Studies on the Synthesis of Condensed Pyridazine Derivatives. III. Synthesis and Benzodiazepine Receptor Binding Studies of Condensed Triazolopyridazine Derivatives

• Published in: YAKUGAKU ZASSHI Vol. 110; no. 12; pp. 922 - 931
• Main Authors: NAKAO, Tohru, TANAKA, Hiroshi, MORIMOTO, Yasuto, TAKEHARA, Shuzo, DEMIZU, Kenichi, TAHARA, Tetsuya
• Format: Journal Article
• Language: Japanese
• Published: Japan The Pharmaceutical Society of Japan 01.12.1990
• Subjects: 6, 7-dihydro- benzothiepino [4, 5-e] [1, 2, 4] triazolo [4, 3-b] pyridazine; Animals; Anti-Anxiety Agents - metabolism; Anti-Anxiety Agents - pharmacology; antianxiety; benzodiazepine receptor; binding assay; Brain - metabolism; non-benzodiazepine structure; Pyridazines - metabolism; Pyridazines - pharmacology; Rats; Receptors, GABA-A - metabolism; Structure-Activity Relationship
• ISSN: 0031-6903; 1347-5231
• DOI: 10.1248/yakushi1947.110.12_922

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.