TY - JOUR
T1 - Structure-Activity Relationship for the Oxadiazole Class of Antibacterials
AU - Boudreau, Marc A.
AU - Ding, Derong
AU - Meisel, Jayda E.
AU - Janardhanan, Jeshina
AU - Spink, Edward
AU - Peng, Zhihong
AU - Qian, Yuanyuan
AU - Yamaguchi, Takao
AU - Testero, Sebastian A.
AU - O'Daniel, Peter I.
AU - Leemans, Erika
AU - Lastochkin, Elena
AU - Song, Wei
AU - Schroeder, Valerie A.
AU - Wolter, William R.
AU - Suckow, Mark A.
AU - Mobashery, Shahriar
AU - Chang, Mayland
N1 - Publisher Copyright:
Copyright © 2019 American Chemical Society.
PY - 2020/3/12
Y1 - 2020/3/12
N2 - 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.
AB - 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.
KW - Antibacterials
KW - oxadiazoles
KW - penicillin-binding proteins
KW - structure-activity relationship
UR - http://www.scopus.com/inward/record.url?scp=85073153216&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85073153216&partnerID=8YFLogxK
U2 - 10.1021/acsmedchemlett.9b00379
DO - 10.1021/acsmedchemlett.9b00379
M3 - Article
AN - SCOPUS:85073153216
VL - 11
SP - 322
EP - 326
JO - ACS Medicinal Chemistry Letters
JF - ACS Medicinal Chemistry Letters
IS - 3
ER -