Discovery of VNRX-7145 (VNRX-5236 Etzadroxil): An Orally Bioavailable β-Lactamase Inhibitor for Enterobacterales Expressing Ambler Class A, C, and D Enzymes.
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
22 07 2021
22 07 2021
Historique:
pubmed:
1
7
2021
medline:
7
10
2021
entrez:
30
6
2021
Statut:
ppublish
Résumé
A major antimicrobial resistance mechanism in Gram-negative bacteria is the production of β-lactamase enzymes. The increasing emergence of β-lactamase-producing multi-drug-resistant "superbugs" has resulted in increases in costly hospital Emergency Department (ED) visits and hospitalizations due to the requirement for parenteral antibiotic therapy for infections caused by these difficult-to-treat bacteria. To address the lack of outpatient treatment, we initiated an iterative program combining medicinal chemistry, biochemical testing, microbiological profiling, and evaluation of oral pharmacokinetics. Lead optimization focusing on multiple smaller, more lipophilic active compounds, followed by an exploration of oral bioavailability of a variety of their respective prodrugs, provided
Identifiants
pubmed: 34191513
doi: 10.1021/acs.jmedchem.1c00437
pmc: PMC8311649
doi:
Substances chimiques
Anti-Bacterial Agents
0
beta-Lactamase Inhibitors
0
beta-Lactamases
EC 3.5.2.6
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
10155-10166Subventions
Organisme : NIAID NIH HHS
ID : R43 AI109879
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI111539
Pays : United States
Organisme : NIAID NIH HHS
ID : R44 AI109879
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI089512
Pays : United States
Organisme : NIAID NIH HHS
ID : HHSN272201600029C
Pays : United States
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