N-phenyl-N'-pyridinylureas as anticonvulsant agents.

A series of N-phenyl-N'-pyridinylureas was examined for anticonvulsant activity. Extensive structure/activity investigations revealed optimal activity in the N-(2,6-disubstituted-phenyl)-N'-(4-pyridinyl)urea series, with 37 exhibiting the best overall anticonvulsant profile. Compound 37 was effective against seizures induced by maximal electroshock but did not protect mice from clonic seizures produced by the convulsant pentylenetetrazol. The overall pharmacological profile suggests that 37 would be of therapeutic use in the treatment of generalized tonic-clonic and partial seizures. Compound 37 was selected for Phase 1 clinical trials.

Synthesis and anticonvulsant activity of racemic 2-amino-N-substituted succinimide derivatives.

Several derivatives of (R,S)-2-amino-N-substituted succinimides were synthetized and evaluated in mice against seizures produced by electroshock and pentylenetetrazol. The most active compound against both electroshock- and pentylenetetrazol-induced seizures was (R,S)-N-benzyl-2-(methanesulfamido)succinimide.