STUDIES ON THE SYNTHESIS OF CONDENSED PYRIDAZINE DERIVATIVES .3. SYNTHESIS AND BENZODIAZEPINE RECEPTOR-BINDING STUDIES OF CONDENSED TRIAZOLOPYRIDAZINE DERIVATIVES

A series of 6H-(1)benzothiopyrano[3,4-e][1,2,4]triazolo[4,3-b]pyridazines and 6,7-dihydro-(1)benzothiepino[4,5-e][1,2,4]triazolo[4,3-b]pyridazines were prepared and tested for their ability to displace [H-3]diazepam from rat brain membranes. An approximately planar shape of these molecules was essential for high affinity to the benzodiazepine receptor. Among them, 11-aryl compounds in the latter series were found to have high affinity to the benzodiazepine receptor. 11-Phenyl- and 11-thienyl-6,7-dihydro-(1)benzothiepino[4,5-e][1,2,4]triazolo[4,3-b]pyridazine(3b-5 and 3b-11 respectively) showed the potent affinity comparable to that of diazepam. The structure-activity relationships are also discussed.