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 language | English |
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Pages (from-to) | 1915-1923 |
Number of pages | 9 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 19 |
Issue number | 6 |
DOIs | |
Publication status | Published - 2011 Mar 15 |
Bibliographical note
Funding Information:This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology ( 2009-0087992 ; J.M.H.). We also thank Professor Hye Hyun Yoo in Hanyang University for HRMS data acquisition and interpretation.
Keywords
- Aminopyrazole amide
- Antiproliferative activity
- Kinase inhibitor
- Kinase selectivity
- Melanoma cell line
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry