Zhang, Chenghong published the artcileStrategies to Mitigate the Bioactivation of Aryl Amines, Category: piperazines, the publication is Chemical Research in Toxicology (2020), 33(7), 1950-1959, database is CAplus and MEDLINE.
The bioactivation of xenobiotics to yield reactive metabolites can lead to tolerability and toxicity concerns within a drug discovery program. Development of strategies for mitigating the metabolic liability of commonly encountered toxicophores, such as anilines, relies on an understanding of the relative tendency of these functionalities to undergo bioactivation. In this report, we present the first systematic study of the structure-activity relationships of the bioactivation of aryl amine fragments (mol. weight < 250 Da) using a glutathione (GSH) trapping assay in the presence of human liver microsomes and the reduced form of NADP. This study demonstrates that conversion of anilines to nitrogen-containing heteroarylamines results in a lower abundance of GSH conjugates in the order Ph > pyrimidine ≈ pyridine > pyridazine. Introduction of electron-withdrawing functionality on the aromatic ring had a less pronounced effect on the extent of GSH conjugation. Examination of more drug-like compounds sourced from inhouse drug discovery programs revealed similar trends in bioactivation between matched pairs containing (hetero)aryl amines. This study provides medicinal chemists with insights and qual. guidance for the minimization of risks related to aryl amine metabolism
Chemical Research in Toxicology published new progress about 55403-35-5. 55403-35-5 belongs to piperazines, auxiliary class Pyridine,Piperazine,Amine, name is 6-(4-Methylpiperazin-1-yl)pyridin-3-amine, and the molecular formula is C20H32B2O4, Category: piperazines.
Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics