Discovery of a class of diheteroaromatic amines as orally bioavailable CDK1/4/6 inhibitors

  • Bioorg Med Chem Lett. 2017 Dec 1;27(23):5332-5336. doi: 10.1016/j.bmcl.2017.09.050.
Yan Fu  1 ,  Shuai Tang  2 ,  Yi Su  2 ,  Xiaojing Lan  2 ,  Yan Ye  1 ,  Chuantao Zha  1 ,  Lei Li  1 ,  Jianhua Cao  1 ,  Yi Chen  2 ,  Lei Jiang  1 ,  Ying Huang  1 ,  Jian Ding  2 ,  Meiyu Geng  2 ,  Min Huang  2 ,  Huixin Wan  3
Affiliations
  • 1. Shanghai HaiHe Pharmaceutial, Co., Ltd., No. 421 Newton Road, Zhangjiang Hi-tech Park, Pudong New Area, Shanghai 201203, China.
  • 2. Shanghai Institute of Materia Medica, Chinese Academy of Science, No. 555 Zuchongzhi Road, Zhangjiang Hi-tech Park, Pudong New Area, Shanghai 201203, China.
  • 3. Shanghai HaiHe Pharmaceutial, Co., Ltd., No. 421 Newton Road, Zhangjiang Hi-tech Park, Pudong New Area, Shanghai 201203, China. Electronic address: [email protected].
PMID: 29074254 DOI: 10.1016/j.bmcl.2017.09.050
Abstract

The discovery of a class of diheteroaromatic amines based on LY2835219 as cyclin-dependent kinase (CDK1/4/6) inhibitors was described. The series was found to have much more improved CDK1 inhibition and potent in vitro anti-proliferative effects against Cancer cell lines. The synthesis and structure-activity relationship studies of these compounds were reported. One promising compound was selected to evaluate as a novel lead compound after in vitro and in vivo profiling.

Keywords
CDK inhibitor; Cyclin-dependent kinase; In vitro and in vivo profiling; Structure-activity relationship.