[Synthesis and dual antagonistic activity against thromboxane A2 and leukotriene D4 of benzenesulfonamide derivatives].
In order to find dual antagonists against both thromboxane A2 (TXA2) and leukotriene D4 (LTD4) receptors for a new antiasthmatic agent, various benzenesulfonamide derivatives were synthesized and evaluated for those pharmacological effects. TXA2 and LTD4 antagonistic activities in vitro were evaluated by the inhibitory effects on LTD4-induced and U-46619-induced contraction of guinea-pig trachea. Furthermore, TXA2 and LTD4 antagonistic activities in vivo were evaluated by the inhibitory effects on LTD4-induced and U-46619-induced bronchoconstriction of guinea-pig after oral administration of test compounds. It was found that 4-[5-[1-(4-chlorobenzenesulfonamido)-5-methylhexyl]-2-thi eny l]butyric acid and 4-[5-[1-(4-fluorobenzenesulfonamido)-5-methyl-hexyl]-2-thienyl]but yric acid possess good anti-LTD4 and anti-TXA2 activities by oral administration.
Sakurai
S
S
Research and Development Division, Hokuriku Seiyaku, Co., Ltd., Japan.
Ogawa
N
N
Onogi
Y
Y
Ohashi
T
T
Kado
N
N
Yasuda
S
S
Kato
H
H
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D016084:Bronchoconstriction / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D017998:Leukotriene D4 / Q000037:antagonists & inhibitors*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors*; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors; D000096926:Benzenesulfonamides
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D018927:Anti-Asthmatic Agents; D017998:Leukotriene D4; D011450:Prostaglandin Endoperoxides, Synthetic; D013449:Sulfonamides; D013928:Thromboxane A2; D014662:Vasoconstrictor Agents; D000096926:Benzenesulfonamides