[Synthesis and dual antagonistic activity against thromboxane A2 and leukotriene D4 of benzenesulfonamide derivatives]

Yakugaku Zasshi. 1997 May;117(5):298-318. doi: 10.1248/yakushi1947.117.5_298.
[Article in Japanese]

Abstract

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.

Publication types

  • English Abstract

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • Animals
  • Anti-Asthmatic Agents / chemical synthesis*
  • Anti-Asthmatic Agents / pharmacology*
  • Benzenesulfonamides
  • Bronchoconstriction / drug effects
  • Guinea Pigs
  • In Vitro Techniques
  • Leukotriene D4 / antagonists & inhibitors*
  • Prostaglandin Endoperoxides, Synthetic / antagonists & inhibitors
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / pharmacology*
  • Thromboxane A2 / analogs & derivatives
  • Thromboxane A2 / antagonists & inhibitors*
  • Vasoconstrictor Agents / antagonists & inhibitors

Substances

  • Anti-Asthmatic Agents
  • Prostaglandin Endoperoxides, Synthetic
  • Sulfonamides
  • Vasoconstrictor Agents
  • Thromboxane A2
  • Leukotriene D4
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid