1350604-45-3Relevant academic research and scientific papers
Synthesis and preliminary biological evaluation of potent and selective 2-(3-alkoxy-1-azetidinyl) quinolines as novel PDE10A inhibitors with improved solubility
Rzasa, Robert M.,Frohn, Michael J.,Andrews, Kristin L.,Chmait, Samer,Chen, Ning,Clarine, Jeffrey G.,Davis, Carl,Eastwood, Heather A.,Horne, Daniel B.,Hu, Essa,Jones, Adrie D.,Kaller, Matthew R.,Kunz, Roxanne K.,Miller, Silke,Monenschein, Holger,Nguyen, Thomas,Pickrell, Alexander J.,Porter, Amy,Reichelt, Andreas,Zhao, Xiaoning,Treanor, James J.S.,Allen, Jennifer R.
, p. 6570 - 6585 (2015/02/19)
We report the discovery of a novel series of 2-(3-alkoxy-1-azetidinyl) quinolines as potent and selective PDE10A inhibitors. Structure-activity studies improved the solubility (pH 7.4) and maintained high PDE10A activity compared to initial lead compound 3, with select compounds demonstrating good oral bioavailability. X-ray crystallographic studies revealed two distinct binding modes to the catalytic site of the PDE10A enzyme. An ex vivo receptor occupancy assay in rats demonstrated that this series of compounds covered the target within the striatum.
HETEROARYLOXYHETEROCYCLYL COMPOUNDS AS PDE10 INHIBITORS
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Page/Page column 171, (2011/12/02)
Heteroaryloxyheterocyclyl compounds, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, Huntington's Disease, bipolar disorder, obsessive-compulsive disorder, and the like.
