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Desmethyl Macrolides: Synthesis and Evaluation of 4,10-Didesmethyl Telithromycin

Novel sources of antibiotics are required to keep pace with the inevitable onset of bacterial resistance. Continuing with our macrolide desmethylation strategy as a source of new antibiotics, we report the total synthesis, molecular modeling, and biological evaluation of 4,10-didesmethyl telithromyc...

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Published in:ACS medicinal chemistry letters 2012-03, Vol.3 (3), p.211-215
Main Authors: Velvadapu, Venkata, Glassford, Ian, Lee, Miseon, Paul, Tapas, DeBrosse, Charles, Klepacki, Dorota, Small, Meagan C, MacKerell, Alexander D, Andrade, Rodrigo B
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cited_by cdi_FETCH-LOGICAL-a405t-25970615a6135a86e5602de7831ad546e26a519cd17509df59a3de1ddc5e91ee3
cites cdi_FETCH-LOGICAL-a405t-25970615a6135a86e5602de7831ad546e26a519cd17509df59a3de1ddc5e91ee3
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container_start_page 211
container_title ACS medicinal chemistry letters
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creator Velvadapu, Venkata
Glassford, Ian
Lee, Miseon
Paul, Tapas
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Small, Meagan C
MacKerell, Alexander D
Andrade, Rodrigo B
description Novel sources of antibiotics are required to keep pace with the inevitable onset of bacterial resistance. Continuing with our macrolide desmethylation strategy as a source of new antibiotics, we report the total synthesis, molecular modeling, and biological evaluation of 4,10-didesmethyl telithromycin (4), a novel desmethyl analogue of the third-generation drug telithromycin (2). Telithromycin is an FDA-approved ketolide antibiotic derived from erythromycin (1). We found 4,10-didesmethyl telithromycin (4) to be four times more active than previously prepared 4,8,10-tridesmethyl congener (3) in MIC assays. While less potent than telithromycin (2), the inclusion of the C-8 methyl group has improved biological activity, suggesting that it plays an important role in antibiotic function.
doi_str_mv 10.1021/ml200254h
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source American Chemical Society:Jisc Collections:American Chemical Society Read & Publish Agreement 2022-2024 (Reading list); PubMed Central
subjects Letter
title Desmethyl Macrolides: Synthesis and Evaluation of 4,10-Didesmethyl Telithromycin
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