上海科技大学知识管理系统

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.

本发明公开了式(I)的抗肿瘤化合物的应用。 式(I)化合物具有抑制靶蛋白分解为ALK的作用。 式(I)化合物， 主要是， 在具有ALK-A TKI的化合物中ALK酪氨酸激酶抑制活性， LIN中不同类型的接头， VHL，蛋白酶或其它低分子量的泛素化CRBN配体(泛素连接酶结合部分)和ULM，羰基或不存在，且，ALK-A和TKI，共价结合到ULM的碱基4上的LIN共价连接由两部分组成。 本发明设计了一系列可合成的化合物，具有广泛的药理活性，具有抑制ALK蛋白水解活性的功能，可用于相关肿瘤的治疗。