TY - JOUR
T1 - Discovery of a new class of non-β-lactam inhibitors of penicillin-binding proteins with gram-positive antibacterial activity
AU - O'Daniel, Peter I.
AU - Peng, Zhihong
AU - Pi, Hualiang
AU - Testero, Sebastian A.
AU - Ding, Derong
AU - Spink, Edward
AU - Leemans, Erika
AU - Boudreau, Marc A.
AU - Yamaguchi, Takao
AU - Schroeder, Valerie A.
AU - Wolter, William R.
AU - Llarrull, Leticia I.
AU - Song, Wei
AU - Lastochkin, Elena
AU - Kumarasiri, Malika
AU - Antunes, Nuno T.
AU - Espahbodi, Mana
AU - Lichtenwalter, Katerina
AU - Suckow, Mark A.
AU - Vakulenko, Sergei
AU - Mobashery, Shahriar
AU - Chang, Mayland
PY - 2014/3/5
Y1 - 2014/3/5
N2 - Infections caused by hard-to-treat methicillin-resistant Staphylococcus aureus (MRSA) are a serious global public-health concern, as MRSA has become broadly resistant to many classes of antibiotics. We disclose herein the discovery of a new class of non-β-lactam antibiotics, the oxadiazoles, which inhibit penicillin-binding protein 2a (PBP2a) of MRSA. The oxadiazoles show bactericidal activity against vancomycin-and linezolid-resistant MRSA and other Gram-positive bacterial strains, in vivo efficacy in a mouse model of infection, and have 100% oral bioavailability.
AB - Infections caused by hard-to-treat methicillin-resistant Staphylococcus aureus (MRSA) are a serious global public-health concern, as MRSA has become broadly resistant to many classes of antibiotics. We disclose herein the discovery of a new class of non-β-lactam antibiotics, the oxadiazoles, which inhibit penicillin-binding protein 2a (PBP2a) of MRSA. The oxadiazoles show bactericidal activity against vancomycin-and linezolid-resistant MRSA and other Gram-positive bacterial strains, in vivo efficacy in a mouse model of infection, and have 100% oral bioavailability.
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U2 - 10.1021/ja500053x
DO - 10.1021/ja500053x
M3 - Article
C2 - 24517363
AN - SCOPUS:84897696562
SN - 0002-7863
VL - 136
SP - 3664
EP - 3672
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 9
ER -