Journal of Medicinal Chemistry p. 1163 - 1170 (1990)
Update date:2022-07-31
Topics:
Hanko, Rudolf
Hammond, Michael D.
Fruchtmann, Romanis
Pfitzner, Joerg
Place, Graham A.
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.
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