In order to find dual antagonists against both thromboxane A
2 (TXA
2) and leukotriene D
4 (LTD
4) receptors for a new antiasthmatic agent, various benzenesulfonamide derivatives were synthesized and evaluated for those pharmacological effects. TXA
2 and LTD
4 antagonistic activities in vitro were evaluated by the inhibitory effects on LTD
4-induced and U-46619-induced contraction of guinea-pig trachea. Furthermore, TXA
2 and LTD
4 antagonistic activities in vivo were evaluated by the inhibitory effects on LTD
4-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-thienyl] butyric acid (12i) and 4-[5-[1-(4-fluorobenzenesulfonamido)-5-methylhexyl]-2-thienyl] butyric acid (12j) possess good anti-LTD
4 and anti-TXA
2 activities by oral administration.
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