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

[1] Amino-caprolactam derivatives as γ-secretase inhibitors
Parker, Michael F.
Bronson, Joanne J.
Barten, Donna M.
Corsa, Jason A.
Du, Wengsheng
Felsenstein, Kevin M.
Guss, Valerie L.
Izzarelli, Darcy
Loo, Alice
McElhone, Kate E.
Marcin, Larry R.
Padmanabha, Ramesh
Pak, Roger
Polson, Craig T.
Toyn, Jeremy H.
Varma, Sam
Wang, Jian
Wong, Victoria
Zheng, Ming
RobertSb, Susan B.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (21) : 5790 - 5795
[2] γ-Secretase Inhibitors for the Treatment of Alzheimer's Disease
Wu, Wen-Lian
Zhang, Lili
DRUG DEVELOPMENT RESEARCH, 2009, 70 (02) : 94 - 100
[3] γ-Secretase Inhibitors for the Treatment of Alzheimer's Disease: The Current State
Panza, Francesco
Frisardi, Vincenza
Imbimbo, Bruno P.
Capurso, Cristiano
Logroscino, Giancarlo
Sancarlo, Daniele
Seripa, Davide
Vendemiale, Gianluigi
Pilotto, Alberto
Solfrizzi, Vincenzo
CNS NEUROSCIENCE & THERAPEUTICS, 2010, 16 (05) : 272 - 284
[4] Prospects of -Secretase Inhibitors for the Treatment of Alzheimer's Disease
Ghosh, Arun K.
Tang, Jordan
CHEMMEDCHEM, 2015, 10 (09) : 1463 - 1466
[5] Secretase inhibitors and modulators for Alzheimer's disease treatment
Tomita, Taisuke
EXPERT REVIEW OF NEUROTHERAPEUTICS, 2009, 9 (05) : 661 - 679
[6] γ-Secretase Inhibitors and Modulators for the Treatment of Alzheimer's Disease: Disappointments and Hopes
Imbimbo, Bruno P.
Giardina, Giuseppe A. M.
CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2011, 11 (12) : 1555 - 1570
[7] γ-Secretase inhibitors and Alzheimer's disease
Roberts, SB
ADVANCED DRUG DELIVERY REVIEWS, 2002, 54 (12) : 1579 - 1588
[8] Advances in the identification of γ-secretase inhibitors for the treatment of Alzheimer's disease
D'Onofrio, Grazia
Panza, Francesco
Frisardi, Vincenza
Solfrizzi, Vincenzo
Imbimbo, Bruno P.
Paroni, Giulia
Cascavilla, Leandro
Seripa, Davide
Pilotto, Alberto
EXPERT OPINION ON DRUG DISCOVERY, 2012, 7 (01) : 19 - 37
[9] Developing ß-secretase inhibitors for treatment of Alzheimer's disease
Ghosh, Arun K.
Brindisi, Margherita
Tang, Jordan
JOURNAL OF NEUROCHEMISTRY, 2012, 120 : 71 - 83
[10] Secretase inhibitors for the treatment of Alzheimer's disease: Long road ahead
Kumar, Devendra
Ganeshpurkar, Ankit
Kumar, Dileep
Modi, Gyan
Gupta, Sanjeev Kumar
Singh, Sushil Kumar
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2018, 148 : 436 - 452

← 1 2 3 4 5 →