Structure-Activity Relationship for the Oxadiazole Class of Antibacterials.

Autor:	Boudreau MA; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States., Ding D; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States., Meisel JE; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States., Janardhanan J; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States., Spink E; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States., Peng Z; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States., Qian Y; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States., Yamaguchi T; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States., Testero SA; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States., O'Daniel PI; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States., Leemans E; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States., Lastochkin E; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States., Song W; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States., Schroeder VA; Freimann Life Sciences Center and Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556, United States., Wolter WR; Freimann Life Sciences Center and Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556, United States., Suckow MA; Freimann Life Sciences Center and Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556, United States., Mobashery S; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States., Chang M; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States.
Jazyk:	angličtina
Zdroj:	ACS medicinal chemistry letters [ACS Med Chem Lett] 2019 Oct 03; Vol. 11 (3), pp. 322-326. Date of Electronic Publication: 2019 Oct 03 (Print Publication: 2020).
DOI:	10.1021/acsmedchemlett.9b00379
Abstrakt:	A structure-activity relationship (SAR) for the oxadiazole class of antibacterials was evaluated by syntheses of 72 analogs and determination of the minimal-inhibitory concentrations (MICs) against the ESKAPE panel of bacteria. Selected compounds were further evaluated for in vitro toxicity, plasma protein binding, pharmacokinetics (PK), and a mouse model of methicillin-resistant Staphylococcus aureus (MRSA) infection. Oxadiazole 72c shows potent in vitro antibacterial activity, exhibits low clearance, a high volume of distribution, and 41% oral bioavailability, and shows efficacy in mouse models of MRSA infection. Competing Interests: The authors declare no competing financial interest. (Copyright © 2019 American Chemical Society.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu