Synthesis and SAR studies of novel benzodiazepinedione-based inhibitors of Clostridium difficile (C. difficile) toxin B (TcdB).
Bioorg Med Chem Lett
; 28(23-24): 3601-3605, 2018 12 15.
Article
em En
| MEDLINE
| ID: mdl-30392779
ABSTRACT
Synthesis and structure-activity relationships (SAR) of a novel series of benzodiazepinedione-based inhibitors of Clostridium difficile toxin B (TcdB) are described. Compounds demonstrating low nanomolar affinity for TcdB, and which possess improved stability in mouse plasma vs. earlier compounds from this series, have been identified. Optimized compound 11d demonstrates a good pharmacokinetic (PK) profile in mouse and hamster and is efficacious in a hamster survival model of Clostridium difficile infection.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Proteínas de Bactérias
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Toxinas Bacterianas
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Benzodiazepinas
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Antibacterianos
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article