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

…, MD Hammond, R Fruchtmann, J Pfitzner…

Index: Hanko, Rudolf; Hammond, Michael D.; Fruchtmann, Romanis; Pfitzner, Joerg; Place, Graham A. Journal of Medicinal Chemistry, 1990 , vol. 33, # 4 p. 1163 - 1170

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Citation Number: 12

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 ICx, of 1.8 pM in vitro. LTCl release was inhibited by 80% after intraperitoneal ...