[Studies on the synthesis of condensed pyridazine derivatives. III. 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 [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.
Nakao
T
T
Research Laboratories, Yoshitomi Pharmaceutical Industries, Ltd., Fukuoka, Japan.
Tanaka
H
H
Morimoto
Y
Y
Takehara
S
S
Demizu
K
K
Tahara
T
T
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
D014151:Anti-Anxiety Agents; D011724:Pyridazines; D011963:Receptors, GABA-A; C021604:CL 218872