Identification, Synthesis, and Characterization of Potential Oxidative Impurities of Venetoclax: Application of Meisenheimer Rearrangement.

ABSTRACT: Venetoclax is a potent BCL-2 inhibitor that is used for the treatment of several blood cancers. During the oxidative stress degradation of venetoclax, we observed the formation of two potential impurities at levels of about 8-10%, which have similar molecular weights. The two impurities were isolated and identified as 4-(3-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(((3-nitro-4-(((tetrahydro-2H-pyran-4-yl)methyl)amino)phenyl)sulfonyl)carbamoyl)phenyl)-1-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazine 1-oxide (venetoclax N-oxide, VNO) and 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methoxy)piperazin-1-yl)-N-((3-nitro-4-(((tetrahydro-2H

SUBMITTER: Vaddamanu G 

PROVIDER: S-EPMC10586452 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature