Synthesis and evaluation of novel pseudomycin side-chain analogues. Part 3.
To increase the therapeutic utility of C-18 side-chain bearing pseudomycin analogue 2, we prepared additional analogues and prodrugs of 2 containing further modifications at various positions within its core structure. Each of the newly synthesized derivatives (10-15) exhibited reduced tail vein toxicity relative to the parent compound. Some of the new pseudomycin derivatives (e.g., 14) also showed improved in vivo antifungal activity relative to its corresponding parent compound.
Sun
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Lilly Research Laboratories, A Division of Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA.
Zhang
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Zeckner
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Current
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Chen
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D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology*; D001671:Biochemistry / Q000379:methods; D002177:Candidiasis / Q000188:drug therapy; D004353:Drug Evaluation, Preclinical; D051379:Mice; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D018675:Toxicity Tests / Q000379:methods
D000935:Antifungal Agents; D010456:Peptides, Cyclic; C107665:pseudomycin A