Claffey, Michelle M. published the artcileApplication of Structure-Based Drug Design and Parallel Chemistry to Identify Selective, Brain Penetrant, In Vivo Active Phosphodiesterase 9A Inhibitors, Recommanded Product: 3-Phenoxyazetidine hydrochloride, the main research area is structure preparation phosphodiesterase 9A inhibitor brain penetration Alzheimer’s t.
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.
Journal of Medicinal Chemistry published new progress about Alzheimer disease. 301335-39-7 belongs to class ethers-buliding-blocks, name is 3-Phenoxyazetidine hydrochloride, and the molecular formula is C9H12ClNO, Recommanded Product: 3-Phenoxyazetidine hydrochloride.
Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem