Design, synthesis, and antiproliferative activity of new 1H-pyrrolo[3,2-c]pyridine derivatives against melanoma cell lines. Part 2

Abstract

A new series of diarylureas and diarylamides possessing 1H-pyrrolo[3,2-c]pyridine scaffold was designed and synthesized. Their in vitro antiproliferative activities against A375P human melanoma cell line and NCI-9 human melanoma cell line panel were tested. All the target compounds, except three amino derivatives 8g, h and 9h, demonstrated superior potencies against A375P to Sorafenib. In addition, compounds 8a and 9b–f demonstrated higher potencies than Vemurafenib against A375P. Compounds 8c and 9b were 7.50 and 454.90 times, respectively, more selective towards A375P melanoma cells over NIH3T3 fibroblasts. Furthermore, compounds 8d, e and 9a–d, f demonstrated very high potencies against the nine tested melanoma cell lines at the NCI. The bisamide derivatives 9a–c, f showed 2-digit nanomolar IC50 values over different cell lines of the NCI-9 melanoma cell lines.