SYNTHESIS OF 2-PIPERIDINECARBOXYLIC ACID-DERIVATIVES AS POTENTIAL ANTICONVULSANTS

A variety of 2-piperidinecarboxamides were synthesized and evaluated f or anticonvulsant activity using the MES and sc PTZ tests in mice and rats. Neurotoxicity was determined by the rotorod test. Several N-(ben zyl)-2-piperidinecarboxamides exhibited potent MES activity in mice [2 -CF3 14, ED50 = 29 mg/kg; 3-F 16, ED50 = 31 mg/kg; and 3-CF3 17, ED50 = 24 mg/kg]. The most active compounds in the MES test in mice were th e 2,6-dimethylanilides [(R,S)-34, ED50 = 5.8 mg/kg; (R)-35, ED50 = 5.7 mg/kg; and (S)-36, ED50 = 14.8 mg/kg]. The enantiomer (S)-36 was abou t two-fold less potent in the MES test than (R)-35 and also was less n eurotoxic. Acylation of the piperidine ring nitrogen of 12 and 34 led to a decrease in the MES activity. In the N-(alpha-methylbenzyl)-2-pip eridine-carboxamides, the stereochemistry at either the 2-position of the piperidine ring or at the alpha-position of the N-(alpha-methylben zyl) group does not significantly affect MES activity. (C) Elsevier, P aris.