Derivatives of n-phenyl(piperidine-2-yl) methyl benzamide preparation method thereof and applications of same in therapeutics

Abstract

Compounds of formula (I) as defined herein: are useful for treating behavioral disorders associated with dementia, psychoses, in particular schizophrenia (deficient form and productive form) and acute or chronic extrapyramidal symptoms induced by neuroleptics; for the treatment of various forms of anxiety, panic attacks, phobias, and compulsive obsessive disorders; for treating various forms of depression, including psychotic depression; for treating disorders caused by alcohol abuse or weaning from alcohol, sexual behavior disorders, eating disorders and for treating migraine. Moreover, the compounds of the invention may be used for treating painful muscle contracture in rheumatology and in acute spinal pathology; for treating spastic contractures of medullary or cerebral origin; for the symptomatic treatment of acute and subacute pain of light to moderate intensity; for treating intense and/or chronic pain, neurogenic pain and intractable pain; for treating Parkinson's disease and Parkinson-like symptoms of neurodegenerative origin or induced by neuroleptics; for treating partial primary and secondary generalized epilepsy of simple or complex symptomology, mixed forms and other epileptic syndromes in addition to another antiepileptic treatment, or in monotherapy, for the treatment of sleep apnea, and for neuroprotection.

1 . A compound of formula (I) 
     
       
         
         
             
             
         
       
     
     in which
 R 1  represents either a hydrogen atom or a linear or branched (C 1 -C 7 )alkyl group optionally substituted with one or more fluorine atoms, or a (C 3 -C 7 )cycloalkyl group, or a (C 3 -C 7 )cycloalkyl (C 1 -C 3 )alkyl group, or a phenyl(C 1 -C 3 )alkyl group optionally substituted with one or two methoxy groups, or a (C 2 -C 4 )alkenyl group, or a (C 2 -C 4 )alkynyl group; 
 X represents a hydrogen atom or one or more substituents chosen from halogen atoms and trifluoromethyl and linear or branched (C 1 -C 4 )alkyl and (C 1 -C 4 )alkoxy groups; 
 R 2  represents a group chosen from naphthyl, pyridinyl, pyrimidinyl, pyrazinyl, pyridyl, triazinyl, indanyl, indenyl, quinolyl, isoquinolyl, quinazolyl, quinoxalyl, phthalazinyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, thiadiazolyl, oxadiazolyl, triazolyl, benzofuryl, benzimidazolyl, benzothiazolyl, indolyl, isoindolyl, indazolyl, benzoxazolyl, benzisoxazolyl, benzotriazolyl, benzisothiazolyl, dihydroindolyl, pyrrolopyridyl, furopyridyl, thienopyridyl, imidazopyridyl, oxazolopyridyl, thiazolopyridyl, pyrazolopyridyl, isoxazolopyridyl, isothiazolopyridyl, tetrahydroquinolyl and tetrahydroisoquinolyl groups, and optionally substituted with one or more substituents chosen from halogen atoms and (C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, thio(C 1 -C 4 )alkyl or phenyl groups optionally substituted with one or more substituents chosen from halogen atoms and trifluoromethyl, (C 1 -C 4 )alkyl and (C 1 -C 4 )alkoxy groups; 
 
     or an acid-addition salt thereof. 
   
   
       2 . A pharmaceutical composition which comprises a compound according to  claim 1 , or a pharmaceutically acceptable salt thereof, combined with an excipient. 
   
   
       3 . A method for treating a behavioral disorder selected from the group consisting of dementia, psychoses, various forms of anxiety, panic attacks, phobias, compulsive obsessive disorders, various forms of depression, disorders caused by alcohol abuse or weaning from alcohol, sexual behavior disorders, eating disorders and migraine, which comprises administering to a patient with said disorder an effective amount of a compound according to  claim 1 , or a pharmaceutically acceptable salt thereof. 
   
   
       4 . A method for treating a condition selected from the group consisting of contracture, pain, Parkinson's disease and Parkinson-like symptoms, epilepsy, mixed forms and other epileptic syndromes in addition to another antiepileptic treatment, or in monotherapy, sleep apnea, and neuroprotection migraine, which comprises administering to a patient in need thereof an effective amount of a compound according to  claim 1 , or a pharmaceutically acceptable salt thereof. 
   
   
       5 . The compound according to  claim 1 , which is threo-4-[2-chloro-3-(trifluoromethyl)phenyl]-N-[(1-methyl-2-piperidyl)(phenyl)methyl]-1H-imidazole-2-carboxamide.