Compounds targeting and degrading BCR-ABL protein and its antitumor application

US11639343B2 · kind B2 · utility

Assignee

• SHANGHAITECH UNIVERSITY · CN

Inventors

• Xiaobao Yang · New York, US
• Biao Jiang · Shanghai, CN
• Qianqian Yin · Shanghai, CN
• Jinju Chen · Shanghai, CN
• Quanju Zhao · Shanghai, CN
• Chaowei Ren · Zhuqiao, CN
• Renhong Sun · Shanghai, CN
• Ning Sun · Fremont, US
• Xing Qiu · Shanghai, CN
• Ying Kong · Shanghai, CN
• Yan Li · Tallahassee, US
• Linyi LIU · Shanghai, CN

Key dates

• Filing date: Sep 9, 2020
• Grant date: May 2, 2023
• Expiry date: Sep 9, 2040

Classification

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

Abstract

The present disclosure provides a compound of formula (I) targeting and degrading BCR-ABL protein and its use in the field of antitumor. The compound of formula (I) shows degradation and inhibitory effects on BCR-ABL target protein, which is mainly comprised of four moieties, wherein the first moiety (BCR-ABL-TKIs) is compound moiety with BCR-ABL tyrosine kinase inhibited activity; the second moiety (the LIN) is link units; the third moiety (the ULM) is a small molecule ligand for VHL or CRBN proteases with ubiquitination; and the four moiety (the group A) is carbonyl group that covalently binds to BCR-ABL-TKIs and LIN, and the LIN is further covalently bonded to ULM. A series of compounds designed and synthesized by the present disclosure shows extensive pharmacological effective, which function to degrade BCR-ABL protein and inhibit BCR-ABL effective, and can be utilized for treating relevant tumor.