National Center for
4PZX: Synthesis, Characterization And Pk/pd Studies Of A Series Of Spirocyclic Pyranochromene Bace1 Inhibitors
Synthesis, characterization, and PK/PD studies of a series of spirocyclic pyranochromene BACE1 inhibitors
Bioorg. Med. Chem. Lett. (2014) 24 p.2477-2480
The development of 1,3,4,4a,5,10a-hexahydropyrano[3,4-b]chromene analogs as BACE1 inhibitors is described. Introduction of the spirocyclic pyranochromene scaffold yielded several advantages over previous generation cores, including increased potency, reduced efflux, and reduced CYP2D6 inhibition. Compound 13 (BACE1 IC50=110 nM) demonstrated a reduction in CSF Abeta in wild type rats after a single dose.