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ID: ALA1147000

Journal: Bioorg Med Chem Lett

Title: Synthesis and evaluation of succinoyl-caprolactam gamma-secretase inhibitors.

Authors: Thompson LA, Liauw AY, Ramanjulu MM, Kasireddy-Polam P, Mercer SE, Maduskuie TP, Glicksman M, Roach AH, Meredith JE, Liu RQ, Combs AP, Higaki JN, Cordell B, Seiffert D, Zaczek RC, Robertson DW, Olson RE.

Abstract: The synthesis, evaluation, and structure-activity relationships of a series of succinoyl lactam inhibitors of the Alzheimer's disease gamma-secretase are described. Beginning with a screening hit with broad proteinase activity, optimization provided compounds with both high selectivity for inhibition of gamma-secretase and high potency in cellular assays of A beta reduction. The SAR and early in vivo properties of this series of inhibitors will be presented.

CiteXplore: 16473009

DOI: 10.1016/j.bmcl.2006.01.055