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    Bioorg Med Chem Lett. 2010 Feb 1;20(3):1306-11. Epub 2009 Aug 23.

    Piperidine-derived gamma-secretase modulators.

    Hall A, Elliott RL, Giblin GM, Hussain I, Musgrave J, Naylor A, Sasse R, Smith B.

    Source

    Neurosciences Centre of Excellence for Drug Discovery, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK. adian_hall@eisai.net

    Abstract

    This Letter details the SAR of a novel series of piperidine-derived gamma-secretase modulators. Compound 10h was found to be a potent modulator in vitro, which on further profiling, was found to decrease Abeta42, increase Abeta38 and have no effect on Abeta40 levels. Furthermore, 10h demonstrated excellent pharmacokinetic parameters in the mouse, rat and dog in addition to good CNS penetration in the mouse.

    Copyright (c) 2009. Published by Elsevier Ltd.

    PMID:
    20056541
    [PubMed - indexed for MEDLINE]

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