Pyrimido[5,4-B]indolizine or pyrimido[5,4-B]pyrrolizine compound, preparation method and use thereof

US10829491B2 · kind B2 · utility

Assignee

• SHANGHAI INSTITUTE OF MATERIA MEDICA, CHINESE ACAD · CN

Inventors

• Ao Zhang · Beijing, CN
• Jian Ding · Shanghai, CN
• Hua Xie · Shanghai, CN
• Zilan Song · Shanghai, CN
• Yu-Yi Xue · Houston, US
• Linjiang Tong · Shanghai, CN
• Meiyu Geng · Shanghai, CN

Key dates

• Filing date: Nov 24, 2017
• Grant date: Nov 10, 2020
• Expiry date: Nov 24, 2037

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D487/14
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The present disclosure relates to a Pyrimido[5,4-b]indolizine or pyrimido[5,4-b]pyrrolizine compound, preparation method thereof and use thereof. The compounds of the present invention have good inhibitory activities against BTK at the molecular and cellular levels. Importantly, the compounds of the present invention have low activity against Ramos cells of normal human B lymphoma cells, and have high activity against BTK-sensitive human diffuse large B lymphoma TMD8 cells, indicating that these type of compounds with novel structural are highly selective, off-target phenomenon and corresponding side effects are low. Thus it is a selective inhibitor of BTK with development potential.