Potent and selective Candida albicans N-myristoyltransferase (CaNmt) inhibi
tors have been identified through optimization of a lead compound 1 discove
red by random screening. The inhibitor design is based on the crystal struc
ture of the CaNmt complex with compound (S)-3 and structure-activity relati
onships (SARs) have been clarified. Modification of the C-4 side chain of 1
has led to thr discovery of a potent and selective CaNmt inhibitor 11 (RO-
09-4609), which exhibits antifungal activity against C. albicans in vitro,
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