Substituted piperidines therapeutic process and compositions

Abstract

The compounds are of the heterocyclic class of 2-phenethylpiperidines having an amido substituent in the ortho position of the phenethyl moiety. Substituents in the ortho position include formamido, benzamido, cinnamamido, 2-thiophenecarboxamido, alkanesulfonamido and alkanoylamido. They are useful as antiarrhythmic and/or antiserotonin agents. The novel compounds are prepared by reaction of appropriately substituted o-aminophenethylpiperidines and the carbonyl or sulfonyl halides or anhydrides. Typical embodiments of this invention are 4-methoxy-2'-[2-(1-methyl-2-piperidyl)ethyl]benzanilide and 2'-[2-(1-methyl-2-piperidyl)ethyl]cinnamanilide.

What is claimed is:  .[.1. A process for eliciting an antiarrhythmic effect in a mammal in need of said effect which comprises systemic administration to said mammal of a non-toxic effective antiarrhythmic dose of from about 0.01 to 20 mg./kg. of body weight of said mammal of a compound from the group consisting of a substituted piperidine having Formula I ##STR38## wherein R 1  represents hydrogen 
     
        salt thereof..]. .[.2.  The process of claim 1 in which the compound is 4-methoxy-2'[2-(1-methyl-2-piperidyl)ethyl]benzanilide..]. .[.3. The process of claim 1 in which the compound is 4-methoxy-2'-[2-(1-methyl-2-piperidyl)ethyl]benzanilide hydrochloride..]. .[.4. The process of claim 1 in which the compound is 4-chloro-2'-[2-(1-methyl-2-piperidyl)ethyl]benzanilide..]. .[.5. The process of claim 1 in which the compound is 2'-[2(1-methyl-2-piperidyl)ethyl]benzanilide..]. .[.6. A process for eliciting an antiarrhythmic effect in a mammal in need of said effect which comprises systemic administration to said mammal of a non-toxic effective dose of from about 0.01 to 20 mg./kg. of body weight of said mammal of a compound selected from the group consisting of a substituted piperidine having Formula XII ##STR40## wherein R 8  represents lower alkyl of 1 to 4 carbon atoms inclusive; R 9  is selected from the group consisting of cinnamoyl or ##STR41## wherein Rd 10  is methoxy;   A is a divalent radical selected from the group consisting of --CH 2  --, ##STR42## and --(CH 2 ) 3  --; and a pharmaceutically acceptable salt   
     
     
        thereof..]. .[.7.  The process of claim 6 in which the compound is 2'-[3-(1-methyl-2-piperidyl)propyl]p-anisanilide..]. .[.8. The process of claim 6 in which the compound is 2'-[(1-methyl-2-piperidyl)methyl]-p-anisanilide..]. .[.9. A process for eliciting an antiserotonin effect in a mammal in need of said effect which comprises sytemic administration to said mammal of a non-toxic antiserotonin effective dose of from about 0.01 to 20 mg./kg. of body weight of said host of the compound 2'-[2-(1-methyl-2-piperidyl)ethyl]-cinnamanilide or a pharmaceutically acceptable acid addition salt thereof..]. .[.10. The process of claim 9 in which the compound is 2'-[2-(1-methyl-2-piperidyl)ethyl]cinnamanilide hydrochloride..]. .[.11. A pharmaceutical composition in dosage unit form suitable for systemic administration to a mammal comprising a pharmaceutical carrier containing from 1 to 500 milligrams of an active ingredient selected from the group consisting of a compound having Formula I ##STR43## wherein R 1  represents hydrogen; R 2  represents hydrogen or methylenedioxy attached in the benzenoid 4,5-position;   R 3  represents hydrogen or methyl;   R 4  represents hydrogen;   R 5  is selected from the group consisting of lower alkanoyl of from 1 to 4 carbon atoms inclusive, lower alkanesulfonyl of from 1 to 4 carbon atoms inclusive, cinnamoyl, ##STR44## wherein R 7  is selected from the group consisting of hydrogen, chlorine, dimethylamino, alkylthio of from 1 to 4 carbon atoms inclusive, alkyl of from 1 to 4 carbon atoms inclusive, methoxy, 3,4-dimethoxy, 3,5-dimethoxy, and 3,4,5-trimethoxy   
     
     
       and a pharmaceutically acceptable salt thereof..]. .[.12.  The compositions of claim 11 in which the active ingredient is 2'-[2-(1-methyl-2-piperidyl)ethyl]cinnamanilide..]. .[.13. The composition of claim 11 in which the active ingredient is 2'-[2-(1-methyl-2-piperidyl)ethyl]cinnamanilide hydrochloride..]. .[.14. The composition of claim 11 in which the active ingredient is 4-methoxy-2'-[2-(1-methyl-2-piperidyl)ethyl]benzanilide..]. .[.15. The composition of claim 11 in which the active ingredient is 4-methoxy-2'-[2-(1-methyl-2-piperidyl)ethyl]benzanilide hydrochloride..]. .[.16. The composition of claim 11 in which the active ingredient is 4-chloro-2'-[2-(1-methyl-2-piperidyl)ethyl]benzanilide..].  .[.17. The composition of claim 11 in which the active ingredient is 2'-[2-(1-methyl-2-piperidyl)ethyl]benzanilide..]. .[.18. A pharmaceutical composition in dosage unit form suitable for systemic administration to a mammal comprising a pharmaceutical carrier containing 1 to 500 milligrams of an active ingredient selected from the group consisting of a compound having Formula XII ##STR45## wherein R 8  represents lower alkyl of 1 to 4 carbon atoms inclusive; R 9  is selected from the group consisting of cinnamoyl or ##STR46## wherein R 10  is methoxy;   A is a divalent radical selected from the group consisting of --CH 2  --, ##STR47## and --(CH 2 ) 3  --; and a pharmaceutically acceptable salt   
     
     
        thereof..]. .[.19.  The composition of claim 18 in which the active ingredient is 2'-[3-(1-methyl-2-piperidyl)propyl]-p-anisanilide..]. .[.20. The composition of claim 18 in which the active ingredient is 
     
     
        2'-[(1-methyl-2-piperidyl)methyl]-p-anisanilide..]. .Iadd.21. 4-Hydroxy-2'-[2-(1-methyl-2-piperidyl)ethyl]benzanilide. .Iaddend.