Author/Authors :
Shu-Hui Chen، نويسنده , , Jason Lamar، نويسنده , , Deqi Guo، نويسنده , , Todd Kohn، نويسنده , , Hsiu-Chiung Yang، نويسنده , , James McGee، نويسنده , , David Timm، نويسنده , , Jon Erickson، نويسنده , , Yvonne Yip، نويسنده , , Patrick May، نويسنده , , James McCarthy، نويسنده ,
Abstract :
With the aim of reducing molecular weight and adjusting log D value of BACE inhibitors to more favorable range for BBB penetration and better bioavailability, we synthesized and evaluated several series of P3 cap modified BACE inhibitors obtained via replacement of the P3 NHBoc moiety as seen in 3 with other polar functional groups such as amino, hydroxyl and fluorine. Several promising inhibitors emerging from this P3 cap SAR study (e.g., 15 and 19) demonstrated good enzyme inhibitory potencies (BACE-1 IC50<50 nM) and whole cell activities (IC50 1 μM).
