US 12,448,372 B2
Class of triaromatic compounds targeting bifunctional phosphorylation site of STAT3 and applications thereof
Yihua Chen, Shanghai (CN); Wenbo Zhou, Shanghai (CN); Huang Chen, Shanghai (CN); Zhengfang Yi, Shanghai (CN); Xiufeng Pang, Shanghai (CN); and Mingyao Liu, Shanghai (CN)
Assigned to SHANGHAI YUYAO BIOTECH LTD., Shanghai (CN)
Appl. No. 17/631,755
Filed by SHANGHAI YUYAO BIOTECH LTD., Shanghai (CN)
PCT Filed Jul. 16, 2020, PCT No. PCT/CN2020/102461
§ 371(c)(1), (2) Date Jan. 31, 2022,
PCT Pub. No. WO2021/017880, PCT Pub. Date Feb. 4, 2021.
Claims priority of application No. 201910698892.X (CN), filed on Jul. 31, 2019.
Prior Publication US 2022/0274972 A1, Sep. 1, 2022
Int. Cl. A61P 1/04 (2006.01); A61K 31/497 (2006.01); A61K 45/06 (2006.01); A61P 11/00 (2006.01); A61P 13/12 (2006.01); A61P 17/06 (2006.01); A61P 19/02 (2006.01); A61P 29/00 (2006.01); A61P 35/00 (2006.01); A61P 37/02 (2006.01); C07D 413/14 (2006.01)
CPC C07D 413/14 (2013.01) [A61K 45/06 (2013.01); A61P 35/00 (2018.01)] 15 Claims
OG exemplary drawing
 
1. A triaromatic compound targeting bifunctional phosphorylation site of STAT3, or a pharmaceutically acceptable salt thereof, wherein the triaromatic compound is a compound of formula (III):

OG Complex Work Unit Chemistry
wherein
W, Q, E, T, U, M and K are each independently selected from the group consisting of CH, CH═CH, CH═NH, NH, N, O and S;
G and L are each independently selected from the group consisting of NH, NR2, O, and S;
R1 is selected from the group consisting of hydrogen, hydroxyl, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl, 3-8 membered heterocyclyl, C5-10aryl, 5-10 membered heteroaryl, C1-6alkoxy, C3-8cycloalkoxy, —S(O)pR4, —C(O)R4, —C(O)OR4, —NR5R6, and —C(O)NR6; wherein the 5-10 membered heteroaryl is substituted with one or more substituents selected from the group consisting of halogen, hydroxyl, cyano, nitro, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl, 3-8 membered heterocyclyl, C5-10aryl, 5-10 membered heteroaryl, C1-6alkoxy, C3-8cycloalkoxy, —S(O)pR4, —C(O)R4, —C(O)OR4, —NR5R6, and —C(O)NR6; wherein R4, R5, R6 are each independently hydrogen, or C1-4alkyl, p is 0, 1, or 2; or R1 is selected from the group consisting of —F, —CF3, Cl, Br, and —OCF3;
R2 is selected from the group consisting of hydrogen, hydroxyl, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl, 3-8 membered heterocyclyl, C5-10aryl, 5-10 membered heteroaryl, C1-6alkoxy, C3-8cycloalkoxy, —S(O)pR4, —C(O)R4, —C(O)OR4, —NR5R6, and —C(O)NR6; wherein the 5-10 membered heteroaryl is substituted with one or more substituents selected from the group consisting of halogen, hydroxyl, cyano, nitro, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl, 3-8 membered heterocyclyl, C5-10aryl, 5-10 membered heteroaryl, C1-6alkoxy, C3-8cycloalkoxy, —S(O)pR4, —C(O)R4, —C(O)OR4, —NR5R6, and —C(O)NR6; wherein R4, R5, and R6 are each independently selected from the group consisting of hydrogen and C1-4alkyl, p is 0, 1, or 2; and
R3 is selected from the group consisting of hydrogen, hydroxyl, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl, 3-8 membered heterocyclyl, C5-10aryl, 5-10 membered heteroaryl, C1-6alkoxy, C3-8cycloalkoxy, —S(O)pR4, —C(O)R4, —C(O)OR4, —NR5R6, and —C(O)NR6; wherein the 5-10 membered heteroaryl is substituted with one or more substituents selected from the group consisting of halogen, hydroxyl, cyano, nitro, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl, 3-8 membered heterocyclyl, C5-10aryl, 5-10 membered heteroaryl, C1-6alkoxy, C3-8cycloalkoxy, —S(O)pR4, —C(O)R4, —C(O)OR4, —NR5R6, and —C(O)NR6; wherein R4, R5, and R6 are each independently selected from the group consisting of hydrogen and C1-4alkyl, p is 0, 1, or 2; or R3 is selected from the group consisting of

OG Complex Work Unit Chemistry