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ID: ALA1145754

Journal: Bioorg Med Chem Lett

Title: Design and synthesis of statine-containing BACE inhibitors.

Authors: Hu J, Cwi CL, Smiley DL, Timm D, Erickson JA, McGee JE, Yang HC, Mendel D, May PC, Shapiro M, McCarthy JR.

Abstract: Utilizing structure-based techniques and solid-phase synthesis, statine-based tetrapeptide BACE inhibitors were designed and synthesized using a heptapeptide BACE transition-state mimetic, 1, as the starting point. Structure-activity relationship studies at the P(3), P(2), and P(2)' positions as well as the N-terminal capping group on scaffold 5 led to the discovery of potent inhibitors 27, 32, and 34 (IC(50) <100 nM). In addition, computational analysis and the X-ray structure of BACE-inhibitor 38 are discussed.

CiteXplore: 14643321

DOI: 10.1016/j.bmcl.2003.09.037