Darout, Etzer; Robinson, Ralph P.; McClure, Kim F.; Corbett, Matthew; Li, Bryan; Shavnya, Andrei; Andrews, Melissa P.; Jones, Christopher S.; Li, Qifang; Minich, Martha L.; Mascitti, Vincent; Guimaraes, Cristiano R. W.; Munchhof, Michael J.; Bahnck, Kevin B.; Cai, Cuiman; Price, David A.; Liras, Spiros; Bonin, Paul D.; Cornelius, Peter; Wang, Ruduan; Bagdasarian, Victoria; Sobota, Colleen P.; Hornby, Sam; Masterson, Victoria M.; Joseph, Reena M.; Kalgutkar, Amit S.; Chen, Yue published the artcile< Design and Synthesis of Diazatricyclodecane Agonists of the G-Protein-Coupled Receptor 119>, Safety of 4,6-Dichloro-5-methoxypyrimidine, the main research area is diazatricyclodecane derivative preparation agonist G protein coupled receptor 119; Hofmann Loeffler Freytag reaction formation bicyclic framework; ligand lipophilic efficiency diazatricyclodecane.
A series of GPR119 agonists based on a 2,6-diazatricyclo[3.3.1.1∼3,7∼]decane ring system is described. Also provided is a detailed account of the development of a multigram scale synthesis of the diazatricyclic ring system, which was achieved using a Hofmann-Loeffler-Freytag reaction as the key step. The basis for the use of this complex framework lies in an attempt to constrain one end of the mol. in the “”agonist conformation”” as was previously described for 3-oxa-7-aza-bicyclo[3.3.1]nonanes. Optimization of carbamate analogs of the diazatricyclic compounds led to the identification of I as a potent agonist of the GPR119 receptor with low unbound human liver microsomal clearance. The use of an agonist response weighted ligand lipophilic efficiency (LLE) termed AgLLE is discussed along with the issues of applying efficiency measures to agonist programs. Ultimately, solubility limited absorption and poor exposure reduced further interest in these mols.
Journal of Medicinal Chemistry published new progress about Crystal structure. 5018-38-2 belongs to class pyrimidines, and the molecular formula is C5H4Cl2N2O, Safety of 4,6-Dichloro-5-methoxypyrimidine.
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia