Cyclic sulfamide γ-secretase inhibitors

被引：54

作者：

Sparey, T

Beher, D

Best, J

Biba, M

Castro, JL

Clarke, E

Hannam, J

Harrison, T

Lewis, H

Madin, A

Shearman, M

Sohal, B

Tsou, N

Welch, C

Wrigley, J

机构：

[1] Merck Sharp & Dohme Res Labs, Neurosci Res Ctr, Dept Med Chem, Harlow CM20 2QR, Essex, England

[2] Merck Sharp & Dohme Res Labs, Neurosci Res Ctr, Dept Cellular & Mol Neurosci, Harlow CM20 2QR, Essex, England

[3] Merck Sharp & Dohme Res Labs, Neurosci Res Ctr, Dept In Vivo Neurosci, Harlow CM20 2QR, Essex, England

[4] Merck Res Labs, Dept Proc Res, Rahway, NJ 07065 USA

[5] Merck Res Labs, Dept Med Chem, Rahway, NJ 07065 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 19期

关键词：

Alzheimer's disease; gamma-secretase inhibitor; cyclic sulfamide;

D O I：

10.1016/j.bmcl.2005.06.084

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of N-alkyl-substituted cyclic sulfamides were developed from a screening hit. Chemistries were developed which allowed surveys of N-alkyl groups and amines resulting in the identification of N-trifluoroethyl-substituted cyclic sulfamides with good in vitro and in vivo gamma-secretase activity. One compound with subnanomolar activity elicited a reduction in brain A beta 40 after oral dosing in APP-YAC mice. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：4212 / 4216

页数：5

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