| Autor: |
JoAnne Dzink-Fox, Jason T. Brewer, Esther K. Schmitt, Karl Dean, Matthew J. LaMarche, Stacey Tiamfook, Gabe Gamber, Zachary Robinson, Jennifer A. Leeds, Michael A. Patane, Deborah Palestrant, Colin Osborne, Franco Lombardo, Akash K. Jain, David McKenney, Jian Ding, Lewis Whitehead, Philipp Krastel, Elin M. Rann, Travis Stams, Donghui Yu, Ryan Kerrigan, Georg Neckermann, Kwangho Lee |
| Rok vydání: |
2016 |
| Předmět: |
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| Zdroj: |
Journal of medicinal chemistry. 59(14) |
| ISSN: |
1520-4804 |
| Popis: |
Synthetic studies of the antimicrobial secondary metabolite thiomuracin A (1) provided access to analogues in the Northern region (C2–C10). Selective hydrolysis of the C10 amide of lead compound 2 and subsequent derivatization led to novel carbon- and nitrogen-linked analogues (e.g., 3) which improved antibacterial potency across a panel of Gram-positive organisms. In addition, congeners with improved physicochemical properties were identified which proved efficacious in murine sepsis and hamster C. difficile models of disease. Optimal efficacy in the hamster model of C. difficile was achieved with compounds that possessed both potent antibacterial activity and high aqueous solubility. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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