Exploration of the Structure-Activity Relationship of 1,2,4-Oxadiazole Antibiotics

DERONG DING; MARC A. BOUDREAU; ERIKA J. LEEMANS; EDWARD SPINK; TAKAO YAMAGUCHI; SEBASTIAN A. TESTERO; PETER I. ODANIEL; ELENA LASTOCHKIN; MAYLAND CHANG; SHAHRIAR MOBASHERY

BIORGANIC AND MEDICINAL CHEMISTRY LETTERS

Elsevier

Año: 2015 vol. 25 p. 4854 - 4857

0960-894X

We have recently disclosed the discovery of the class of 1,2,4-oxadiazole antibiotics, which emerged from in silico docking and scoring efforts. This class of antibacterials exhibits Gram-positive activity, particularly against Staphylococcus aureus. We define the structure?activity relationship (SAR) of this class of antibiotics with the synthesis and evaluation of a series of 59 derivatives with variations in the C ring or C and D rings. A total of 17 compounds showed activity against S. aureus. Four derivatives were evaluated against a panel of 16 Gram-positive strains, inclusive of several methicillin-resistant S. aureus strains. These compounds are broadly active against Gram-positive bacteria.