New diarylamides and diarylureas possessing 8-amino(acetamido) quinoline scaffold: Synthesis, antiproliferative activities against melanoma cell lines, kinase inhibition, and in silico studies

Authors
Koh, Eun JeongEl-Gamal, Mohammed I.Oh, Chang-HyunLee, So HaSim, TaeboKim, GaramChoi, Hong SeokHong, Jun HeeLee, Sang-giYoo, Kyung Ho
Issue Date
2013-12
Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
Citation
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v.70, pp.10 - 21
Abstract
Synthesis of a new series of diarylureas and diarylamides possessing 4-aryl-8-amino(acetamido)quinoline scaffold is described. Their in vitro antiproliferative activities against ten melanoma cell lines were tested. Compounds 11, 21, 3c, and 4c showed the highest potency against A375P cell line with IC50 values in sub-micromolar scale. Compound 4c was equipotent to Vemurafenib against A375P. In addition, compounds 11, 2a, and 21 showed high potency over the NCI-9 tested melanoma cell line panel. The IC50 values of compounds 11 and 21 were in 2-digit nanomolar scale over four and five cell lines, respectively. Compound 21 showed high, dose-dependent inhibition of ERK kinase. ADME profiling showed that compounds 11, 21, 3c, 4c, and 5b are estimated to be orally bioavailable. (C) 2013 Elsevier Masson SAS. All rights reserved.
Keywords
DERIVATIVES; DESIGN; DISCOVERY; DIAGNOSIS; THERAPY; BRAF; DERIVATIVES; DESIGN; DISCOVERY; DIAGNOSIS; THERAPY; BRAF; Antiproliferative activity; Diarylamide; Diarylurea; ERK kinase; Melanoma; Quinoline
ISSN
0223-5234
URI
https://pubs.kist.re.kr/handle/201004/127400
DOI
10.1016/j.ejmech.2013.06.060
Appears in Collections:
KIST Article > 2013
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