Application of 301673-14-3In 2022 ,《A Small-Molecule Oral Agonist of the Human Glucagon-like Peptide-1 Receptor》 was published in Journal of Medicinal Chemistry. The article was written by Griffith, David A.; Edmonds, David J.; Fortin, Jean-Philippe; Kalgutkar, Amit S.; Kuzmiski, J. Brent; Loria, Paula M.; Saxena, Aditi R.; Bagley, Scott W.; Buckeridge, Clare; Curto, John M.; Derksen, David R.; Dias, Joao M.; Griffor, Matthew C.; Han, Seungil; Jackson, V. Margaret; Landis, Margaret S.; Lettiere, Daniel; Limberakis, Chris; Liu, Yuhang; Mathiowetz, Alan M.; Patel, Jayesh C.; Piotrowski, David W.; Price, David A.; Ruggeri, Roger B.; Tess, David A.. The article contains the following contents:
Peptide agonists of the glucagon-like peptide-1 receptor (GLP-1R) have revolutionized diabetes therapy, but their use has been limited because they require injection. Herein, we describe the discovery of the orally bioavailable, small-mol., GLP-1R agonist PF-06882961 (danuglipron). A sensitized high-throughput screen was used to identify 5-fluoropyrimidine-based GLP-1R agonists that were optimized to promote endogenous GLP-1R signaling with nanomolar potency. Incorporation of a carboxylic acid moiety provided considerable GLP-1R potency gains with improved off-target pharmacol. and reduced metabolic clearance, ultimately resulting in the identification of danuglipron. Danuglipron increased insulin levels in primates but not rodents, which was explained by receptor mutagenesis studies and a cryogenic electron microscope structure that revealed a binding pocket requiring a primate-specific tryptophan 33 residue. Oral administration of danuglipron to healthy humans produced dose-proportional increases in systemic exposure (NCT03309241). This opens an opportunity for oral small-mol. therapies that target the well-validated GLP-1R for metabolic health. In the part of experimental materials, we found many familiar compounds, such as tert-Butyl 4-iodopiperidine-1-carboxylate(cas: 301673-14-3Application of 301673-14-3)
tert-Butyl 4-iodopiperidine-1-carboxylate(cas: 301673-14-3) is one of organic iodides. The carbon-iodine bond is weaker than other carbon-halogen bonds due to the poor electronegative nature of the iodine atom. In general, organic iodides are light-sensitive and turn yellow during storage, owing to the formation of iodine. Organic iodides can be alkyl, alkenyl, or alkynyl, and all of them are very reactive toward with many kinds of nucleophiles.Application of 301673-14-3
Referemce:
Iodide – Wikipedia,
Iodide – an overview | ScienceDirect Topics – ScienceDirect.com