Synthesis and structure-activity analysis of 2-(4-chlorophenyl)-5,6-dihydrothienothiepinopyridazin-3(2H)-ones as ligands for benzodiazepine receptors

Article abstract of DOI:10.1016/0223-5234(96)88305-X

A series of 2-(4-chlorophenyl)-5,6-dihydrothieno<2'3':2,3>thiepino<4,5-c>pyridazin-3(2H)-ones were synthesized and evaluated in vitro for their affinity toward benzodiazepine receptors (BZRs) in rats and for their intrinsic efficacy in the augmentation of the γ-aminobutyric acid (GABA)-induced chloride currents in the dissociated frog sensory neurons.Compounds in wich the 9-position of the condensed-ring system was substituted with alkyl group or bromine had a high affinity toward BZRs.The substituents at the same position also influenced significantly the GABA-induced chloride currents.As the result, 9-alkyl and 9-bromo substutuents would interact with the lipophilic area of BZRs.A series of 2-(4-chlorophenyl)-5,6-dihydrothieno<2',3':2,3>thiepino<4,5-c>pyridazin-3(2H)-ones exhibited partial and full agonistic activities toward BZRs. benzodiazepine receptor / γ-aminobutyric acid / partial agonist / full agonist / structure activity relationship