Synthetic studies on condensed-azole derivatives. V. Synthesis and anti-asthmatic activities of omega-sulfamoylalkyloxy[1,2,4]triazolo[1,5-b]-pyridazines.
A series of novel ([1,2,4]triazolo[1,5-b]pyridazin-6-yl) oxyalkylsulfonamides was synthesized and evaluated for the ability to inhibit platelet activating factor (PAF)-induced bronchoconstriction in guinea pigs. The compounds bearing a gem-dialkyl or a cycloalkylidene group at the 2 position of the sulfamoylpropyloxy group in the side chain and a methyl group at the 7 position were found to have potent activity. Among them, 2,2-diethyl-3-(7-methyl[1,2,4]- triazolo[1,5-b]pyridazin-6-yl)oxypropanesulfonamide (13) showed excellent anti-asthmatic activity. Compounds 13 may be of significant value in the treatment of asthma and other respiratory diseases. The structure-activity relationships in this series of compounds are discussed.
Kuwahara
M
M
Pharmaceutical Research Division, Pharmaceutical Research Laboratories III, Takeda Chemical Industries, Ltd., Osaka, Japan.
Kawano
Y
Y
Kajino
M
M
Ashida
Y
Y
Miyake
A
A
D000818:Animals; D018927:Anti-Asthmatic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D018927:Anti-Asthmatic Agents; D011724:Pyridazines