2. Academic Validation
  3. Design, synthesis, and 5-lipoxygenase-inhibiting properties of 1-thio-substituted butadienes

Design, synthesis, and 5-lipoxygenase-inhibiting properties of 1-thio-substituted butadienes

  • J Med Chem. 1990 Apr;33(4):1163-70. doi: 10.1021/jm00166a013.
R Hanko 1,  M D Hammond,  R Fruchtmann,  J Pfitzner,  G A Place
Affiliations

Affiliation

  • 1 Molecular Therapeutics Inc., West Haven, Connecticut 06516.
PMID: 2319562 DOI: 10.1021/jm00166a013
Abstract

The synthesis of novel 1-thio-substituted butadienes, designed as mechanism-based 5-lipoxygenase inhibitors, is described. The structure of these compounds closely resembles a proposed high-energy intermediate during the lipoxygenation of arachidonic acid. They demonstrate 5-lipoxygenase inhibition in vitro and in vivo. The most potent compound is 15a with an IC50 of 1.8 microM in vitro. LTC4 release was inhibited by 80% after intraperitoneal administration of 15c at a dose of 2 mg/kg.

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