Diamide amino-imidazoles: a novel series of γ-secretase inhibitors for the treatment of Alzheimer's disease.

Autor: Brodney MA; Neuroscience Medicinal Chemistry, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA. michael.a.brodney@pfizer.com, Auperin DD, Becker SL, Bronk BS, Brown TM, Coffman KJ, Finley JE, Hicks CD, Karmilowicz MJ, Lanz TA, Liston D, Liu X, Martin BA, Nelson RB, Nolan CE, Oborski CE, Parker CP, Richter KE, Pozdnyakov N, Sahagan BG, Schachter JB, Sokolowski SA, Tate B, Van Deusen JW, Wood DE, Wood KM
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2011 May 01; Vol. 21 (9), pp. 2631-6. Date of Electronic Publication: 2010 Dec 30.
DOI: 10.1016/j.bmcl.2010.12.117
Abstrakt: 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.
(Copyright © 2011 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: