| Literature DB >> 32420736 |
Joel A Goldberg1, Ha Nguyen2, Vijay Kumar2, Elizabeth J Spencer3, Denton Hoyer3, Emma K Marshall1, Anna Cmolik1, Margaret O'Shea1, Steven H Marshall1, Andrea M Hujer1,4, Kristine M Hujer1,4, Susan D Rudin1,4, T Nicholas Domitrovic1,4, Christopher R Bethel1, Krisztina M Papp-Wallace1,2,4, Latania K Logan5,6, Federico Perez1,4,7, Michael R Jacobs4,8, David van Duin9, Barry M Kreiswirth10, Robert A Bonomo1,2,4,7,11,12, Mark S Plummer3, Focco van den Akker2.
Abstract
Treatment of multidrug-resistant Gram-negative bacterial pathogens represents a critical clinical need. Here, we report a novel γ-lactam pyrazolidinone that targets penicillin-binding proteins (PBPs) and incorporates a siderophore moiety to facilitate uptake into the periplasm. The MIC values of γ-lactam YU253434, 1, are reported along with the finding that 1 is resistant to hydrolysis by all four classes of β-lactamases. The druglike characteristics and mouse PK data are described along with the X-ray crystal structure of 1 binding to its target PBP3.Entities:
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Year: 2020 PMID： 32420736 PMCID： PMC7590959 DOI： 10.1021/acs.jmedchem.0c00255
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446