Kuwahara M, Kawano Y, Kawai T, Ashida Y, Miyake A
Pharmaceutical Research Division, Takeda Chemical Industries, Ltd., Osaka, Japan.
Chem Pharm Bull (Tokyo). 1995 Sep;43(9):1505-10. doi: 10.1248/cpb.43.1505.
A series of novel omega-substituted alkylthioimidazo[1,2-b]pyridazines was designed and synthesized in an effort to find a novel anti-asthmatic agent. The anti-asthmatic activity of these compounds was evaluated on the basis of their ability to inhibit thromboxane A2 synthetase and platelet activating factor (PAF)-induced bronchoconstriction in guinea pigs. None of these compounds significantly inhibited thromboxane A2 synthetase, though, sulfonamide derivatives potently inhibited PAF-induced bronchoconstriction. Among them, 3-(imidazo[1,2-b]pyridazin-6-yl)thiopropanesulfonamide (5) showed the most potent inhibitory effect. The anti-asthmatic effects of compound 5 in experimental models were superior to those of theophylline.
为了找到一种新型抗哮喘药物，设计并合成了一系列新型的ω-取代烷基硫代咪唑并[1,2-b]哒嗪。根据这些化合物抑制血栓素A2合成酶的能力以及对豚鼠血小板活化因子（PAF）诱导的支气管收缩的抑制能力，对它们的抗哮喘活性进行了评估。然而，这些化合物均未显著抑制血栓素A2合成酶，不过，磺酰胺衍生物能有效抑制PAF诱导的支气管收缩。其中，3-(咪唑并[1,2-b]哒嗪-6-基)硫代丙烷磺酰胺（5）表现出最强的抑制作用。化合物5在实验模型中的抗哮喘作用优于茶碱。
