In 2017,Wagman, Allan S.; Boyce, Rustum S.; Brown, Sean P.; Fang, Eric; Goff, Dane; Jansen, Johanna M.; Le, Vincent P.; Levine, Barry H.; Ng, Simon C.; Ni, Zhi-Jie; Nuss, John M.; Pfister, Keith B.; Ramurthy, Savithri; Renhowe, Paul A.; Ring, David B.; Shu, Wei; Subramanian, Sharadha; Zhou, Xiaohui A.; Shafer, Cynthia M.; Harrison, Stephen D.; Johnson, Kirk W.; Bussiere, Dirksen E. published 《Synthesis, Binding Mode, and Antihyperglycemic Activity of Potent and Selective (5-Imidazol-2-yl-4-phenylpyrimidin-2-yl)[2-(2-pyridylamino)ethyl]amine Inhibitors of Glycogen Synthase Kinase 3》.Journal of Medicinal Chemistry published the findings.Reference of 2-(2-Hydroxyethyl)pyridine The information in the text is summarized as follows:
In an effort to identify new antidiabetic agents, we have discovered a novel family of (5-imidazol-2-yl-4-phenylpyrimidin-2-yl)[2-(2-pyridylamino)ethyl]amine analogs which are inhibitors of human glycogen synthase kinase 3 (GSK3). We developed efficient synthetic routes to explore a wide variety of substitution patterns and convergently access a diverse array of analogs. Compound I (CHIR-911, CT-99021, or CHIR-73911) emerged from an exploration of heterocycles at the C-5 position, Ph groups at C-4, and a variety of differently substituted linker and aminopyridine moieties attached at the C-2 position. These compounds exhibited GSK3 IC50s in the low nanomolar range and excellent selectivity. They activate glycogen synthase in insulin receptor-expressing CHO-IR cells and primary rat hepatocytes. Evaluation of lead compounds I and II (CHIR-611 or CT-98014) in rodent models of type 2 diabetes revealed that single oral doses lowered hyperglycemia within 60 min, enhanced insulin-stimulated glucose transport, and improved glucose disposal without increasing insulin levels. The results came from multiple reactions, including the reaction of 2-(2-Hydroxyethyl)pyridine(cas: 103-74-2Reference of 2-(2-Hydroxyethyl)pyridine)
2-(2-Hydroxyethyl)pyridine(cas: 103-74-2) belongs to pyridine. Pyridines form stable salts with strong acids. Pyridine itself is often used to neutralize acid formed in a reaction and as a basic solvent. Reference of 2-(2-Hydroxyethyl)pyridine