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ID: ALA1136983

Journal: Bioorg Med Chem Lett

Title: Synthesis, cleavage, and antifungal activity of a number of novel, water-soluble ester prodrugs of antifungal triazole CS-758.

Authors: Kagoshima Y, Mori M, Suzuki E, Shibayama T, Iida T, Kamai Y, Konosu T.

Abstract: In this study, the synthesis and evaluation of a number of esters of CS-758 as injectable prodrugs are described. Phosphoryl ester 1a was soluble in water (>30mg/mL) and was converted to CS-758 in human liver microsome. It was also converted to CS-758 in rats after iv administration, wherein the bioavailability of CS-758 was 53%. Compound 1a (iv) reduced the viable cell counts in kidneys in a murine systemic Candida albicans infection model, wherein the effect was comparable to or slightly superior to that of CS-758 (po). The prodrug 1a proved to be a promising injectable antifungal agent whose further evaluation is warranted.

CiteXplore: 19467867

DOI: 10.1016/j.bmcl.2009.04.135