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.

中文翻译：

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识别和的抑制剂的初始优化艰难梭菌（艰难梭菌）毒素B（TcdB的）

一类新的抑制剂的发现，合成和初步结构-活性关系（SAR）艰难梭菌（艰难梭菌）毒素B（TcdB的）进行说明。一种高通量筛选（HTS）运动导致中等活性筛选命中的标识1 - 5，其最有效的是化合物1（IC ₅₀  = 0.77微米）。在计算机对接中，早期的类似物为结构修饰提供了建议，从而导致设计和合成了高效的类似物13j（IC ₅₀  = 1 nM）和13 l（IC ₅₀ = 7 nM）作为进一步优化的线索。