Synthesis of a new series of diarylureas and diarylamides having 1H-pyrrolo[3,2-c]pyridine scaffold is described. Their in vitro antiproliferative activity against A375P human melanoma cell line was tested and the effect of substituents on pyrrolo[3,2-c]pyridine nucleus was investigated. The newly synthesized compounds, except three N-tolyl derivatives (8f, 9f, and 9h), generally showed superior activity against A375P to Sorafenib. Among all of these derivatives, compounds 8b, 8g, and 9a–e showed the highest potency against A375P with IC₅₀ in nanomolar range. In addition, compounds 8d, 8e, 8h, 9g, 9i, and 9j were more potent than Sorafenib but with IC₅₀ in micromolar range. Compounds 8b, 8g, 9b–d, and 9i demonstrated higher selectivity towards A375P compared with NIH3T3 fibroblasts. The most potent diarylurea 8g and diarylamide 9d were further tested and showed high potency over nine melanoma cell lines at the NCI.

描述了具有1 H-吡咯并[3,2- c ]吡啶骨架的一系列新的二芳基脲和二芳基酰胺的合成。测试了它们对A375P人黑素瘤细胞系的体外抗增殖活性，并研究了取代基对吡咯并[3,2- c ]吡啶核的影响。除了三个N-甲苯基衍生物（8f，9f和9h）以外，新合成的化合物通常对索拉非尼显示出对A375P的优异活性。在所有这些衍生物中，化合物8b，8g和9a–e在IC _50下显示出对A375P的最高效力在纳摩尔范围内。此外，化合物8d，8e，8h，9g，9i和9j比索拉非尼更有效，但IC ₅₀在微摩尔范围内。与NIH3T3成纤维细胞相比，化合物8b，8g，9b–d和9i对A375P的选择性更高。进一步测试了最有效的二芳基脲8g和二芳基酰胺9d，它们在NCI上显示出对九种黑色素瘤细胞系的高效力。