縮合Pyridazine誘導体の合成研究(第2報)2-Aryl-4,4a, 5,6-tetrahydropyridazino-[4,3-c]quinolin-3(2H)-one, 2-Aryl-4a, 5-dihydro-2H-(1)benzothiopyrano[4,3-c]-pyridazin-3(4H)-one誘導体, 及び関連化合物の合成と抗不安作用

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A series of 2-aryl-4,4a, 5,6-tetrahydropyridazino [4,3-c] quinolin-3 (2H)-ones, 2-aryl-4a, 5-dihydro-2H-(1) benzothiopyrano [4,3-c] pyridazin-3 (4H)-ones, and related compounds were synthesized and tested for their ability to displace [^3H] diazepam from rat brain membranes in vitro, and to prevent bicuculline-induced convulsions in mice in vivo. Among them, 2-(4-chlorophenyl)-4a, 5-dihydro-2H-(1) benzothiopyrano [4,3-c] pyridazin-3 (4H)-one (16b) showed remarkable activities both in vitro (K_i 48 nM) and in vivo (ED_<50> 12.4 mg/kg, p.o.). The trans sulfoxide (19a) of 16b exhibited anxioselective pharmacological activities. Compound 19a was equipotent with diazepam in the anticonflict assay (Vogel type, rat, MED 10 mg/kg, p. o.) while exhibiting reduced muscle relaxation (rotarod test) and narcotic potentiation. The structure-activity relationships are discussed.
公益社団法人日本薬学会の論文
1990-08-25