Pyridine-derived γ-secretase modulators.

Autor: Wan Z; Research and Development, GlaxoSmithKline Pharmaceuticals, 898 Halei Road, Zhangjiang Hi-tech Park, Pudong, Shanghai 201023, China. Zehong.2.Wan@gsk.com, Hall A, Sang Y, Xiang JN, Yang E, Smith B, Harrison DC, Yang G, Yu H, Price HS, Wang J, Hawkins J, Lau LF, Johnson MR, Li T, Zhao W, Mitchell WL, Su X, Zhang X, Zhou Y, Jin Y, Tong Z, Cheng Z, Hussain I, Elliott JD, Matsuoka Y
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2011 Aug 15; Vol. 21 (16), pp. 4832-5. Date of Electronic Publication: 2011 Jun 17.
DOI: 10.1016/j.bmcl.2011.06.042
Abstrakt: SAR of a novel series of pyridine-derived γ-secretase modulators is described. Compound 5 was found to be a potent modulator in vitro, which on further profiling, was found to decrease Aβ42 and Aβ40, and maintain (or increase) the levels of total Aβ. Furthermore, representative compounds 1 and 5 demonstrated in vivo efficacy to lower Aβ42 in the brain without altering Notch processing in the peripheral.
(Copyright © 2011 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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