Structure based design and syntheses of amino-1H-pyrazole amide derivatives as selective Raf kinase inhibitors in melanoma cells

Mi Hyun Kim, Minjung Kim, Hana Yu, Hwan Kim, Kyung Ho Yoo, Taebo Sim, Jung Mi Hah

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The synthesis of a novel series of N-(5-amino-1-(4-methoxybenzyl)-1H- pyrazol-4-yl amide derivatives 6a-o, 7a-s and their antiproliferative activities against A375P melanoma cell line were described. Most compounds showed competitive antiproliferative activities to sorafenib, the reference standard. Among them, N-(5-amino-1-(4-methoxybenzyl)-1H-pyrazol-4-yl)-5-(3-(4-chloro-3- (trifluoromethyl)phenyl) ureido)-2-methylbenzamide 7c exhibited potent activities (GI50 = 0.27 μM). Especially, 7c was found to be a potent and selective B-Raf V600E and C-Raf inhibitor (IC50 = 0.26 μM, IC50 = 0.11 μM, respectively), showing a possibility as melanoma therapeutics.

Original languageEnglish
Pages (from-to)1915-1923
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume19
Issue number6
DOIs
Publication statusPublished - 2011 Mar 15

    Fingerprint

Keywords

  • Aminopyrazole amide
  • Antiproliferative activity
  • Kinase inhibitor
  • Kinase selectivity
  • Melanoma cell line

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this