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ID: ALA1806469

Journal: Eur J Med Chem

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

Authors: El-Gamal MI, Jung MH, Lee WS, Sim T, Yoo KH, Oh CH.

Abstract: 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 IC(50) in nanomolar range. In addition, compounds 8d, 8e, 8h, 9g, 9i, and 9j were more potent than Sorafenib but with IC(50) 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.

CiteXplore: 21592628

DOI: 10.1016/j.ejmech.2011.04.031