US 12,226,424 B2
Target protein degradation compounds, their anti-tumor use, their intermediates and use of intermediates
Xiaobao Yang, Shanghai (CN); Biao Jiang, Shanghai (CN); Renhong Sun, Shanghai (CN); Chaowei Ren, Shanghai (CN); Ning Sun, Shanghai (CN); Ying Kong, Shanghai (CN); Yan Li, Shanghai (CN); Jinju Chen, Shanghai (CN); Qianqian Yin, Shanghai (CN); Xiaoling Song, Shanghai (CN); Quanju Zhao, Shanghai (CN); and Xing Qiu, Shanghai (CN)
Assigned to ShanghaiTech University, Shanghai (CN)
Appl. No. 17/046,690
Filed by ShanghaiTech University, Shanghai (CN)
PCT Filed Apr. 9, 2019, PCT No. PCT/CN2019/081840
§ 371(c)(1), (2) Date Oct. 9, 2020,
PCT Pub. No. WO2019/196812, PCT Pub. Date Oct. 17, 2019.
Claims priority of application No. 201810312040.8 (CN), filed on Apr. 9, 2018.
Prior Publication US 2022/0117982 A1, Apr. 21, 2022
Int. Cl. A61K 31/675 (2006.01); A61K 31/138 (2006.01); A61K 31/454 (2006.01); A61K 31/496 (2006.01); A61K 31/5025 (2006.01); A61K 31/506 (2006.01); A61K 31/519 (2006.01); A61K 31/5517 (2006.01); A61K 45/06 (2006.01); A61K 47/54 (2017.01); A61K 47/60 (2017.01); A61P 35/00 (2006.01)
CPC A61K 31/675 (2013.01) [A61K 31/138 (2013.01); A61K 31/454 (2013.01); A61K 31/496 (2013.01); A61K 31/5025 (2013.01); A61K 31/506 (2013.01); A61K 31/519 (2013.01); A61K 31/5517 (2013.01); A61K 45/06 (2013.01); A61K 47/545 (2017.08); A61K 47/60 (2017.08); A61P 35/00 (2018.01)] 17 Claims
 
1. A compound of formula (IV):

OG Complex Work Unit Chemistry
wherein,
A represents CH2 or CO,
B, X, Y, and Z represent CH,
R represents S, SO, or SO2, and
LIN is a linking group and represents W-alkylene-,
wherein -alkylene- is an alkylene group that is a linear or branched alkylene group optionally interrupted one or more times by one or more groups selected from the group consisting of O, CONH, NHCO, NH, or any combination thereof,
wherein the linear or branched alkylene group is optionally substituted with one or more substituents substituents selected from hydroxyl, amino, mercapto and halogen, or
the LIN represents: W—(CH2)n11—triazolylene—(CH2)n12—, W—(CH2)n11—triazolylene—(CH2) n12—(O(CH2)n13)m11—, W—(CH2) n11—(O(CH2) n12) m11—O—(CH2) n13—triazolylene—(CH2) n14—(O(CH2) n15) m12—O—(CH2) n16—, W—(CH2) n11-triazolylene—(CH2) n12—(O(CH2) n13) m11—O—(CH2)n14—, or W—(CH2)n11—(O (CH2)n12)m11—O—(CH2)n13—triazolylene—(CH2)n14—; and wherein n11, n12, n13, n14, n15, n16,m11, m12 each independently represent an integer of 1, 2, 3, 4, 5, 6, 7, 8, 9,10, 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20; or
the LIN represents: W—(CH2)2—O—CH2—phenylene—CH2—O—(CH2)2—, W—CH2—phenylene—CH2—, W—(CH2)3—phenylene—(CH2)3—, W—(CH2)2—O—CH2—piperazinylene—CH2—O—(CH2)2—, or W—(CH2)3—piperazinylene—(CH2)3—;
wherein W— represents N3, CHO, COOH, NH2, halogen, methanesulfonyloxy, trifluoromethanesulfonyloxy, or p-toluenesulfonyloxy;
or a salt, enantiomer, stereoisomer, or solvate thereof.