US 12,291,531 B2
Matrine α-ketoamine compounds, preparation method therefor and use thereof
Weibin Song, Shanghai (CN); and Yanhui Liu, Shanghai (CN)
Assigned to SHANGHAI XINGYE PHARMACEUTICAL TECHNOLOGY CO., LTD, Shanghai (CN)
Appl. No. 17/267,961
Filed by SHANGHAI XINGYE PHARMACEUTICAL TECHNOLOGY CO., LTD, Shanghai (CN)
PCT Filed Aug. 14, 2019, PCT No. PCT/CN2019/100674
§ 371(c)(1), (2) Date Feb. 11, 2021,
PCT Pub. No. WO2020/035010, PCT Pub. Date Feb. 20, 2020.
Claims priority of application No. 201810918861.6 (CN), filed on Aug. 14, 2018.
Prior Publication US 2021/0221812 A1, Jul. 22, 2021
Int. Cl. C07D 471/22 (2006.01); A61P 35/00 (2006.01)
CPC C07D 471/22 (2013.01) [A61P 35/00 (2018.01)] 12 Claims
 
1. A matrine α-ketoamine derivative having a structure of general formula (I), a pharmaceutically acceptable salt, a stereoisomer, or an isotopic compound thereof;

OG Complex Work Unit Chemistry
wherein each of R1, R2, R3 and R4 is independently selected from H, D, halogen, hydroxyl, amino, nitro, cyano, carboxyl, mercapto, (C0-C8) alkoxyformyl C1-C8 alkoxyl, C1-C8 alkanesulfonyl, (C1-C8) alkanesulfonamido, (C0-C8) alkylaminosulfonyl, (C1-C8) alkyl, halo (C1-C8) alkyl, halo (C1-C8) alkoxyl, (C0-C8) alkylethynyl, (C1-C8) alkoxyl, (C1-C8) alkylacyloxy, (C1-C8) alkoxyl (C1-C8) alkoxyl, (C1-C8) alkoxyl (C1-C8) alkyl, (C1-C8) alkylamino, (C0-C8) alkylamino (C1-C8) alkyl, aryl, aryl (C1-C8) alkylamino (C1-C8) alkyl, amidino, guanidino, arylsulfonamido, arylaminosulfonyl, benzoyl, aryl (C1-C8) alkylamino, aryl (C1-C8) alkylamido, (C1-C8) alkoxyformyl, (C1-C8) alkylamido, (C0-C8) alkylamino selenyl, (C0-C8) alkylamino formamido, (C0-C8) alkylamino formyl, (C1-C8) alkylaminoformyloxyl, arylaminoformamido, arylaminoformyl, aryl (C0-C8) alkylaminoformyl, arylaminoformyloxyl, or absent; wherein, the aryl groups of R1, R2, R3 and R4 described are phenyl or are phenyl which independently substituted with 1-4 halogen, hydroxy, nitro, cyano, amino, trifluoromethyl, carboxyl, (C1-C8) alkanesulfonamido, (C1-C8) alkyl, halo (C1-C8) alkoxyl, (C1-C8) alkoxyl groups;
Y is O or not exist;
Z1 is selected from SO2, C═O, C═NR5, COCO, CH2CO, CH(CH3)CO, CH2, CH(CH3)2, CH2CH(CH3)2, or H;
Z2 is selected from SO2, C═O, C═NR5, COCO, CH2CO, CH(CH3)CO, CH2, CH(CH3)2, or CH2CH(CH3)2;
wherein, R5 is selected from H, (C1-C8) alkoxyl;
W1 and/or W2 are independently selected from N or C; wherein, when W1 and/or W2 is N, R1 and R3 are not exist;
Where bonds represented by “-----” is a chemical bond or not exist.