US 12,331,058 B2
SHP2 and CDK4/6 dual-target inhibitory compound and pharmaceutical composition containing the same
Xiaoxing Wu, Jiangsu (CN); Xiaoyu Chen, Jiangsu (CN); Wenqiang Li, Jiangsu (CN); Chengxia Shu, Jiangsu (CN); Guangmei Luo, Jiangsu (CN); and Kexin Yang, Jiangsu (CN)
Assigned to CHINA PHARMACEUTICAL UNIVERSITY, Jiangsu (CN)
Appl. No. 18/705,978
Filed by CHINA PHARMACEUTICAL UNIVERSITY, Jiangsu (CN)
PCT Filed Jul. 21, 2022, PCT No. PCT/CN2022/106982
§ 371(c)(1), (2) Date Apr. 29, 2024,
PCT Pub. No. WO2023/071314, PCT Pub. Date May 4, 2023.
Claims priority of application No. 202111272628.3 (CN), filed on Oct. 29, 2021.
Prior Publication US 2025/0026756 A1, Jan. 23, 2025
Int. Cl. C07D 487/04 (2006.01); A61K 31/506 (2006.01); A61K 31/519 (2006.01); A61K 31/55 (2006.01); A61P 35/00 (2006.01); C07D 401/14 (2006.01); C07D 491/107 (2006.01); C07D 519/00 (2006.01)
CPC C07D 487/04 (2013.01) [A61K 31/506 (2013.01); A61K 31/519 (2013.01); A61K 31/55 (2013.01); A61P 35/00 (2018.01); C07D 401/14 (2013.01); C07D 491/107 (2013.01); C07D 519/00 (2013.01)] 6 Claims
 
1. A compound as shown in General Formula III, and pharmaceutically acceptable salts, enantiomers, diastereomers, tautomers, solvates, polymorphs, or prodrugs thereof

OG Complex Work Unit Chemistry
wherein,
ring A is selected from

OG Complex Work Unit Chemistry
ring B is selected from aromatic ring, heteroaromatic ring, carbocyclic ring, heterocyclic ring; wherein the aromatic ring, the heteroaromatic ring, the carbocyclic ring, the heterocyclic ring optionally contain heteroatoms selected from N, O and S(O)m; where m is selected from 0, 1 and 2; where the aromatic ring, the heteroaromatic ring, the carbocyclic ring, the heterocyclic ring are optionally substituted with one or a plurality of substituents;
L2 is a chemical bond, NRa, a carbon chain with C1-C2, O, S(O)m, where m is selected from 0, 1 and 2;
R1, R2 are hydrogen, deuterium atom, halogen, amino, hydroxy, cyano, nitro, carboxyl, sulfonic acid group and C1-C6 alkyl, C3-C6 cycloalkyl, C6-C10 aryl, C6-C10 heteroaryl, respectively; wherein the amino, the hydroxy, the aryl, the heteroaryl, the cycloalkyl are optionally substituted with one or a plurality of substituents;
alternatively, a 3 membered to 12 membered mono-heterocyclic ring or polycyclic heterocyclic ring is formed by R1 and R2 together with the carbon atoms attached to both R1 and R2, wherein the mono-heterocyclic ring or the polycyclic heterocyclic ring optionally contains heteroatoms selected from N, O and S(O)m; wherein m is selected from 0, 1 and 2; where the mono-heterocyclic ring or the polycyclic heterocyclic ring is unsubstituted or substituted with one or a plurality of substituents;
alternatively,

OG Complex Work Unit Chemistry
is formed by R1 and R2 together with the carbon atoms attached to both R1 and R2,
wherein W is absent or selected from CR6R7, O, NRb, S(O)m, where m is selected from 0, 1 and 2;
ring C is absent or selected from C3-C7 membered monocyclic ring, or C5-C12 membered polycyclic ring;
Ra, Rb are independently selected from hydrogen, deuterium atoms, C1-C6 alkyl, C3-C6 cycloalkyl, C6-C10 aryl, C6-C10 heteroaryl;
R4, R5, R6, R7 are independently selected from hydrogen, deuterium atom, halogen, amino, hydroxy, cyano, nitro, carboxyl, sulfonic acid group, C1-C6 alkyl, C3-C6 cycloalkyl, C6-C10 aryl, C6-C10 heteroaryl; where the amino, the hydroxy, the aryl, the heteroaryl, the cycloalkyl are optionally substituted with one or a plurality of substituents;
alternatively, CO, C═NH, C3-C12 membered heterocyclic ring or C3-C8 cycloalkyl is formed by R4 and R5 together with the carbon atoms attached to both R4 and R5.