Inflammatory bowel disease (IBD) is a chronic and recurrent inflammatory disease that with a relapsing and remitting course. There is an urgent demand for novel drugs to treat IBD with better efficacy and fewer side effects. CXCR4/CXCL12 axis plays a constitutive and inflammatory role in the intestinal mucosa, resulting in the chemotaxis of plenty of inflammatory cells to the intestine. Modulating this chemotactic axis by CXCR4 modulators may lead to the discovery of more effective anti-IBD candidates. Taking the secondary amine as the lead structure, a series of bisamide CXCR4 modulators with various substituents are designed, synthesized, and evaluated for the ameliorating effects on acute inflammation and IBD. Among them, compound Im effectively alleviates TNBS-induced IBD and reduces the number of inflammatory cells and the secretion of inflammatory factors in the intestinal mucosa. The obtained results indicate that CXCR4 is a potential anti-IBD target, and design of potent CXCR4 modulators is an optional strategy to discover novel anti-IBD candidates with different mechanisms.

中文翻译：

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Bisamide CXCR4 调节剂：作用于炎症细胞趋化性的新型抗 IBD 剂

炎症性肠病（IBD）是一种慢性和复发性炎症性疾病，具有复发和缓解过程。迫切需要治疗IBD疗效更好、副作用更少的新药。CXCR4/CXCL12轴在肠黏膜中发挥组成性和炎症作用，导致大量炎症细胞向肠道趋化。通过 CXCR4 调节剂调节这种趋化轴可能会导致发现更有效的抗 IBD 候选物。以仲胺为先导结构，设计、合成了一系列具有多种取代基的双酰胺CXCR4调节剂，并评价其对急性炎症和IBD的改善作用。其中，化合物Im有效缓解TNBS诱导的IBD，减少肠黏膜炎症细胞的数量和炎症因子的分泌。所得结果表明 CXCR4 是一种潜在的抗 IBD 靶标，设计有效的 CXCR4 调节剂是发现具有不同机制的新型抗 IBD 候选物的可选策略。