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

  • Bioorg Med Chem. 2011 Mar 15;19(6):1915-23. doi: 10.1016/j.bmc.2011.01.067.
Mi-hyun Kim  1 ,  Minjung Kim ,  Hana Yu ,  Hwan Kim ,  Kyung Ho Yoo ,  Taebo Sim ,  Jung-Mi Hah
Affiliations
  • 1. Department of Pharmacy, College of Pharmacy, Hanyang University, 1271 Sa 3-Dong, Sangnok-gu, Ansan-si, Gyunggi-do 426-791, South Korea.
PMID: 21353571 DOI: 10.1016/j.bmc.2011.01.067
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 (GI(50)=0.27 μM). Especially, 7c was found to be a potent and selective B-Raf V600E and C-Raf Inhibitor (IC(50)=0.26 μM, IC(50)=0.11 μM, respectively), showing a possibility as melanoma therapeutics.