Microwave-accelerated synthesis of protease inhibitors

Abstract

Controlled microwave heating has recently emerged as an enabling and productivity-enhancing tool for the medicinal chemist. With this superheating method, reaction times can often be reduced from days and hours down to minutes, and chemistry previously considered impractical or unattainable can be accessed. In this review, the search for new protease inhibitors using microwave-assisted small-scale organic transformations is presented, with a special focus on the development of inhibitors of the aspartic proteases plasmepsin I, plasmepsin II, and HIV-1 protease. A series of rapid lead-optimizations starting from transition-state mimicking core scaffolds using mainly microwave-accelerated, palladium-catalyzed coupling reactions are presented. Biological background and test results are summarized. © Springer-Verlag 2006.