N-Acyloxymethyl carbamate linked prodrugs of pseudomycins are novel antifungal agents

We describe herein the synthesis, bioconversion, antifungal activity, and p reliminary toxicology evaluation of a series of N-acyloxymethyl carbamate l inked triprodrugs of pseudomycins. The syntheses of these prodrugs (3-6) we re achieved via simple N-acylation of PSB (1) or PSC ' (2) with various pro drug linkers (7-9). As expected, upon incubation with mouse and/or human pl asma, many of these prodrugs (3, 5, and 6) were converted to the parent com pound within a few hours. Of particular significance, two pseudomycin tripr odrugs (5 and 6) showed excellent in vivo efficacy against systemic Candidi asis without tail vein irritation being observed. (C) 2001 Elsevier Science Ltd. All rights reserved.