1163720-86-2Relevant academic research and scientific papers
Novel hinge binder improves activity and pharmacokinetic properties of BRAF inhibitors
Zambon, Alfonso,Ménard, Delphine,Suijkerbuijk, Bart M. J. M.,Niculescu-Duvaz, Ion,Whittaker, Steven,Niculescu-Duvaz, Dan,Nourry, Arnaud,Davies, Lawrence,Manne, Helen A.,Lopes, Filipa,Preece, Natasha,Hedley, Douglas,Ogilvie, Lesley M.,Kirk, Ruth,Marais, Richard,Springer, Caroline J.
supporting information; experimental part, p. 5639 - 5655 (2010/10/03)
Mutated BRAF serine/threonine kinase is implicated in several types of cancer, with particularly high frequency in melanoma and colorectal carcinoma. We recently reported on the development of BRAF inhibitors based on a tripartite A?B?C system featuring an imidazo[4,5]pyridin-2-one group hinge binder. Here we present the design, synthesis, and optimization of a new series of inhibitors with a different A?B?C system that has been modified by the introduction of a range of novel hinge binders (A ring). The optimization of the hinge binding moiety has enabled the development of compounds with low nanomolar potencies in both BRAF inhibition and cellular assays. These compounds display optimal pharmacokinetic properties that warrant further in vivo investigations.
PYRIDO[2,3-B]PYRAZINE-8-SUBSTITUTED COMPOUNDS AND THEIR USE
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Page/Page column 112-113, (2009/07/18)
The present invention pertains generally to the field of therapeutic compounds for treating proliferative disorders, cancer, etc., and more specifically to certain pyrido[2,3-b]pyrazin-8-substituted compounds, as described herein, which, inter alia, inhibit RAF (e.g., B RAF) activity. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit RAF (e.g., BRAF) activity, to inhibit receptor tyrosine kinase (RTK) activity, to inhibit cell proliferation, and in the treatment of diseases and disorders that are ameliorated by the inhibition of RAF, RTK, etc., proliferative disorders such as cancer (e.g., colorectal cancer, melanoma), etc.
