874143-26-7Relevant articles and documents
Method for synthesizing diarylamine by optical/nickel concerted catalysis
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Paragraph 0046; 0047; 0048; 0049; 0148; 0149; 0150; 0151, (2018/09/08)
The invention discloses a method for synthesizing diarylamine by optical/nickel concerted catalysis. According to the method, a ligand does not need to be added, and simple and cheap nickel salt is directly used as a metal catalyst to cooperate with a photosensitizer to catalyze arylamine and aryl bromide to generate cross-coupling. The method has the following advantages: (1) the use amount of BODIPY type organic photocatalyst is low, and the BODIPY type organic photocatalyst has a better catalysis effect in comparison with metal iridium and ruthenium photocatalysts reported in the literature; (2) the BODIPY type organic photocatalyst is easy for synthesis; (3) the use amount of nickel salt is few, and the ligand does not need to be added; and (4) the reaction conditions are mild, and theyield of most coupling products is higher than 90%. According to the method disclosed by the invention, high temperature and high pressure equipment is not needed, temperature change scope is small,experimental procedure is simple and easy to operate, and the method has a relatively high application value and industrial popularization potential.
Novel inhibitors of the v-raf murine sarcoma viral oncogene homologue B1 (BRAF) based on a 2,6-disubstituted pyrazine scaffold
Niculescu-Duvaz, Ion,Roman, Esteban,Whittaker, Steven R.,Friedlos, Frank,Kirk, Ruth,Scanlon, Ian J.,Davies, Lawrence C.,Niculescu-Duvaz, Dan,Marais, Richard,Springer, Caroline J.
scheme or table, p. 3261 - 3274 (2009/04/06)
BRAF, a serine/threonine kinase, plays a key role in the development of certain types of cancer, particularly melanoma. 2-(3,4,5-Trimethoxyphenylamino)- 6-(3-acetamidophenyl)-pyrazine, 1, was identified as a low micromolar (IC 50 = 3.5 μM) BRAF inhibitor from a high-throughput screen of a library of 23000 compounds. This compound was chosen as the starting point of a program aimed at developing inhibitors of mutant V600EBRAF. We have already reported on the optimization of the trimethoxyphenylamino moiety of 1. In this paper, we describe the synthesis of a series of compounds derived from 1 with the purpose of optimization of the pyrazine central core and the phenylacetamido moiety in order to increase the potency against V600EBRAF compared to CRAF. The biological activity of the new inhibitors was assessed against mutant V600EBRAF in vitro several compounds were identified with IC50s of 300-500 nM for V600EBRAF, and all compounds that were assessed showed selectivity for V600EBRAF compared to CRAF by 5->86-fold.
