Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Synthetic Studies on Condensed-Azole Derivatives. IV. Synthesis and Anti-asthmatic Activities of ω-Sulfamoylalkyloxyimidazo[1, 2-b]pyridazines
Masaaki KUWAHARAYasuhiko KAWANOHiroshi SHIMAZUYasuko ASHIDAAkio MIYAKE
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1996 Volume 44 Issue 1 Pages 122-131

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Abstract

A series of novel (imidazo[1, 2-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 were found to have potent activity. Among them, 3-(imidazo[1, 2-b]pyridazin-6-yl)oxy-2, 2-dimethylpropanesulfonamide (6) showed excellent anti-asthmatic activity and the longest duration of action. The compounds bearing a methyl group at the 7 or 8 position of the imidazo[1, 2-b]pyridazine ring were found to have enhanced activity. Among them, 3-(7-methylimidazo[1, 2-b]pyridazin-6-yl)oxy-2, 2-dimethylpropanesulfonamide (25) showed the most potent inhibitory effect, and its anti-asthmatic effect in an experimental model of allergic asthma was superior to that of theophylline. The structure-activity relationships in this series of compounds are discussed.

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© The Pharmaceutical Society of Japan
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