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ID: ALA1146699

Journal: Bioorg Med Chem Lett

Title: P3 cap modified Phe*-Ala series BACE inhibitors.

Authors: Chen SH, Lamar J, Guo D, Kohn T, Yang HC, McGee J, Timm D, Erickson J, Yip Y, May P, McCarthy J.

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 P3NHBoc 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 IC(50) <50 nM) and whole cell activities (IC(50) approximately 1 microM).

CiteXplore: 14684336

DOI: 10.1016/j.bmcl.2003.09.085