title: [Studies on the synthesis of condensed pyridazine derivatives. III. Synthesis and benzodiazepine receptor binding studies of condensed triazolopyridazine derivatives].
abstract: 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 [3H] 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.
authors.affiliation: Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nakao
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
authors.forename: Y
authors.initials: Y
authors.lastname: Morimoto
authors.forename: S
authors.initials: S
authors.lastname: Takehara
authors.forename: K
authors.initials: K
authors.lastname: Demizu
authors.forename: T
authors.initials: T
authors.lastname: Tahara
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000378:metabolism / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D011724:Pyridazines / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D014151:Anti-Anxiety Agents; D011724:Pyridazines; D011963:Receptors, GABA-A; C021604:CL 218872