Synthesis and analgesic activities of some (4-substituted phenyl-1-piperazinyl)alkyl 2-aminobenzoates and 2-aminonicotinates.

A series of (4-substituted phenyl-1-piperazinyl)alkyl 2-aminobenzoates and 2-aminonicotinates has been prepared and screened for analgesic and antiinflammatory properties in mice and rats. The tabulated results reveal several 2-(4-substituted phenyl-1-piperazinyl)ethyl 2-(7- or 8-substituted 4-quinolinylamino)benzoates to be six to nine times more potent analgesics than the reference compounds (glafenine and aminopyrine) and to possess minor antinflammatory activity. Compound 45, 2-[4-[3-(trifluoromethyl)phenyl]-1-piperazinyl]ethyl 2-[[7-(trifluoromethyl)-4-quinolinyl]amino]benzoate (antrafenine), showed marked analgesic activity, long duration of action, and excellent tolerance in pharmacological and toxicological studies, as well as in clinical trials.