Suzuki T, Matsuhisa A, Miyata K, Yanagisawa I, Ohta M
Neuroscience/Gastrointestinal Research Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
Chem Pharm Bull (Tokyo). 1997 Jan;45(1):101-6. doi: 10.1248/cpb.45.101.
Novel 9-methyl-4,9-dihydrothiopyrano[2,3-b]indol-4-one derivatives 2b-e, 3-methylene-9-methyl-2,3,4,9-tetrahydrothiopyrano[2,3-b]indol-4-on e derivatives 3b-e and 9-methyl-2,3,4,9-tetrahydrothiopyrano[2,3-b]indol-4-one derivatives 4a-e were prepared. The 5-hydroxytryptamine (5-HT3) receptor-antagonistic activities of these compounds were evaluated by using the von Bezold-Jarisch reflex test (B. J. reflex, rats) and the contractile response to 5-HT in the isolated distal colon (guinea pig). The 5-ethyl-4-imidazolyl derivative 4d was found to be 79 times more potent than ondansetron 1 in the B. J. reflex test (ID50 = 0.048 microgram/kg, i.v.), and the 5-methyl-4-imidazolyl derivative 4c was found to be 126 times more potent than 1 in the colonic contraction (IC50 = 0.0062 microM) assay.
制备了新型9-甲基-4,9-二氢噻喃并[2,3 - b]吲哚-4-酮衍生物2b - e、3-亚甲基-9-甲基-2,3,4,9-四氢噻喃并[2,3 - b]吲哚-4-酮衍生物3b - e和9-甲基-2,3,4,9-四氢噻喃并[2,3 - b]吲哚-4-酮衍生物4a - e。通过使用冯贝佐尔德-雅里什反射试验（B.J.反射，大鼠）和分离的远端结肠（豚鼠）对5-羟色胺（5-HT3）的收缩反应来评估这些化合物的5-羟色胺（5-HT3）受体拮抗活性。发现5-乙基-4-咪唑基衍生物4d在B.J.反射试验中比昂丹司琼1强79倍（ID50 = 0.048微克/千克，静脉注射），并且5-甲基-4-咪唑基衍生物4c在结肠收缩（IC50 = 0.0062微摩尔）试验中比1强126倍。
