Discovery of an Orally Bioavailable, Brain-Penetrating, in Vivo Active Phosphodiesterase 2A Inhibitor Lead Series for the Treatment of Cognitive Disorders was written by Mikami, Satoshi;Sasaki, Shigekazu;Asano, Yasutomi;Ujikawa, Osamu;Fukumoto, Shoji;Nakashima, Kosuke;Oki, Hideyuki;Kamiguchi, Naomi;Imada, Haruka;Iwashita, Hiroki;Taniguchi, Takahiko. And the article was included in Journal of Medicinal Chemistry in 2017.Related Products of 130339-50-3 The following contents are mentioned in the article:
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. This study involved multiple reactions and reactants, such as 1-(4-(Trifluoromethoxy)phenyl)propan-1-amine (cas: 130339-50-3Related Products of 130339-50-3).
1-(4-(Trifluoromethoxy)phenyl)propan-1-amine (cas: 130339-50-3) belongs to ethers. Esters are also usually derived from carboxylic acids. It may also be obtained by reaction of acid anhydride or acid halides with alcohols or by the reaction of salts of carboxylic acids with alkyl halides. Many esters have the potential for conformational isomerism, but they tend to adopt an s-cis (or Z) conformation rather than the s-trans (or E) alternative, due to a combination of hyperconjugation and dipole minimization effects. The preference for the Z conformation is influenced by the nature of the substituents and solvent, if present. Lactones with small rings are restricted to the s-trans (i.e. E) conformation due to their cyclic structure.Related Products of 130339-50-3
Referemce:
Ether – Wikipedia,
Ether | (C2H5)2O – PubChem