Design, Synthesis, and 5-Lipoxygenase-Inhibiting Properties of 1-Thio-Substiuted Butadienes

Article abstract of DOI:10.1021/jm00166a013

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 μM in vitro.LTC4 release was inhibited by 80percent after intraperitoneal administration of 15c at a dose of 2 mg/kg.