Discovery of a novel series of Notch-sparing γ-secretase inhibitors

被引：20

作者：

Kreft, Anthony ^{[1
]}

Harrison, Boyd ^{[1
]}

Aschmies, Suzan ^{[2
]}

Atchison, Kevin ^{[2
]}

Casebier, David ^{[4
]}

Cole, Derek C. ^{[1
]}

Diamantidis, George ^{[1
]}

Ellingboe, John ^{[1
]}

Hauze, Diane ^{[1
]}

Hu, Yun ^{[2
]}

Huryn, Donna ^{[1
]}

Jin, Mei ^{[2
]}

Kubrak, Dennis ^{[1
]}

Lu, Peimin ^{[2
]}

Lundquist, Joseph ^{[1
]}

Mann, Charles ^{[1
]}

Martone, Robert ^{[2
]}

Moore, William ^{[4
]}

Oganesian, Aram ^{[3
]}

Porte, Alex ^{[1
]}

Riddell, Dave R. ^{[2
]}

Sonnenberg-Reines, June ^{[2
]}

Stock, Joseph R. ^{[1
]}

Sun, Shaiu-Ching ^{[2
]}

Wagner, Erik ^{[2
]}

Woller, Kevin ^{[4
]}

Xu, Zheng ^{[2
]}

Zhou, Hua ^{[2
]}

Jacobsen, J. Steven ^{[2
]}

机构：

[1] Wyeth Ayerst Res, Chem & Screening Sci, Princeton, NJ 08543 USA

[2] Wyeth Ayerst Res, Discovery Neurosci, Princeton, NJ 08543 USA

[3] Wyeth Ayerst Res, Drug Safety & Metab, Collegeville, PA 19426 USA

[4] ArQule Inc, Woburn, MA 01801 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 14期

基金：

美国国家卫生研究院;

关键词：

Alzheimer's disease; gamma-secretase; Notch; amyloid; protease inhibitor;

D O I：

10.1016/j.bmcl.2008.05.064

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Using a cell-based assay, we have identified a new series of Notch-sparing gamma-secretase inhibitors from HTS screening leads 2a and 2e. Lead optimization studies led to the discovery of analog 8e with improved gamma-secretase inhibitory potency and Notch-sparing selectivity. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：4232 / 4236

页数：5

共 50 条

[1] Discovery of Notch-Sparing γ-Secretase Inhibitors
Augelli-Szafran, C. E.
Wei, H. -X.
Lu, D.
Zhang, J.
Gu, Y.
Yang, T.
Osenkowski, P.
Ye, W.
Wolfe, M. S.
CURRENT ALZHEIMER RESEARCH, 2010, 7 (03) : 207 - 209
[2] Discovery of small molecular (D)-leucinamides as potent, Notch-sparing γ-secretase modulators
Liao, Yung-Feng
Tang, Yu-Cheng
Chang, Ming-Yun
Wang, Bo-Jeng
Hu, Ming-Kuan
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2014, 79 : 143 - 151
[3] Part 1: Notch-sparing γ-secretase inhibitors: The identification of novel naphthyl and benzofuranyl amide analogs
Lu, Dai
Wei, Han-Xun
Zhang, Jing
Gu, Yongli
Osenkowski, Pamela
Ye, Wenjuan
Selkoe, Dennis J.
Wolfe, Michael S.
Augelli-Szafran, Corinne E.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2016, 26 (09) : 2129 - 2132
[4] Part 2. Notch-sparing γ-secretase inhibitors: The study of novel γ-amino naphthyl alcohols
Wei, Han-Xun
Lu, Dai
Sun, Vivien
Zhang, Jing
Gu, Yongli
Osenkowski, Pamela
Ye, Wenjuan
Selkoe, Dennis J.
Wolfe, Michael S.
Augelli-Szafran, Corinne E.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2016, 26 (09) : 2133 - 2137
[5] Novel Notch-sparing γ-secretase inhibitors derived from a peroxisome proliferator-activated receptor agonist library
Kurosumi, Motonori
Nishio, Yoshino
Osawa, Satoko
Kobayashi, Hisayoshi
Iwatsubo, Takeshi
Tomita, Taisuke
Miyachi, Hiroyuki
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (17) : 5282 - 5285
[6] MEDI 245-Optimization of the in vivo activity of potent, Notch-sparing gamma secretase inhibitors
Kreft, Anthony
Harrison, Boyd L.
Abou-Gharbia, Magid
Afragola, Jay
Alimardinov, Asaf
Antane, Madelene
Aschmies, Suzan
Atchison, Kevin
Caggiano, Thomas
Chlenov, Michael
Cole, Derek
Comery, Thomas
Diamantidis, George
Ellingboe, John
Fan, Kristi
Gonzalez, Cathleen
Hauze, Diane
Hoke, Molly
Hu, Yun
Huang, Xinyi
Huryn, Donna
Jain, Uday
Jin, Mei
Khafizova, Gulnaz
Kubrak, Dennis
Kutterer, Kristina
Lin, Melissa
Lu, Peimin
Lundquist, Joseph
Magolda, Ronald L.
Mann, Charles
Martone, Robert
May, Michael
Mayer, Scott
Mehlmann, John
Moore, William J.
Morris, Koi
Oganesian, Aram
Pangalos, Menelas
Porte, Alex
Reinhart, Peter
Resnick, Lynn
Riddell, David R.
Schmid, Jean
Sonnenberg-Reines, June
Stock, Joseph
Sun, Roy
Wagner, Erik
Wang, Zheng
Woller, Kevin
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2007, 234
[7] Part 3: Notch-sparing γ-secretase inhibitors: SAR studies of 2-substituted aminopyridopyrimidinones
Zhang, Jing
Lu, Dai
Wei, Han-Xun
Gu, Yongli
Selkoe, Dennis J.
Wolfe, Michael S.
Augelli-Szafran, Corinne E.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2016, 26 (09) : 2138 - 2141
[8] Discovery of a Novel, Potent Spirocyclic Series of γ-Secretase Inhibitors
Zhao, Zhiqiang
Pissarnitski, Dmitri A.
Josien, Hubert B.
Wu, Wen-Lian
Xu, Ruo
Li, Hongmei
Clader, John W.
Burnett, Duane A.
Terracina, Giuseppe
Hyde, Lynn
Lee, Julie
Song, Lixin
Zhang, Lili
Parker, Eric M.
JOURNAL OF MEDICINAL CHEMISTRY, 2015, 58 (22) : 8806 - 8817
[9] Discovery of novel, potent γ-secretase inhibitors
Zhao, Zhiqiang
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2015, 249
[10] Discovery of a novel sulfonamide-pyrazolopiperidine series as potent and Efficacious γ-Secretase Inhibitors
Ye, Xiaocong M.
Konradi, Andrei W.
Smith, Jenifer
Xu, Ying-Zi
Dressen, Darren
Garofalo, Albert W.
Marugg, Jennifer
Sham, Hing L.
Truong, Anh P.
Jagodzinski, Jacek
Pleiss, Michael
Zhang, Hongbin
Goldbach, Erich
Sauer, John-Michael
Brigham, Elizabeth
Bova, Michael
Basi, Guriqbal S.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (07) : 2195 - 2199

← 1 2 3 4 5 →