From High-Throughput Screening to Target Validation: Benzo[d]isothiazoles as Potent and Selective Agonists of Human Transient Receptor Potential Cation Channel Subfamily M Member 5 Possessing In Vivo Gastrointestinal Prokinetic Activity in Rodents was written by Barilli, Alessio;Aldegheri, Laura;Bianchi, Federica;Brault, Laurent;Brodbeck, Daniela;Castelletti, Laura;Feriani, Aldo;Lingard, Iain;Myers, Richard;Nola, Selena;Piccoli, Laura;Pompilio, Daniela;Raveglia, Luca F.;Salvagno, Cristian;Tassini, Sabrina;Virginio, Caterina;Sabat, Mark. And the article was included in Journal of Medicinal Chemistry in 2021.Application of 76-83-5 This article mentions the following:
Transient receptor potential cation channel subfamily M member 5 (TRPM5) is a nonselective monovalent cation channel activated by intracellular Ca2+ increase. Within the gastrointestinal system, TRPM5 is expressed in the stoma, small intestine, and colon. In the search for a selective agonist of TRPM5 possessing in vivo gastrointestinal prokinetic activity, a high-throughput screening was performed and compound 1 was identified as a promising hit. Hit validation and hit to lead activities led to the discovery of a series of benzo[d]isothiazole derivatives Among these, compounds 61 and 64 showed nanomolar activity and excellent selectivity (>100-fold) vs. related cation channels. The in vivo drug metabolism and pharmacokinetic profile of compound 64 was found to be ideal for a compound acting locally at the intestinal level, with minimal absorption into systemic circulation. Compound 64 was tested in vivo in a mouse motility assay at 100 mg/kg, and demonstrated increased prokinetic activity. In the experiment, the researchers used many compounds, for example, (Chloromethanetriyl)tribenzene (cas: 76-83-5Application of 76-83-5).
(Chloromethanetriyl)tribenzene (cas: 76-83-5) belongs to organic chlorides. Chlorinated organic compounds are found in nearly every class of biomolecules and natural products including alkaloids, terpenes, amino acids, flavonoids, steroids, and fatty acids. Alkanes and aryl alkanes may be chlorinated under free radical conditions, with UV light. However, the extent of chlorination is difficult to control.Application of 76-83-5
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics