SYNTHESIS AND EVALUATION OF NOVEL 2-ARYL-2,5,6,7-TETRAHYDRO-3H-THIENO[2',3' 6,7]CYCLOHEPTA[1-2-C]PYRIDAZINE-3-ONES AND 2-ARYL-5,6-DIHYDROTHIENO [2,3-H]CINNOLIN-3(2H)-ONES AS ANXIOLYTICS/

A series of thieno[2',3':6,7]cyclohepta[1,2-c]pyridazin-3-ones and 2-a ryl-5,6-dihydrothieno[2,3-h]cinnolin-3(2H)-ones were synthesized and e valuated for their affinity to benzodiazepine receptors (BZRs) in the excised brain of rats and also for their intrinsic efficacy in augment ation of the gamma-aminobutyric acid-induced chloride currents in the dissociated sensory neurons of frogs. The synthesized compounds showed a high affinity to BZRs. In these compounds, the substituents at the 2-position and at either the 8- or the 9-position and the ring size of the condensed ring affected the biological activity of the compounds. Thus, an introduction of 4-methyl- or 4-chloro-substitute phenyl ring into the 2-position, an introduction of methyl or ethyl into either t he 8- or the 9-position, and an expansion of the 6-membered condensed ring to a 7-membered ring brought about a continuous shift of compound s from inverse to full agonists. Among the synthesized compounds, 8-(1 phenyl)-5,6-dihydrothieno[2,3-h]cinnolin-3(2H)-one which can be class ified as a BZR partial agonist, was found to exhibit an anxio-selectiv e feature.