SAR studies leading to the identification of a novel series of metallo-β-lactamase inhibitors for the treatment of carbapenem-resistant Enterobacteriaceae infections that display efficacy in an animal infection model.

The clinical effectiveness of carbapenem antibiotics such as meropenem is becoming increasingly compromised by the spread of both metallo β-lactamase (MBL) and serine β-lactamase (SBL) enzymes on mobile genetic elements, stimulating research to find new β-lactamase inhibitors to be used in conjunction with carbapenems and other β-lactam antibiotics. Herein we describe our initial exploration of a novel chemical series of metallo β-lactamase inhibitors, from concept through to efficacy in a survival model using an advanced tool compound (ANT431) in conjunction with meropenem.