Mikami, Satoshi published the artcileDiscovery of an Orally Bioavailable, Brain-Penetrating, in Vivo Active Phosphodiesterase 2A Inhibitor Lead Series for the Treatment of Cognitive Disorders, Application In Synthesis of 23286-70-6, the publication is Journal of Medicinal Chemistry (2017), 60(18), 7658-7676, database is CAplus and MEDLINE.
Herein, the authors describe the discovery of a potent, selective, brain-penetrating, in vivo active phosphodiesterase (PDE) 2A inhibitor lead series. To identify high-quality leads suitable for optimization and enable validation of the physiol. function of PDE2A in vivo, structural modifications of the high-throughput screening hit were performed. The lead generation efforts revealed three key potency-enhancing functionalities with minimal increases in mol. weight (MW) and no change in topol. polar surface area (TPSA). Combining these structural elements led to the identification of 6-methyl-N-((1R)-1-(4-(trifluoromethoxy)phenyl)propyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (38a), a mol. with the desired balance of preclin. properties. Further characterization by cocrystal structure anal. of (38a) bound to PDE2A uncovered a unique binding mode and provided insights into its observed potency and PDE selectivity. Compound (38a) significantly elevated 3′,5′-cGMP levels in mouse brain following oral administration, thus validating this compound as a useful pharmacol. tool and an attractive lead for future optimization.
Journal of Medicinal Chemistry published new progress about 23286-70-6. 23286-70-6 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Amine,Ester, name is Ethyl 5-amino-3-methyl-1H-pyrazole-4-carboxylate, and the molecular formula is C7H11N3O2, Application In Synthesis of 23286-70-6.
Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics