A Small-Molecule Oral Agonist of the Human Glucagon-like Peptide-1 Receptor 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.. And the article was included in Journal of Medicinal Chemistry in 2022.Recommanded Product: 1-Methyl-1H-benzo[d]imidazole-2-carbaldehyde This article mentions the following:
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 experiment, the researchers used many compounds, for example, 1-Methyl-1H-benzo[d]imidazole-2-carbaldehyde (cas: 3012-80-4Recommanded Product: 1-Methyl-1H-benzo[d]imidazole-2-carbaldehyde).
1-Methyl-1H-benzo[d]imidazole-2-carbaldehyde (cas: 3012-80-4) belongs to imidazole derivatives. The solubility of imidazoles in ethers is lower than that in alcohols and decreases with increasing chain length of the ethers . In contrast, the solubility of benzimidazoles in alcohols (C3鈥揅6) is higher than in water and generally decreases with a This ring system is present in important biological building blocks, such as histidine and the related hormone histamine.Recommanded Product: 1-Methyl-1H-benzo[d]imidazole-2-carbaldehyde
Referemce:
Imidazole – Wikipedia,
Imidazole | C3H4N2 – PubChem