Application of a micropatterned cocultured hepatocyte system to predict preclinical and human-specific drug metabolism was written by Ballard, T. Eric;Wang, Shuai;Cox, Loretta M.;Moen, Mark A.;Krzyzewski, Stacy;Ukairo, Okechukwu;Obach, R. Scott. And the article was included in Drug Metabolism & Disposition in 2016.Synthetic Route of C6H6N4 This article mentions the following:
Laboratory animal models are the industry standard for preclin. risk assessment of drug candidates. Thus, it is important that these species possess profiles of drug metabolites that are similar to those anticipated in human, since metabolites also could be responsible for biol. activities or unanticipated toxicity. Under most circumstances, preclin. species reflect human in vivo metabolites well; however, there have been several notable exceptions, and understanding and predicting these exceptions with an in vitro system would be very useful. Human micropatterned cocultured (MPCC) hepatocytes have been shown to recapitulate human in vivo qual. metabolic profiles, but the same demonstration has not been performed yet for laboratory animal species. In this study, we investigated several compounds that are known to produce human-unique metabolites through CYP2C9, UGT1A4, aldehyde oxidase (AO), or N-acetyltransferase that were poorly covered or not detected at all in the selected preclin. species. To perform our investigation we used 24-well MPCC hepatocyte plates having three individual human donors and a single donor each of monkey, dog, and rat to study drug metabolism at four time points per species. Through the use of the multispecies MPCC hepatocyte system, the metabolite profiles of the selected compounds in human donors effectively captured the qual. in vivo metabolite profile with respect to the human metabolite of interest. Human-unique metabolites that were not detected in vivo in certain preclin. species (normally dog and rat) were also not generated in the corresponding species in vitro, confirming that the MPCC hepatocytes can provide an assessment of preclin. species metabolism From these results, we conclude that multispecies MPCC hepatocyte plates could be used as an effective in vitro tool for preclin. understanding of species metabolism relative to humans and aid in the choice of appropriate preclin. models. In the experiment, the researchers used many compounds, for example, 1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6Synthetic Route of C6H6N4).
1H-Benzo[d][1,2,3]triazol-1-amine (cas: 1614-12-6) belongs to triazole derivatives. The triazole ring is a relatively stable functional group, and the triazole bond can be used for a variety of applications, such as replacing the phosphate backbone of DNA. The presence of the three nitrogen atoms in triazole structures afforded opportunities for a plethora of structural modification with the generation of novel therapeutically potential agents, which is different from other heterocyclic compounds.Synthetic Route of C6H6N4
Referemce:
1,2,3-Triazole – Wikipedia,
Triazoles – an overview | ScienceDirect Topics