Triazoles as γ-secretase modulators

被引：17

作者：

Fischer, Christian ^{[1
]}

Zultanski, Susan L. ^{[1
]}

Zhou, Hua ^{[1
]}

Methot, Joey L. ^{[1
]}

Brown, W. Colby ^{[1
]}

Mampreian, Dawn M. ^{[1
]}

Schell, Adam J. ^{[1
]}

Shah, Sanjiv ^{[1
]}

Nuthall, Hugh ^{[1
]}

Hughes, Bethany L. ^{[1
]}

Smotrov, Nadja ^{[1
]}

Kenific, Candia M. ^{[1
]}

Cruz, Jonathan C. ^{[1
]}

Walker, Deborah ^{[1
]}

Bouthillette, Melanie ^{[1
]}

Nikov, George N. ^{[1
]}

Savage, Dan F. ^{[1
]}

Jeliazkova-Mecheva, Valentina V. ^{[1
]}

Diaz, Damaris ^{[1
]}

Szewczak, Alexander A. ^{[1
]}

Bays, Nathan ^{[1
]}

Middleton, Richard E. ^{[1
]}

Munoz, Benito ^{[1
]}

Shearman, Mark S. ^{[1
]}

机构：

[1] Merck Res Labs Boston, Boston, MA 02115 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 13期

关键词：

Alzheimer; Secretase; GSM; Abeta lowering; Lead optimization; MEDICINAL CHEMISTRY; ALZHEIMERS-DISEASE; DERIVATIVES; INHIBITORS; PRECURSOR;

D O I：

10.1016/j.bmcl.2011.04.089

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Synthesis, SAR, and evaluation of aryl triazoles as novel gamma secretase modulators (GSMs) are presented in this communication. Starting from the literature and in-house leads, we evaluated a range of five-membered heterocycles as replacements for olefins commonly found in non-acid GSMs. 1,2,3-C-aryl-triazoles were identified as suitable replacements which exhibited good modulation of gamma-secretase activity, excellent pharmacokinetics and good central lowering of A beta 42 in Sprague-Dawley rats. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：4083 / 4087

页数：5

共 38 条

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[Anonymous], ALZH DIS FACTS FIG

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