Application of Structure-Based Drug Design and Parallel Chemistry to Identify Selective, Brain Penetrant, In Vivo Active Phosphodiesterase 9A Inhibitors was written by Claffey, Michelle M.;Helal, Christopher J.;Verhoest, Patrick R.;Kang, Zhijun;Bundesmann, Mark W.;Hou, Xinjun;Lui, Shenping;Kleiman, Robin J.;Vanase-Frawley, Michelle;Schmidt, Anne W.;Menniti, Frank;Schmidt, Christopher J.;Hoffman, William E.;Hajos, Mihaly;McDowell, Laura;O’Connor, Rebecca E.;MacDougall-Murphy, Mary;Fonseca, Kari R.;Becker, Stacey L.;Nelson, Frederick R.;Liras, Spiros. And the article was included in Journal of Medicinal Chemistry in 2012.Recommanded Product: 2-Fluoro-5-hydroxybenzenecarbonitrile This article mentions the following:
Phosphodiesterase 9A inhibitors have shown activity in preclin. models of cognition with potential application as novel therapies for treating Alzheimer’s disease. Our clin. candidate, PF-04447943 (2), demonstrated acceptable CNS permeability in rats with modest asymmetry between central and peripheral compartments (free brain/free plasma = 0.32; CSF/free plasma = 0.19) yet had physicochem. properties outside the range associated with traditional CNS drugs. To address the potential risk of restricted CNS penetration with 2 in human clin. trials, we sought to identify a preclin. candidate with no asymmetry in rat brain penetration and that could advance into development. Merging the medicinal chem. strategies of structure-based design with parallel chem., a novel series of PDE9A inhibitors was identified that showed improved selectivity over PDE1C. Optimization afforded preclin. candidate 19 that demonstrated free brain/free plasma ≥1 in rat and reduced microsomal clearance along with the ability to increase cyclic guanosine monophosphosphate levels in rat CSF. In the experiment, the researchers used many compounds, for example, 2-Fluoro-5-hydroxybenzenecarbonitrile (cas: 104798-53-0Recommanded Product: 2-Fluoro-5-hydroxybenzenecarbonitrile).
2-Fluoro-5-hydroxybenzenecarbonitrile (cas: 104798-53-0) belongs to nitriles. Nitriles are polar, as indicated by high dipole moments. As liquids, they have high relative permittivities, often in the 30s. Nitrile groups in organic compounds can undergo a variety of reactions depending on the reactants or conditions. A nitrile group can be hydrolyzed, reduced, or ejected from a molecule as a cyanide ion.Recommanded Product: 2-Fluoro-5-hydroxybenzenecarbonitrile
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts