Target protein degradation compounds, their anti-tumor use, their intermediates and use of intermediates

US12226424B2 · kind B2 · utility

Assignee

• SHANGHAITECH UNIVERSITY · CN

Inventors

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

Key dates

• Filing date: Apr 9, 2019
• Grant date: Feb 18, 2025
• Expiry date: Oct 16, 2040

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D495/14
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The present disclosure relates to compounds of formula (I) and their anti-tumor uses, and their intermediates of formula (III), intermediates of formula (IV), and uses of the intermediates. The compound of formula (I) has a degrading effect on a specific target protein, which is mainly composed of three parts. The first part is a small molecule compound (SMBP, Small Molecules Binding Protein) that can bind to a protein, the second part LIN is a linker, and the three-part ULM is a ubiquitin ligand (ULM, Ubiquitin Ligase Binding Moiety), wherein SMBP is covalently bound to LIN, and LIN is covalently bound to ULM. A series of compounds designed and synthesized in the present disclosure have a wide range of pharmacological activities, including the functions of degrading specific proteins and/or inhibiting activities of specific proteins, and thus can be used in related tumor treatments.