info:eu-repo/semantics/article
Structure-Activity Relationship for the Oxadiazole Class of Antibacterials
Fecha
2020-03Registro en:
Boudreau, Marc A.; Ding, Derong; Meisel, Jayda E.; Janardhanan, Jeshina; Spink, Edward; et al.; Structure-Activity Relationship for the Oxadiazole Class of Antibacterials; American Chemical Society; ACS Medicinal Chemistry Letters; 11; 3; 3-2020; 322-326
1948-5875
CONICET Digital
CONICET
Autor
Boudreau, Marc A.
Ding, Derong
Meisel, Jayda E.
Janardhanan, Jeshina
Spink, Edward
Peng, Zhihong
Qian, Yuanyuan
Yamaguchi, Takao
Testero, Sebastian Andres
O'Daniel, Peter I.
Leemans, Erika
Lastochkin, Elena
Song, Wei
Schroeder, Valerie A.
Wolter, William R.
Suckow, Mark A.
Mobashery, Shahriar
Chang, Mayland
Resumen
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.