Barilli, Alessio published the artcileFrom 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, Application of 5-Chlorothiazole-2-ethanone, the publication is Journal of Medicinal Chemistry (2021), 64(9), 5931-5955, database is CAplus and MEDLINE.
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.
Journal of Medicinal Chemistry published new progress about 774230-95-4. 774230-95-4 belongs to thiazole, auxiliary class Thiazole,Chloride,Aldehyde, name is 5-Chlorothiazole-2-ethanone, and the molecular formula is C5H4ClNOS, Application of 5-Chlorothiazole-2-ethanone.
Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica