Synthetic studies on condensed-azole derivatives. I. Synthesis and anti-asthmatic activities of omega-substituted alkylthioimidazo[1,2-b]pyridazines.
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.
Kuwahara
M
M
Pharmaceutical Research Division, Takeda Chemical Industries, Ltd., Osaka, Japan.
Kawano
Y
Y
Kawai
T
T
Ashida
Y
Y
Miyake
A
A
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001993:Bronchodilator Agents / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*; D014132:Trachea / Q000187:drug effects
D018927:Anti-Asthmatic Agents; D001993:Bronchodilator Agents; D004791:Enzyme Inhibitors; D010972:Platelet Activating Factor; D011724:Pyridazines; D013806:Theophylline; D013930:Thromboxane-A Synthase