Structure-based design and synthesis of bicyclic fused-pyridines as MEK inhibitors.

Bioorg Med Chem Lett

Shanghai Hengrui Pharmaceutical Co., Ltd, 279 Wenjing Rd., Minhang District, Shanghai 200245, China.

Published: June 2014

The MAPK pathway is identified as one of the most important pathways involved in cell proliferation and differentiation. A key kinase in the pathway, the Mitogen-activated protein kinase kinase (MEK) is recognized as a promising target for antitumor drugs. Structure-based design and optimization of known MEK inhibitors resulted in identification of compound 10a as a potent non-ATP competitive MEK inhibitor in both in vitro and in vivo tests.

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http://dx.doi.org/10.1016/j.bmcl.2014.03.086DOI Listing

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