Formula: C7H6BrNO2In 2016 ,《Discovery of 2-((R)-4-(2-Fluoro-4-(methylsulfonyl)phenyl)-2-methylpiperazin-1-yl)-N-((1R,2s,3S,5S,7S)-5-hydroxyadamantan-2-yl)pyrimidine-4-carboxamide (SKI2852): A Highly Potent, Selective, and Orally Bioavailable Inhibitor of 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD1)》 was published in Journal of Medicinal Chemistry. The article was written by Ryu, Je Ho; Lee, Jung A.; Kim, Shinae; Shin, Young Ah; Yang, Jewon; Han, Hye Young; Son, Hyun Joo; Kim, Yong Hyuk; Sa, Joon Ho; Kim, Jae-Sun; Lee, Jungeun; Lee, Jeeyeon; Park, Hyeung-geun. The article contains the following contents:
A series of picolinamide- and pyrimidine-4-carboxamide-based inhibitors of 11β-hydroxysteroid dehydrogenase type 1 was synthesized and evaluated to optimize the lead compound The combination of the replacement of a pyridine ring of the lead compd with a pyrimidine ring and the introduction of an addnl. fluorine substituent at the 2-position of the Ph ring resulted in the discovery of a potent, selective, and orally bioavailable inhibitor, SKI2852, which demonstrated no CYP and PXR liabilities, excellent PK profiles across species, and highly potent and sustainable PD activity. Repeated oral administration of SKI2852 significantly reduced blood glucose and HbA1c levels and improved the lipid profiles in ob/ob mice. Moreover, the HbA1c-lowering effect of metformin was synergistically enhanced in combination with SKI2852. In the part of experimental materials, we found many familiar compounds, such as Methyl 5-bromopicolinate(cas: 29682-15-3Formula: C7H6BrNO2)
Methyl 5-bromopicolinate(cas: 29682-15-3) belongs to pyridine. Pyridines, quinolines, and isoquinolines have found a function in almost all aspects of organic chemistry. Pyridine has found use as a solvent, base, ligand, functional group, and molecular scaffold. As structural elements, these moieties are potent electron-deficient groups, metal-directing functionalities, fluorophores, and medicinally important pharmacophores. Formula: C7H6BrNO2