2. Academic Validation
  3. Discovery of a novel series of imidazo[1',2':1,6]pyrido[2,3-d]pyrimidin derivatives as potent cyclin-dependent kinase 4/6 inhibitors

Discovery of a novel series of imidazo[1',2':1,6]pyrido[2,3-d]pyrimidin derivatives as potent cyclin-dependent kinase 4/6 inhibitors

  • Eur J Med Chem. 2020 May 1;193:112239. doi: 10.1016/j.ejmech.2020.112239.
Chen Shi 1,  Qian Wang 1,  Xuemei Liao 1,  Hui Ge 1,  Guoyong Huo 1,  Leduo Zhang 1,  Na Chen 1,  Xiong Zhai 1,  Yuan Hong 1,  Li Wang 1,  Zhe Wang 1,  Weijun Shi 1,  Yu Mao 1,  Jianxin Yu 1,  Ying Ke 2,  Guangxin Xia 3
Affiliations

Affiliations

  • 1 Central Research Institute, Shanghai Pharmaceuticals Holding Co., Ltd., Building 5, No. 898 Halei Road, Zhangjiang Hi-tech Park, Pudong New Area, Shanghai, 201203, PR China.
  • 2 Central Research Institute, Shanghai Pharmaceuticals Holding Co., Ltd., Building 5, No. 898 Halei Road, Zhangjiang Hi-tech Park, Pudong New Area, Shanghai, 201203, PR China. Electronic address: key@sphchina.com.
  • 3 Central Research Institute, Shanghai Pharmaceuticals Holding Co., Ltd., Building 5, No. 898 Halei Road, Zhangjiang Hi-tech Park, Pudong New Area, Shanghai, 201203, PR China. Electronic address: xiagx@sphchina.com.
PMID: 32200202 DOI: 10.1016/j.ejmech.2020.112239
Abstract

CDK4/6 has been identified as an attractive therapeutic target for treatment of Cancer. For unmet clinical needs, a novel class of imidazo [1',2':1,6]pyrido [2,3-d]pyrimidin derivatives, which had distinctive triheteroaryl structure, had been discovered as CDK4/6 inhibitors. The compounds 10b and 10c, displayed the low nanomolar range activities on CDK4/6, desirable antiproliferative activities, excellent metabolic properties, and acceptable pharmacokinetic characters. In Colo-205 and U87MG xenograft models, compounds 10b and 10c also showed significant tumor growth inhibitions with controllable toxicities. All data confirmed that imidazo [1',2':1,6]pyrido [2,3-d]pyrimidin derivatives 10b and 10c could be promising drug candidates for Cancer therapy.

Keywords

Antitumor; CDK4/6 inhibitors; Cell cycle.

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