SYNTHESIS AND STRUCTURE-ACTIVITY ANALYSIS OF PHENYL)5,6-DIHYDROTHIENO[2',3'-2,3]THIEPINO[4,5-C] PYRIDAZIN-3(2H)-ONES AS LIGANDS FOR BENZODIAZEPINE RECEPTORS

A series of ieno[2',3':2,3]thiepino[4,5-c]pyridazin-3(2H)-ones were sy nthesized and evaluated in vitro for their affinity tow-ard benzodiaze pine receptors (BZRs) in rats and for their intrinsic efficacy in the augmentation of the gamma-aminobutyric acid (GABA)-induced chloride cu rrents in the dissociated frog sensory neurons. Compounds in which the 9-position of the condensed-ring system was substituted with alkyl gr oup or bromine had a high affinity toward BZRs. The substituents at th e same position also influenced significantly the GABA-induced chlorid e currents. As the result, 9-alkyl and 9-bromo substituents would inte ract with the lipophilic area of BZRs. A series of ieno[2',3':2,3]thie pino[4,5-c]pyridazin-3(2H)-ones exhibited partial and full agonistic a ctivities toward BZRs.