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

  • Bioorg Med Chem Lett. 2014 Jun 1;24(11):2555-9. doi: 10.1016/j.bmcl.2014.03.086.
Hejun Lu  1 ,  Wangyang Tu  2 ,  Hongbo Fei  2 ,  Guoji Xu  2 ,  Qiyue Hu  2 ,  Lei Zhang  2 ,  Bing Lin  2 ,  Jijun Yuan  2 ,  Junzhao Yin  2 ,  Aishen Gong  2 ,  Mimi Wan  2 ,  Dan Wang  2 ,  Xiaoyan Zhu  2 ,  Jun Feng  2 ,  Qian Wang  2 ,  Piaoyang Sun  2
Affiliations
  • 1. Shanghai Hengrui Pharmaceutical Co., Ltd, 279 Wenjing Rd., Minhang District, Shanghai 200245, China. Electronic address: [email protected].
  • 2. Shanghai Hengrui Pharmaceutical Co., Ltd, 279 Wenjing Rd., Minhang District, Shanghai 200245, China.
PMID: 24755426 DOI: 10.1016/j.bmcl.2014.03.086
Abstract

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.

Keywords
Bicyclic; Cancer; Fused-pyridine; MEK; SBDD.