Synthesis and Anticonvulsant Activity of 1-(2-(8-(benzyloxy)quinolin-2-yl)-1- butyrylcyclopropyl)-3-Substituted Urea Derivatives

摘要

In the present study on the development of new anticonvulsants, 16 new1-(2-(8-(benzyloxy)quinolin- 2-yl)-1-butyrylcyclopropyl)-3-substituted urea derivatives were synthesized and tested for anticonvulsant activity using the maximal electroshock seizure, subcutaneous pentylenetetrazole screens, which are the most widely employed seizure models for early identification of candidate anticonvulsants. Their neurotoxicity was determined by applying the rotorod test. Three compounds 7a, 7e, and 7m showed promising anticonvulsant activities in both models employed for anticonvulsant evaluation. The most active compound 7e showed the maximal electroshock seizure-induced seizures with ED_(50) value of 14.3 mg? kg and TD_(50) value of 434 mg/kg after intraperitoneal injection to mice, which provided compound 7e with a protective index (TD_(50)/ED_(50)) of 30.3 in the maximal electroshock seizure test.