1. Venenum Biodesign, Genesis Biotechnology Group, 8 Black Forest Road, Hamilton, NJ 08691, USA;2. Femeris Women’s Health Research Center, Genesis Biotechnology Group, 2000 Waterview Drive, Hamilton, NJ 08691, USA
Abstract:
The discovery, synthesis and preliminary structure-activity relationship (SAR) of a novel class of inhibitors of Clostridium difficile (C. difficile) toxin B (TcdB) is described. A high throughput screening (HTS) campaign resulted in the identification of moderately active screening hits 1–5 the most potent of which was compound 1 (IC50?=?0.77?µM). In silico docking of an early analog offered suggestions for structural modification which resulted in the design and synthesis of highly potent analogs 13j(IC50?=?1?nM) and 13?l(IC50?=?7?nM) which were chosen as leads for further optimization.