Substituted pyrimidines as cyclin-dependent kinase inhibitors

US10662186B2 · kind B2 · utility

Assignee

• Shanghai Pharmaceuticals Holding Co., Ltd. · CN

Inventors

• Guangxin Xia · Shanghai, CN
• Qian Wang · Santa Clara, US
• Chen Shi · Beijing, CN
• Xiong Zhai · Shanghai, CN
• Hui Ge · Zhejiang, CN
• Xuemei LIAO · Shanghai, CN
• Yu MAO · Shanghai, CN
• Zhixiong Xiang · Shanghai, CN
• Yanan HAN · Shanghai, CN
• Guoyong HUO · Shanghai, CN
• Yanjun Liu · Shanghai, CN

Key dates

• Filing date: Dec 30, 2016
• Grant date: May 26, 2020
• Expiry date: Dec 30, 2036

Classification

• Technology area (CPC Y): Emerging Cross-Sectional Technologies
• CPC primary: Y02P20/55
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

The present invention discloses a nitrogen-containing fused heterocyclic compound, as well as a preparation method, intermediate, composition and application thereof. The nitrogen-containing fused heterocyclic compound of the present invention as represented by formula (I), as well as the pharmaceutically acceptable salt, enantiomer, diastereomer, tautomer, solvate, metabolite or drug precursor thereof, exhibit a high selectivity and a high inhibitory activity with respect to CDK4 and CDK6 at a molecular level, an excellent inhibitory activity with respect to breast cancer cells at a cellular level, and significant inhibition of tumor cell proliferation associated with cyclin-dependent kinase activity at an animal level. The invention also exhibits a good stability with respect to human or mouse liver microsomes without significant inhibition of metabolic enzymes, good in vivo absorption in mice and rats, a high bioavailability and good druggability.