Studies on Cerebral Protective Agents. X. Synthesis and Evaluation of Anticonvulsant Activities for Novel 4, 5, 6, 7-Tetrahydrothieno[3, 2-c]pyridines and Related Compounds

Abstract

Novel 4, 5, 6, 7-tetrahydrothieno[3, 2-c]pyridines, 1-thienyl-1, 2, 3, 4-tetrahydroisoquinolines and related compounds, in which the benzene rings of (+)-1 (FR115427) were replaced with heteroaromatic rings such as thiophene, furan, benzothiophene and indole, were synthesized and evaluated for anticonvulsant activity against i.c.v. N-methyl-D-Aspartate (NMDA)-induced seizures in mice, Among these compounds, (+)-4-methyl-4-phenyl-4, 5, 6, 7-tetrahydrothieno[3, 2-c]pyridine hydrochloride ((+)-2a), (+)-4-methyl-4-(2-thienyl)-4, 5, 6, 7-tetrahydrothieno[3, 2-c]pyridine hydrochloride ((+)-2g), and (-)-1-methyl-1-(2-thienyl)-1, 2, 3, 4-tetrahydroisoquinoline hydrochloride ((-)-3a) showed significant anticonvulsant activity. The structure-activity relationships with regard to the anticonvulsant activity of this series of compounds are discussed.