Cyclic carboxamide derivatives and their use as analgesics

Abstract

A compound of formula (I): ##STR1## or a salt or solvate thereof in which R. CO is an acyl group containing a substituted or unsubstituted carbocyclic or heterocyclic aromatic ring, R 1 and R 2 are independently C 1-6 alkyl or together form a C 3-6 polymethylene or alkylene group, and p is 1, 2, 3 or 4, is useful for treating pain.

We claim: 
     
       1. A compound of formula I: ##STR26## or a solvate or pharmaceutically acceptable salt thereof in which R has the formula (II):   --(CHR.sub.4).sub.n --X--Ar--(R.sub.3).sub.m               (II)     in which   n is 0, 1 or 2,   m is 0, 1 or 2,   X is a direct bond, or O, S or NR 5 , in which R 5  is hydrogen or C 1-6  alkyl,   Ar is phenyl or thienyl,   R 3  is halogen, C 1-6  alkoxy, cyano, --COOR 4 , C 1-6  alkyl, or amino or, when m is 2, two R 3  's form a C 3-6  polymethylene group, and R 4  is hydrogen or C 1-6  alkyl,   R 1  and R 2  are .[.independently C 1-6  alkyl or together form a C 3-6  polymethylene or C 3-6  alkenylene group.]. .Iadd.each methyl or together with the nitrogen atom to which they are attached form 1-pyrrolidinyl.Iaddend.; and   p is 1, 2, 3 or 4.   
     
     
       2. A compound according to claim 1, in which each of R 1  and R 2  is methyl.[., ethyl, propyl, butyl, pentyl or hexyl.].. 
     
     
       3. A compound according to claim 1, in which R 1  and R 2  together .Iadd.with the nitrogen atom to which they are attached .Iaddend.form .[.a propylene, butylene, pentylene or hexylene group.]. .Iadd.1-pyrrolidinyl.Iaddend.. .[.4. The compound according to claim 1, in which R 1  and R 2  together form a --CH 2  --CH═CH--CH 2   
     
     
        -- group..]. 5. A compound according to claim 1, in which Ar is phenyl. 
     
     
           A compound according to claim 1 in which p is 2. 7. A compound selected from: 1-(3,4-dichlorophenyl)acetyl-2-(1-pyrrolidinyl)methyl piperidine hydrochloride,   1-(3,4-dichlorophenyl)acetyl-2- dimethylaminomethyl piperidine hydrochloride,   (2R)-1-(3,4-dichlorophenylacetyl)-2-(1-pyrrolidinylmethyl)piperidine hydrochloride hydrate,   -(2S)-1-(3,4-dichlorophenylacetyl-2-(1-pyrrolidinylmethyl)piperidine hydrochloride hydrate,   -(2S)-1-(3,4-dichlorophenylacetyl)-2-dimethylaminomethylpiperidine sesquihydrate,   -1-(3,4-dichlorophenylacetyl-2-(1-pyrrolidinylmethyl)pyrrolidine hydrochloride,   -1-(3,4-dichlorophenylacetyl-2-dimethylaminomethyl-pyrrolidine hydrochloride,   -1-(3,4-dichlorophenylacetyl-2-(1-pyrrolidinylmethyl)hexahydroazepine hydrochloride,   -1-(3,4-dichlorophenylacetyl-2-dimethylaminomethylhexahydroazepine hydrochloride hydrate,   -1-phenylacetyl-2-(1-pyrrolidinylmethyl)piperidine hydrochloride,   1-(3,4-dimethylphenylacetyl)-2-(1-pyrrolidinylmethyl)piperidine hydrochloride,   1-(5-indaneacetyl)-2-(1-pyrrolidinylmethyl)piperidine hydrochloride,   1-(6-tetralylacetyl)-2-(1-pyrrolidinylmethyl) piperidine hydrochloride,   1-(4-chlorophenylacetyl)-2-(1-pyrrolidinylmethyl) piperidine hydrochloride,   1-(3,4-dimethoxyphenylacetyl-2-(1-pyrrolidinylmethyl)piperidine hydrochloride,   1-(2-phenylbutyroil)-2-(1-pyrrolidinylmethyl) piperidine hydrochloride,   1-(4-chlorophenoxyacetyl)-2-(1-pyrrolidinylmethyl) piperidine   
     
     
        hydrochloride. 8. A pharmaceutical composition for treating pain in mammals, comprising an effective amount of a compound according to claim 
     
     
        1, and a pharmaceutically acceptable carrier. 9. A composition according 
     
     
        to claim 8 in unit dosage form. 10. A method of treating pain in mammals which comprises administering an effective non-toxic amount of a compound according to claim 1 to a sufferer.