N-(3-(2-amino-6,6-difluoro-4,4a,5,6,7,7a-hexahydro-cyclopenta[e][1,3]oxazin-4-yl)-phenyl)-amides as BACE1 inhibitors: a patent evaluation of WO2013041499

Abstract

A new series of oxazin amides have been synthesized from isoxazoles using a reaction to increase the heterocyclic ring size and were evaluated as BACE1 inhibitors. The innovative compounds were able to diminish amyloid-β peptide concentration in cell and proved to be selective toward peptidases from the same family. Further studies on the toxicity of this series showed that these new molecules were not recognized by P-glycoprotein and that they were unsusceptible to rapid metabolization by cytochrome P450 or glutathione conjugation. These results indicate that such compounds could be useful in developing drugs to fight Alzheimer's disease and that this novel oxazin scaffold should be considered as a starting point to tackle this pathology.

Tandem CuAAC/Ring Cleavage/[4 + 2] Annulation Reaction to Synthesize Dihydrooxazines and Conversion to 2-Aminopyrimidines

“…On the contrary, oxazine counterparts or derivatives often occur in natural products and have been commonly investigated as biological agents . One subset of such compounds is the 1,3-oxazin-4-ones, which have shown these heterocycles to possess potent anticancer, antibacterial, and anti-inflammatory properties .…”