CXCR4 and its cognate ligand CXCL12 has been linked to various pathways such as cancer metastasis, inflammation, HIV-1 proliferation, and auto-immune diseases. Small molecules have shown potential as CXCR4 inhibitors and modulators, and therefore can mitigate diseases related to the CXCR4-CXCL12 pathway. We have designed and synthesized a series of 2,5-diamino and 2,5-dianilinomethyl pyridine derivatives as potential CXCR4 antagonists. Thirteen compounds have an effective concentration (EC) of 100 nM or less in a binding affinity assay and nine of these have at least 75% inhibition of invasion in Matrigel binding assay. Compounds 3l, 7f, 7j, and 7p show a minimal reduction in inflammation when carrageenan paw edema test is conducted. Overall, these compounds show potential as CXCR4 antagonist.

CXCR4及其同源配体CXCL12已与多种途径相关，例如癌症转移，炎症，HIV-1增殖和自身免疫性疾病。小分子已显示出作为CXCR4抑制剂和调节剂的潜力，因此可以缓解与CXCR4-CXCL12途径有关的疾病。我们已经设计和合成了一系列2，5-二氨基和2，5-二苯胺基甲基吡啶衍生物作为潜在的CXCR4拮抗剂。在结合亲和力测定中有13种化合物的有效浓度（EC）为100 nM或更小，其中9种在基质胶结合测定中具有至少75％的浸润抑制作用。化合物3l，7f，7j和7p进行角叉菜胶爪水肿试验时，炎症反应最小。总之，这些化合物显示出作为CXCR4拮抗剂的潜力。