| Literature DB >> 21269825 |
Michael A Brodney1, David D Auperin, Stacey L Becker, Brian S Bronk, Tracy M Brown, Karen J Coffman, James E Finley, Carol D Hicks, Michael J Karmilowicz, Thomas A Lanz, Dane Liston, Xingrong Liu, Barbara-Anne Martin, Robert B Nelson, Charles E Nolan, Christine E Oborski, Christine P Parker, Karl E G Richter, Nikolay Pozdnyakov, Barbara G Sahagan, Joel B Schachter, Sharon A Sokolowski, Barbara Tate, Jeffrey W Van Deusen, Douglas E Wood, Kathleen M Wood.
Abstract
The synthesis and structure-activity relationship (SAR) of a novel series of di-substituted imidazoles, derived from modification of DAPT, are described. Subsequent optimization led to identification of a highly potent series of inhibitors that contain a β-amine in the imidazole side-chain resulting in a robust in vivo reduction of plasma and brain Aβ in guinea pigs. The therapeutic index between Aβ reductions and changes in B-cell populations were studied for compound 10 h.Entities:
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Year: 2010 PMID： 21269825 DOI： 10.1016/j.bmcl.2010.12.117
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823