Duplantier, Allen J.; Becker, Stacey L.; Bohanon, Michael J.; Borzilleri, Kris A.; Chrunyk, Boris A.; Downs, James T.; Hu, Lain-Yen; El-Kattan, Ayman; James, Larry C.; Liu, Shenping; Lu, Jiemin; Maklad, Noha; Mansour, Mahmoud N.; Mente, Scot; Piotrowski, Mary A.; Sakya, Subas M.; Sheehan, Susan; Steyn, Stefanus J.; Strick, Christine A.; Williams, Victoria A.; Zhang, Lei published the artcile< Discovery, SAR, and Pharmacokinetics of a Novel 3-Hydroxyquinolin-2(1H)-one Series of Potent D-Amino Acid Oxidase (DAAO) Inhibitors>, COA of Formula: C6H6N2O, the main research area is amino acid oxidase inhibitor hydroxyquinolinone preparation SAR.
3-Hydroxyquinolin-2(1H)-one (2) was discovered by high throughput screening in a functional assay to be a potent inhibitor of human DAAO, and its binding affinity was confirmed in a Biacore assay. Cocrystn. of 2 with the human DAAO enzyme defined the binding site and guided the design of new analogs. The SAR, pharmacokinetics, brain exposure, and effects on cerebellum D-serine are described. Subsequent evaluation against the rat DAAO enzyme revealed a divergent SAR vs. the human enzyme and may explain the high exposures of drug necessary to achieve significant changes in rat or mouse cerebellum D-serine.
Journal of Medicinal Chemistry published new progress about Cerebellum. 55279-29-3 belongs to class pyridine-derivatives, and the molecular formula is C6H6N2O, COA of Formula: C6H6N2O.