ALK protein degradation agent and anti-tumor application thereof

US11771709B2 · kind B2 · utility

Assignee

• SHANGHAITECH UNIVERSITY · CN

Inventors

• Xiaobao Yang · New York, US
• Biao Jiang · Shanghai, CN
• Xiaoling Song · Woodinville, US
• Haifan Lin · Durham, US
• Ning Sun · Fremont, US
• Jinju Chen · Shanghai, CN
• Xing Qiu · Shanghai, CN
• Chaowei Ren · Zhuqiao, CN
• Ying Kong · Shanghai, CN

Key dates

• Filing date: Jun 15, 2020
• Grant date: Oct 3, 2023
• Expiry date: Jun 15, 2040

Classification

• Technology area (CPC A): Human Necessities
• CPC primary: A61K45/06
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

A compound of formula (I) and its antitumor application are disclosed. The compounds of formula (I) have degradation and inhibitory effects on ALK target proteins. They are mainly composed of four parts: the first part, ALK-TKI, being compounds with ALK tyrosine kinase inhibitory activity; the second part, LIN, being different kinds of linker (Linker); the third part, the ULM, being a small molecule ligand (ULM, ubiquitin ligase binding moiety) with ubiquitination of VHL, CRBN or other proteases; and the fourth part, the group A, being a carbonyl group or absent, which covalently bond ALK-TKI to LIN, wherein LIN and ULM are covalently bonded. A series of compounds designed and synthesized by the present disclosure have wide pharmacological activities, have functions of degrading ALK protein and inhibiting ALK activity, and can be used for related tumor treatment.