Piperazine compounds

Abstract

A compound selected from those of formula (I): wherein: R 1 , R 2 , R 3 and R 4 , which may be the same or different, each represent an atom or group selected from hydrogen, halogen, alkyl, alkoxy, phenyl and cyano, X represents a bond, an oxygen atom or a group selected from —(CH 2 ) m —, —OCH 2 — and —NR 5 —, wherein m represents 1 or 2, and R 5 is as defined in the description, Y represents an oxygen atom or a group selected from NR 7 and CHR 8 , wherein R 7 and R 8 are as defined in the description, Z represents a nitrogen atom or a CH group, n represents 1 or 2, Ak represents an alkylene chain, Ar represents an aryl or heteroaryl group, its optical isomers, and addition salts thereof with a pharmaceutically acceptable acid. Medical products containing the same which are useful in the treatment of conditions requiring a serotonin reuptake inhibitor and/or NK 1 antagonist.

1 . A compound selected from those of formula (I): 
       
         
           
           
               
               
           
         
         wherein:
 R 1 , R 2 , R 3  and R 4 , which may be the same or different, each represent an atom or group selected from hydrogen, halogen, linear or branched C 1 -C 6 alkyl, linear or branched C 1 -C 6 alkoxy, phenyl and cyano, 
 X represents a bond, an oxygen atom or a group selected from —(CH 2 ) m —, —OCH 2 — and —NR 5 —,
 m represents 1 or 2, 
 R 5  represents a hydrogen atom or a group selected from linear or branched C 1 -C 6 alkyl, COR 6  and CO 2 R 6 , 
 R 6  represents a linear or branched C 1 -C 6 alkyl group, 
 
 Y represents an oxygen atom or a group selected from NR 7  and CHR 8 ,
 R 7  represents a hydrogen atom or a group selected from COR 9  and linear or branched C 1 -C 6 alkyl, the alkyl group being optionally substituted by a 5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl or 2,3-dihydro-1,4-benzodioxin-2-yl group, 
 R 9  represents a group selected from linear or branched C 1 -C 6 alkyl, aryl and heteroaryl, 
 R 8  represents a hydrogen atom or an amino group optionally substituted by one or two linear or branched C 1 -C 6 alkyl groups, 
 
 Z represents a nitrogen atom or a CH group, 
 n represents 1 or 2, 
 Ak represents a linear or branched C 1 -C 6 alkylene chain, 
 Ar represents an aryl or heteroaryl group, 
 
         its optical isomers, and addition salts thereof with a pharmaceutically acceptable acid, 
         it being understood that 
         if Y represents NR 7 , then Z represents CH; 
         an aryl group means phenyl, biphenylyl or naphthyl, each of the groups optionally being substituted by one or more identical or different groups selected from halogen, linear or branched C 1 -C 6 alkyl, linear or branched C 1 -C 6 alkoxy, hydroxy, cyano, linear or branched C 1 -C 6 trihaloalkyl and linear or branched C 1 -C 6 trihaloalkoxy; 
         and a heteroaryl group means an aromatic mono- or bi-cyclic 5- to 12-membered group containing one, two or three hetero atoms selected from oxygen, nitrogen and sulphur, which may optionally be substituted by one or more identical or different groups selected from halogen, linear or branched C 1 -C 6 alkyl, linear or branched C 1 -C 6 alkoxy, hydroxy, cyano and linear or branched C 1 -C 6 trihaloalkyl. 
       
     
     
         2 . The compound of  claim 1 , wherein Y represents NH. 
     
     
         3 . The compound of  claim 1 , wherein Z represents a nitrogen atom. 
     
     
         4 . The compound of  claim 1 , wherein n represents 1. 
     
     
         5 . The compound of  claim 1 , wherein Ar represents an aryl group. 
     
     
         6 . The compound of  claim 1 , wherein X represents a bond, an oxygen atom or a group selected from —OCH 2 — and —(CH 2 ) m — wherein m represents 1 or 2. 
     
     
         7 . A pharmaceutical composition comprising as active ingredient a compound of  claim 1 , in combination with one or more pharmaceutically acceptable, inert, non-toxic carriers. 
     
     
         8 . A method for treating a living animal body, including a human, afflicted with a condition requiring a serotonin reuptake inhibitor comprising the step of administering to the living animal body, including a human, an amount of a compound of  claim 1  which is effective for alleviation of the condition. 
     
     
         9 . A method for treating a living animal body, including a human, afflicted with a condition requiring a serotonin reuptake inhibitor and an NK 1  antagonist comprising the step of administering to the living animal body, including a human, an amount of a compound of  claim 1  which is effective for alleviation of the condition. 
     
     
         10 . A method for treating a living animal body, including a human, afflicted with a condition selected from depressive states, anxiety states, impulsive disorders, aggressive behaviours, drug abuse, obesity and appetite disorders, pain and inflammation, dementias, psychotic states, disturbances of chronobiological rhythms, nausea or gastrointestinal disorders comprising the step of administering to the living animal body, including a human, an amount of a compound of  claim 1  which is effective for alleviation of the condition.