phenyl optionally substituted with one or two substituents selected front alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, hydroxy, alkoxy of 1 to 10 carbon atoms, perhaloalkyl of 1 to 10 carbon atoms, perhaloalkoxy of 1 to 10 carbon atoms, —CN, —NO 2 , and halogen; indolyl and 2,3-dihydro-benzo[1,4]dioxin;  
         or a pharmaceutically acceptable salt thereof.  
       
     
     
         11 . A compound according to  claim 1  wherein X is the moiety Y is the moiety  
       
         
           
           
               
               
           
         
         R 1  is phenyl optionally substituted with one or two substituents selected from alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, hydroxy, alkoxy of 1 to 10 carbon atoms, perhaloalkyl of 1 to 10 carbon atoms, perhaloalkoxy of 1 to 10 carbon atoms, —CN, —NO 2 , and halogen; indolyl and 2,3-dihydro-benzo[1,4]dioxin;  
         R 4  is phenyl, optionally substituted with one, two or three substituents selected from alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, hydroxy, alkoxy of 1 to 10 carbon atoms, perhaloalkyl of 1 to 10 carbon atoms, perhaloakoxy of 1 to 10 carbon atoms,  
         —CN, —NO 2 , and halogen;  
         or a pharmaceutically acceptable salt thereof.  
       
     
     
         12 . A compound according to  claim 1  wherein X is the moiety  
       
         
           
           
               
               
           
         
         R 1  is phenyl optionally substituted with one or two substituent selected alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, hydroxy, alkoxy of 1 to 10 carbon atoms, perhaloalkyl of 1 to 10 carbon atoms, perhaloalkoxy of 1 to 10 carbon atoms, —CN, —NO 2 , and halogen; indolyl and 2,3-dihydro-benzo[1,4]dioxin;  
         R 4  is phenyl, optionally substituted with one, two or three substituents selected from alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, hydroxy, alkoxy of 1 to 10 carbon atoms, perhaloalkyl of 1 to 10 carbon atoms, perhaloalkoxy of 1 to 10 carbon atoms, —CN, —NO 2 , and halogen;  
         
           
             
             
                 
                 
             
           
         
         Y is the moiety  
         or a pharmaceutically acceptable salt thereof.  
       
     
     
         13 . The compound of  claim 1  which is selected from the group consisting of cyclohexanecarboxylic acid cyclohexanecarbonyl-{2-[4-(2-methoxyphenyl)-piperazin-1-yl]ethyl}-amide dihydrocliloride, cyclolioxanearboxylic acid cyclohexanecarbonyl-{2-[4-(1H-indol-4-yl)-piperazin-1-yl]-ethyl}-amide dihydrochloride, cyclohexanecarboxylic acid cyclohexanecarbonyl-{2-[4-(2,3-dihydrobenzo[1,4-dioxin)-5-yl)-piperazin-1-yl]-ethyl}-amide sesquihydrochloride monolydrate,(R)-cyclohexanecarboxylic acid cyclohexanecarbonyl-{1-methyl-2-[4-(2-methoxyphenyl)-piperazin-1-yl]-ethyl}-amide furmarate,(R)-cyclohexanecarboxylic acid cyclohexanecarbonyl-{1-(4-benzyl)-2-[4(2-methoxy-phenyl)-piperazin-1-yl]-ethyl}-amide fumarate, 
 (R)-cyclohexanecarboxylic acid cyclohexanecarbonyl-{1-(4-methoxybenzyl)-2-[4-(2-methoxyphenyl)-piperazin-1-yl]-ethyl}-amide hydrochloride,  
 (R)-cyclohexanecarboxylic acid cyclohexanecarbonyl-{1-(2-methoxyphenyl)-piperazin-1-ylmethyl]-2-(1-methyl-1H-indol-3-yl)ethyl}-amide hydrochloride monohydrate,cyclohexanecarboxylic acid {2-[4]-(2,3-dihydro-benzo[1,4]dioxin-5-yl)-piperazin-1-yl-ethyl}-amide,cyclohexanecarboxylic acid benzoyl-{2-[4-(2,3-dihydro-benzo[1 ,4]dioxin-5-yl)-piperazin-1-ylethyl}-amide hydrochloride sesquihydrate,  
 N-benzoyl-N-{-2-(4-(2-methoxyphenyl)-piperaizin-1-yl]-ethyl}-benzamide hydrochloride hemihydrate, and  
 (R)-N-benzoyl-N-{1-methyl-2-[4(2-methoxyphenyl)-piperazin-1-yl]-ethyl}-benzamide semifumarate-hemihydrate;  
 or a pharmaceutically acceptable salt thereof.  
 
     
     
         14 . A pharmaceutical composition for treating disorders associated with serotonergic neuron-related diseases, which comprises administering to a mammal in need thereof an effective amount of a compound of Formula (I)  
       
         
           
           
               
               
           
         
       
       wherein: 
 n is an integer of 0 to 5;  
 X is a moiety selected from the group consisting of:  
                     
 Y is moiety selected from the group consisting of:  
                     
 R 1  is aryl of 6 to 12 carbon atones optionally substituted with one or more substituents selected from alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, hydroxy, alkoxy of 1 to 10 carbon atoms, perhaloalkyl of 1 to 10 carbon atoms, perhaloalkoxy of 1 to 10 carbon atoms, —CN, —NO 2 , and halogen, heteroaryl having 5 or 6 ring atoms containing 1 to 3 heteroatoms which may be the same or different, selected from nitrogen, oxygen and sulfur, optionally substituted with 1 to 3 substituents which may be the same or different selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO 2 , and halogen; bicyclic heteroaryl having 8 to 20 ring atoms containing 1 to 3 heteroatoms which may be the same or different selected from nitrogen, oxygen and sulfur optionally substituted with 1 to 3 substituents which may be the same or different, selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO 2 , and halogen;  
 R 2  is independently 4 alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkonyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, alkoxy of 1 to 10 carbon atoms, hydroxy, —CHO 2 ) z -O-alkyl of 1 o 6 carbon atoms , —(CH 2 ) z -S-alkyl of 1 to 6 carbon atoms, —(CH 2 ) z OH, perhaloalkyl of 1 to 10 carbon atoms, perhaloalkoxy of 1 to 10 carbon atoms, —CN, —NO 2 , and halogen; aryl of 6 to 12 carbon atoms optionally substituted with one or more substituents selected from alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, hydroxy, alkoxy of 1 to 10 carbon atoms, perhaloalkyl of 1 to 10 carbon atoms, perhaloalkxy of 1 to 10 carbon atoms, —CN,—NO 2 , and halogen; heteroaryl having 5 or 6 ring atoms containing 1 to 3 heteratoms which may be the same or different, selected from nitrogen, oxygen and sulfur, optionally substituted with 1 to 3 substituents which may be the same or different selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO 2 , and halogen; bicyclic heteroaryl having 8 to 20 ring atoms containing 1 to 3 heteroatoms which may be the same or different selected from nitrogen, oxygen and sulfur optionally substituted with 1 to 3 substituents which may be the saine or different, selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO 2 , and halogen;  
 z is an integer of 1 to 3;  
 R 3  is independently cycloalkyl or cycloalkenyl of 3 to 10 carbon atoms;  
 R 4  is aryl of 6 to 12 carbon atoms optionally substituted with one or more substituents selected from alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, hydroxy, alkoxy of 1 to 10 carbon atoms, perhaloalkyl of 1 to 10 carbon atoms, perhaloalkoxy of 1 to 10 carbon atoms, —CN, —NO 2 , and halogen, heteroaryl having 5 or 6 ring atoms containing 1 to 3 heteroatoms which may be the same or different selected from nitrogen, oxygen and sulfur, optionally substituted with 1 to 3 stibstituents which may be the same or different selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO 2 , and halogen, bicyclic heteroaryl having 8 to 20 ring atoms containing 1 to 3 heteroatoms which may be the same or different selected from nitrogen, oxygen and sulfur optionally substituted with 1 to 3 substituents which may be the same or different, selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO 2 , and halogen;  
 with the proviso that X is not the radical  
                     
 when R 5  is H, halogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms and hydroxyl; n is 0;R 2  is H; Y is the radical  
                     
 and R 4  is phenyl substituted with three substituents which are the same or different selected from is , halogen, alkyl of 1 to 6 carbon atoms and alkoxy of 1 to 6 carbon atoms; or a pharmaceutically acceptable salt thereof together with one or more pharmaceutically acceptable carriers.  
 
     
     
         15 . A method of treating serotonergic neuron-related diseases in warm-blooded animals in need thereof, which comprises administering to said warm-blooded animals preferably mammals, most preferably humans an effective amount of a compound of Formula (I)  
       
         
           
           
               
               
           
         
       
       wherein: 
 n is an integer of 1 to 5;  
 X is a moiety selected from the group consisting of:  
                     
 Y is a moiety selected from the group consisting of:  
                     
 R 1  is aryl of 6 to 12 carbon atoms optionally substituted with one, or more substituents selected from alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, hydroxy, alkoxy of 1 to 10 carbon atoms, perhaloalkyl of 1 to 10 carbon atoms, perhaloalkoxy of 1 to 10 carbon atoms, —CN, —NO 2 , and halogen, heteroalyl having 5 or 6 ring atoms containing 1 to 3 heteroatoms which may be the same or different, selected from nitrogen, oxygen and sulfur, optionally substituted with 1 to 3 substituents which may be the same or different selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO 2 , and halogen; bicyclic heteroaryl having 8 to 20 ring atoms containing 1 to 3 heteroatoms which may be the same or different selected from nitrogen, oxygen and sulfur optionally substituted with 1 to 3 substituents which may be the same or different, selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO 2 , and halogen;  
 R 2  is independently H, alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, alkoxy of 1 to 10 carbon atoms, hydroxy, —(CH 2 ) z -O-alkyl of 1 to 6 carbon atoms , —(CH 2 ) z -S-alkyl of 1 to 6 carbon atoms, —(CH 2 ) z OH, perhaloalklyl of 1 to 10 carbon atoms, perhaloalkoxy of 1 to 10 carbon atoms, —CN, —NO 2 , and halogen; aryl of 6 to 12 carbon atoms optionally substituted with one or more substituents selected from alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, hydroxy, alkoxy of 1 to 10 carbon atoms, perhaloalkyl of 1 to 10 carbon atoms, perhaloalkoxy of 1 to 10 carbon atoms, —CN, —NO 2 , and halogen; heteroaryl is a 5- or 6-numbered monocyclic heteroaromatic ring which contains 1 to3 heteroatoms which may be the same or different, selected from nitrogen, oxygen and sulfur, optionally substituted with 1 to 3 substituents which may be the same or different selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO 2 , and halogen; bicyclic heteroaryl is a bicyclic saturated, unsaturated or aromatic ring system having 8 to 20 ring atoms containing 1 to 3 heteroatoms which may be the same or different selected from nitrogen, oxygen and sulfur optionally substituted with 1 to 3 substituents which may be the same or different, selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO 2 , and halogen;  
 z is an integer of 1 to 3;  
 R 3  is independently cycloalkyl or cycloalkenyl of 3 to 10 carbon atoms;  
 R 4  is aryl of 6 to 12 carbon atoms optionally substituted with one or more substituents selected from alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 10 carbon atoms, alkenyl of 2 to 10 carbon atoms, alkynyl of 2 to 10 carbon atoms, hydroxy, alkoxy of 1 to 10 carbon atoms, perhaloalkyl of 1 to 10 carbon atoms, perhaloalkoxy of 1 to 10 carbon atoms, —CN, —NO 2 , and halogen; heteroaryl having 5 or 6 ring atoms containing 1 to 3 heteroatoms which may be the same or different, selected from nitrogen, oxygen and sulfur, optionally substituted with 1 to 3 substituents which may be the same or different selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO 2 , and halogen, bicyclic heteroaryl having, 8 to 20 ring atoms containing 1 to 3 heteroatoms which may be the same or different selected from nitrogen, oxygen and sulfur optionally substituted with 1 to 3 substituents which nay be the same or different, selected from alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, —CN, —NO 2 , and halogen;  
 with the proviso that X is not the radical  
                     
 when R 5  is X, halogen, alkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms and hydroxyl; n 1is 0; R, is H; Y is the radical  
                     
 and R 4  is phenyl substituted with three substituents which are the same or different selected from A, halogen, alkyl of 1 to 6 carbon atoms and alkoxy of 1 to 6 carbon atoms; or a pharmaceutically acceptable salt thererof.  
 
     
     
         16 . The method of  claim 15  wherein the serotonergic neuron-related disease in warm-blooded animals is selected from the group consisting of anxiety, depression, eating disorders, high blood pressure, emesis, schizophrenia, the cognitive deficits resulting from neurodegenerative diseases of Alzheimer's Disease and prostate cancer.  
     
     
         17 . The method of  claim 16  wherein the serotonergic neuron-related disease in warm-blooded animals is depression.  
     
     
         18 . The method of  claim 16  wherein the serotonergic neuron-related disease in warm-blooded animals is anxiety.  
     
     
         19 . The method of  claim 16  wherein the serotonergic neuron-related disease in warm-blooded animals is the neurodegenerative diseases of Alzheimer's Disease.