Takakusa, Hideo published the artcileQuantitative assessment of reactive metabolite formation using 35S-labeled glutathione, Synthetic Route of 40180-04-9, the main research area is drug metabolism reactive metabolite determination radiolabeled glutathione.
The metabolic bioactivation of a drug to a reactive metabolite (RM) and its covalent binding to cellular macromols. is believed to be involved in clin. adverse events, including idiosyncratic drug toxicities. Therefore, it is important to assess the potential of drug candidates to generate RMs and form drug-protein covalent adducts during lead optimization processes. In this study, the RM formation of some marketed drugs were quant. assessed by means of a sensitive and robust detection method that we have established using 35S-glutathione (35S-GSH) as a trapping agent. Problematic drugs well-known to generate RMs exhibited a relatively high rate of 35S-GS-adducts to RM (RM-GS) formation, which contrasted with safe drugs. For practical use in lead optimization processes, a series of new chem. entities were tested and hints on the structural modifications needed in order to minimize their RM formation were provided. Furthermore, the RM-GS formation rates of a number of compounds were compared using their in vitro covalent binding yields to liver proteins determined with 14C-labeled compounds, demonstrating that the RM-GS formation rate could be a substitute for the covalent binding yield within the same series of compounds
Drug Metabolism and Pharmacokinetics published new progress about Drug metabolism (metabolic bioactivation). 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, Synthetic Route of 40180-04-9.
Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem