公开(公告)号：US11639343B2

公开(公告)日：2023-05-02

申请号：US17015319

申请日：2020-09-09

Applicant: ShanghaiTech University

Inventor： Xiaobao Yang ,  Biao Jiang ,  Qianqian Yin ,  Jinju Chen ,  Quanju Zhao ,  Chaowei Ren ,  Renhong Sun ,  Ning Sun ,  Xing Qiu ,  Ying Kong ,  Yan Li ,  Linyi Liu

IPC: C07D401/14 ,  C07D417/14 ,  A61P35/02 ,  A61K45/06

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.