| Literature DB >> 22185282 |
Bassam Abu Thaher1, Martina Arnsmann, Frank Totzke, Jan E Ehlert, Michael H G Kubbutat, Christoph Schächtele, Markus O Zimmermann, Pierre Koch, Frank M Boeckler, Stefan A Laufer.
Abstract
In the course of searching for new p38α MAP kinase inhibitors, we found that the regioisomeric switch from 3-(4-fluorophenyl)-4-(pyridin-4-yl)-1-(aryl)-1H-pyrazol-5-amine to 4-(4-fluorophenyl)-3-(pyridin-4-yl)-1-(aryl)-1H-pyrazol-5-amine led to an almost complete loss of p38α inhibition, but they showed activity against important cancer kinases. Among the tested derivatives, 4-(4-fluorophenyl)-3-(pyridin-4-yl)-1-(2,4,6-trichlorophenyl)-1H-pyrazol-5-amine (6a) exhibited the best activity, with IC(50) in the nanomolar range against Src, B-Raf wt, B-Raf V600E, EGFRs, and VEGFR-2, making it a good lead for novel anticancer programs.Entities:
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Year: 2012 PMID： 22185282 DOI： 10.1021/jm201391u
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446