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

• DOI: 10.1021/acsinfecdis.8b00246
• Publication Date: 2018-11-14T21:25:52Z
• Authors: Simon Leiris; Alicia Coelho; Jérôme Castandet; Maëlle Bayet; Clarisse Lozano; Juliette Bougnon; Justine Bousquet; Martin Everett; Marc Lemonnier; Nicolas Sprynski; Magdalena Zalacain; Thomas David Pallin; Michael C. Cramp; Neil Jennings; Gilles Raphy; Mark W. Jones; Ramesh Pattipati; Battu Shankar; Relangi Sivasubra...; Ashok K. Soodhagani; Ramakrishna R. Ju...; Narender Pottabat...; Srinivasu Pothuka...; Manuela Benvenuti; Cecilia Pozzi; Stefano Mangani; Filomena De Luca; Giulia Cerboni; Jean-Denis Docquier; David T. Davies
• Keywords: Carbapenem; Carbapenem-resistant enterobacteriaceae

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