|
|||||
|
|
Synthesis and SAR studies of novel benzodiazepinedione-based inhibitors of Clostridium difficile (C. difficile) toxin B (TcdB) |
|
| Authors: | Jeffrey J Letourneau Ilana L Stroke David W Hilbert Andrew G Cole Laurie J Sturzenbecker Brett A Marinelli Jorge G Quintero Joan Sabalski Yanfang Li Linh Ma Igor Pechik Philip D Stein Maria L Webb |
| Institution: | 1. Venenum Biodesign, a member of Genesis Biotechnology Group, 8 Black Forest Road, Hamilton, NJ 08691, USA;2. Femeris Women’s Health Research Center, a member of Genesis Biotechnology Group, 2000 Waterview Drive, Hamilton, NJ 08691, USA |
| 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. |
| Keywords: | Clostridium difficile Toxin TcdB Inhibitor Corresponding author |
| 本文献已被 ScienceDirect 等数据库收录！ | |