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Published on: May 2, 2018
Development of a 3-Amino-1-carboxymethyl-β-lactam-Based Monocyclic Ceftobiprole Analog
Kato Bredael1, Martina Hrast Rambaher2, Lena Decuyper1
1SynBioC Research Group, Department of Green Chemistry and Technology, Faculty of Bioscience Engineering, Ghent University, Ghent, Belgium.
Abstract:
Antimicrobial resistance is a major and growing global health challenge, necessitating the development of novel antibacterial agents. Previous in-house research identified monocyclic α-benzylidene-substituted 3-amino-1-carboxymethyl-β-lactams as promising hit scaffolds due to their potential to inhibit penicillin-binding proteins (PBPs). In this study, a new ceftobiprole analog was designed by combining the characteristic α-alkylidene fragment from this hit scaffold with the ceftobiprole vinylpyrrolidinone side chain selected for its favorable pharmacological properties. The target structure was synthesized via a modular approach, employing two Wittig reactions as key steps. Biochemical evaluation revealed that the ethyl ester derivative exhibited significant inhibition of S. pneumoniae PBP1b, highlighting this new framework as a valuable starting point for further optimization.
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