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Structure-Activity Relationship for the Oxadiazole Class of Antibacterials.

ABSTRACT: 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.

SUBMITTER: Boudreau MA

PROVIDER: S-EPMC7073871 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Structure-Activity Relationship for the Oxadiazole Class of Antibacterials.

Boudreau Marc A MA Ding Derong D Meisel Jayda E JE Janardhanan Jeshina J Spink Edward E Peng Zhihong Z Qian Yuanyuan Y Yamaguchi Takao T Testero Sebastian A SA O'Daniel Peter I PI Leemans Erika E Lastochkin Elena E Song Wei W Schroeder Valerie A VA Wolter William R WR Suckow Mark A MA Mobashery Shahriar S Chang Mayland M

ACS medicinal chemistry letters 20191003 3

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 antibacteria ...[more]

PMID: 32184964

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