2. Academic Validation
  3. Discovery of a class of diheteroaromatic amines as orally bioavailable CDK1/4/6 inhibitors

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

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: huixin.wan@haihepharma.com.
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.

Figures