Synthetic studies on condensed-azole derivatives. III. Synthesis and anti-asthmatic activities of C-substituted alkyl side chain derivatives of omega-sulfamoylalkylthioimidazo[1,2-b]pyridazines and related compounds.
A series of novel alkylthioimidazo[1,2-b]pyridazines was synthesized and evaluated for ability to inhibit platelet activating factor (PAF)-induced bronchoconstriction in guinea pigs. Among them, 3-(imidazo[1,2-b]pyridazin-6-yl)thio-2,2-dimethylpropanesulfona mide (15) showed the most potent inhibitory effect. The structure-activity relationships in this series of compounds, in particular, the effects of conversion of the imidazopyridazine ring into other heterocyclic rings, introduction of a substituent group at the 2 or 3 position of the imidazopyridazine ring and introduction of a substituent group into the alkyl side chain, are also discussed.
Kuwahara
M
M
Pharmaceutical Research Division, Takeda Chemical Industries, Ltd., Osaka, Japan.
Kawano
Y
Y
Shimazu
H
H
Yamamoto
H
H
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; D013329:Structure-Activity Relationship; 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; D013806:Theophylline; D013930:Thromboxane-A Synthase