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Published on: February 14, 2018
Prodrugs of 3-amido bearing pseudomycin analogues: novel antifungal agents
1Lilly Research Laboratory, A Division of Eli Lilly and Company, Lilly Corporate Center, IN 46285, Indianapolis, USA.
Abstract:
With the aim of identifying safer pseudomycin derivatives, we synthesized and evaluated a number of N-acyloxymethyl carbamate linked prodrugs of 3-amido pseudomycin analogues. To our satisfaction, all of the prodrug-amide combinations prepared exhibited good in vivo efficacy against murine Candidiasis. When evaluated in a dose elevation study, all of the newly synthesized combinations (e.g., 4A, 6A, 8A, and 8B) demonstrated improved toxicity profiles in comparison to their corresponding 3-amides as well as the parent pseudomycin B.
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