Amino-caprolactam γ-secretase inhibitors showing potential for the treatment of Alzheimer's disease

被引：6

作者：

Neitzel, Martin L. ^{[1
]}

Aubele, Danielle L. ^{[1
]}

Marugg, Jennifer L. ^{[1
]}

Jagodzinski, Jacek J. ^{[1
]}

Konradi, Andrei W. ^{[1
]}

Pleiss, Michael A. ^{[1
]}

Szoke, Balazs ^{[2
]}

Zmolek, Wes ^{[2
]}

Goldbach, Erich ^{[2
]}

Quinn, Kevin P. ^{[2
]}

Sauer, John-Michael ^{[2
]}

Brigham, Elizabeth F. ^{[4
]}

Wallace, William ^{[3
]}

Bova, Michael P. ^{[3
]}

Hemphill, Susanna ^{[3
]}

Basi, Guriqbal ^{[3
]}

机构：

[1] Elan Pharmaceut, Dept Med Chem, San Francisco, CA 94080 USA

[2] Elan Pharmaceut, Dept Lead Finding Drug Disposit & Safety Elvaluat, San Francisco, CA 94080 USA

[3] Elan Pharmaceut, Dept Biol, San Francisco, CA 94080 USA

[4] Elan Pharmaceut, Dept Vivo Pharmacol, San Francisco, CA 94080 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 12期

关键词：

gamma-Secretase inhibitor; Alzheimer's disease; beta-Amyloid; Notch; Amino-caprolactam; DESIGN;

D O I：

10.1016/j.bmcl.2011.04.079

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Herein we describe the structure-activity relationship (SAR) of amino-caprolactam analogs derived from amino-caprolactam benzene sulfonamide 1, highlighting affects on the potency of gamma-secretase inhibition, selectivity for the inhibition of APP versus Notch processing by gamma-secretase and selected pharmakokinetic properties. Amino-caprolactams that are efficacious in reducing the cortical A beta(x-40) levels in FVB mice via a single 100 mpk IP dose are highlighted. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：3715 / 3720

页数：6

共 50 条

[21] Development of semagacestat (LY450139), a functional γ-secretase inhibitor, for the treatment of Alzheimer's disease [J].

Henley, David B. ;

May, Patrick C. ;

Dean, Robert A. ;

Siemers, Eric R. .

EXPERT OPINION ON PHARMACOTHERAPY, 2009, 10 (10) :1657-1664

[22] Recent developments of structure based β-secretase inhibitors for Alzheimer's disease [J].

Ghosh, AK ;

Kumaragurubaran, N ;

Tang, J .

CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2005, 5 (16) :1609-1622

[23] LMP2 Inhibitors as a Potential Treatment for Alzheimer's Disease [J].

Bhattarai, Deepak ;

Lee, Min Jae ;

Baek, Ahruem ;

Yeo, In Jun ;

Miller, Zachary ;

Baek, Yu Mi ;

Lee, Sukyeong ;

Kim, Dong-Eun ;

Hong, Jin Tae ;

Kim, Kyung Bo .

JOURNAL OF MEDICINAL CHEMISTRY, 2020, 63 (07) :3763-3783

[24] GSK-3 inhibitors and their potential in the treatment of Alzheimer's disease [J].

Kypta, RM .

EXPERT OPINION ON THERAPEUTIC PATENTS, 2005, 15 (10) :1315-1331

[25] The potential for BACE1 inhibitors in the treatment of Alzheimer's disease [J].

Hussain, I .

IDRUGS, 2004, 7 (07) :653-658

[26] Alkaloids as a source of potential anticholinesterase inhibitors for the treatment of Alzheimer's disease [J].

Konrath, Eduardo Luis ;

Passos, Carolina dos Santos ;

Klein-Junior, Luiz Carlos ;

Henriques, Amelia T. .

JOURNAL OF PHARMACY AND PHARMACOLOGY, 2013, 65 (12) :1701-1725

[27] Computational modelling of potent β-secretase (BACE1) inhibitors towards Alzheimer's disease treatment [J].

Ugbaja, Samuel C. ;

Sanusi, Zainab K. ;

Appiah-Kubi, Patrick ;

Lawal, Monsurat M. ;

Kumalo, Hezekiel M. .

BIOPHYSICAL CHEMISTRY, 2021, 270

[28] Evaluation of clinical efficacy of α-secretase in the treatment of Alzheimer's disease [J].

Sun, Yan ;

Chen, Hai ;

Wu, Chengyan .

INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE, 2018, 11 (06) :6076-6081

[29] Discovery of SCH 900229, a Potent Presenilin 1 Selective γ-Secretase Inhibitor for the Treatment of Alzheimer's Disease [J].

Wu, Wen-Lian ;

Domalski, Martin ;

Burnett, Duane A. ;

Josien, Hubert ;

Bara, Thomas ;

Rajagopalan, Murali ;

Xu, Ruo ;

Clader, John ;

Greenlee, William J. ;

Brunskill, Andrew ;

Hyde, Lynn A. ;

Del Vecchio, Robert A. ;

Cohen-Williams, Mary E. ;

Song, Lixin ;

Lee, Julie ;

Terracina, Giuseppe ;

Zhang, Qi ;

Nomeir, Amin ;

Parker, Eric M. ;

Zhang, Lili .

ACS MEDICINAL CHEMISTRY LETTERS, 2012, 3 (11) :892-896

[30] Secretase Inhibitors and Modulators as a Disease-Modifying Approach Against Alzheimer's Disease [J].

Gijsen, Harrie J. M. ;

Bischoff, Francois P. .

ANNUAL REPORTS IN MEDICINAL CHEMISTRY, VOL 47, 2012, 47 :55-69

← 1 2 3 4 5 →