US 12,071,408 B2
Multi-targeted tyrosine kinase inhibitors effective in antitumor uses
Zheng-Yun James Zhan, Shanghai (CN)
Assigned to Shanghai AB PharmaTech Ltd., Shanghai (CN)
Filed by Shanghai AB PharmaTech Ltd., Shanghai (CN)
Filed on Aug. 11, 2022, as Appl. No. 17/819,157.
Claims priority of application No. 202110924393.5 (CN), filed on Aug. 12, 2021.
Prior Publication US 2023/0123696 A1, Apr. 20, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 215/233 (2006.01); A61K 31/44 (2006.01); A61K 31/47 (2006.01); A61K 31/4709 (2006.01); A61K 31/496 (2006.01); A61K 31/506 (2006.01); A61K 31/513 (2006.01); A61K 45/06 (2006.01); A61P 11/00 (2006.01); A61P 35/00 (2006.01); A61P 35/02 (2006.01); C07D 215/48 (2006.01); C07D 401/06 (2006.01); C07D 401/12 (2006.01); C07D 405/12 (2006.01)
CPC C07D 215/233 (2013.01) [A61K 31/44 (2013.01); A61K 31/47 (2013.01); A61K 31/4709 (2013.01); A61K 31/496 (2013.01); A61K 31/506 (2013.01); A61K 31/513 (2013.01); A61K 45/06 (2013.01); A61P 11/00 (2018.01); A61P 35/00 (2018.01); A61P 35/02 (2018.01); C07D 215/48 (2013.01); C07D 401/06 (2013.01); C07D 401/12 (2013.01); C07D 405/12 (2013.01); C07B 2200/05 (2013.01)] 10 Claims
 
1. A compound represented by formula III, or a stereoisomer, tautomer, deuterate, pharmacologically acceptable salt, or hydrate thereof:

OG Complex Work Unit Chemistry
wherein:
E is independently selected from the group consisting of nitrogen (N), or CH group;
G1 is independently selected from H, deuterium (D), C1-20 alkyl group, or C1-20 alkoxy group;
G2 is independently selected from C1-20 alkoxy, or optionally deuterium-substituted C1-20 alkoxy group;
G3 is independently selected from —C(O)NH2, —C(O)ND2, or an optionally substituted C1-20 alkoxy group;
G4 and G5 are each, independently, selected from hydrogen (H), deuterium (D), halogen, —CN, C1-20 alkyl, or C1-20 alkoxy group;
R1 is independently selected from hydrogen (H), deuterium (D), C1-20 alkyl, C3-20 cycloalkyl, or —C3-20 deuterated cycloalkyl group;
R2 and R3 are each, independently, selected from hydrogen (H), deuterium (D), C1-20 alkyl, C3-20 cycloalkyl, C3-20 deuterated cycloalkyl group, or C3-20 heterocycloalkyl group; wherein R2 and R3 may be linked to each other to form C3-20 heterocyclic group with 1-3 heteroatoms;
X1, X2 and X3 are each, independently, selected from halogen, —CN, —NH2, C1-20 alkoxy group, or C1-20 alkyl amino group;
X4 is independently selected from H, deuterium (D), halogen, —NH2, C1-20 alkoxy, or C1-20 alkyl amino group.