956488-03-2Relevant articles and documents
BRAF inhibitors based on an imidazo[4,5]pyridin-2-one scaffold and a meta substituted middle ring
Nourry, Arnaud,Zambon, Alfonso,Davies, Lawrence,Niculescu-Duvaz, Ion,Dijkstra, Harmen P.,Ménard, Delphine,Gaulon, Catherine,Niculescu-Duvaz, Dan,Suijkerbuijk, Bart M. J. M.,Manne, Frank Friedlos Helen A.,Kirk, Ruth,Whittaker, Steven,Marais, Richard,Springer, Caroline J.
supporting information; experimental part, p. 1964 - 1978 (2010/08/05)
We recently reported on the development of a novel series of BRAF inhibitors based on a tripartite A-B-C system characterized by a para-substituted central aromatic core connected to an imidazo[4,5]pyridin-2-one scaffold and a substituted urea linker. Here, we present a new series of BRAF inhibitors in which the central phenyl ring connects to the hinge binder and substrate pocket of BRAF with a meta-substitution pattern. The optimization of this new scaffold led to the development of lownanomolar inhibitors that permits the use of a wider range of linkers and terminal C rings while enhancing the selectivity for the BRAF enzyme in comparison to the para series.
