Discovery of a novel [3.2.1] benzo fused bicyclic sulfonamide-pyrazoles as potent, selective and efficacious γ-secretase inhibitors

被引：10

作者：

Ye, Xiaocong M. ^{[1
]}

Konradi, Andrei W. ^{[1
]}

Sun, Minghua ^{[1
]}

Yuan, Shendong ^{[1
]}

Aubele, Danielle L. ^{[1
]}

Dappen, Michael ^{[1
]}

Dressen, Darren ^{[1
]}

Garofalo, Albert W. ^{[1
]}

Jagodzinski, Jacek J. ^{[1
]}

Latimer, Lee ^{[1
]}

Probst, Gary D. ^{[1
]}

Sham, Hing L. ^{[1
]}

Wone, David ^{[1
]}

Xu, Ying-zi ^{[1
]}

Ness, Daniel ^{[2
]}

Brigham, Elizabeth ^{[2
]}

Kwong, Grace T. ^{[2
]}

Willtis, Chris ^{[2
]}

Tonn, George ^{[3
]}

Goldbach, Erich ^{[3
]}

Quinn, Kevin P. ^{[3
]}

Zhang, Hongbin H. ^{[3
]}

Sauer, John-Michael ^{[3
]}

Bova, Michael ^{[4
]}

Basi, Guriqbal S. ^{[5
]}

机构：

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

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

[3] Elan Pharmaceut, Dept Drug Metab & Pharmacokinet, San Francisco, CA 94080 USA

[4] Elan Pharmaceut, Dept Assay Dev, San Francisco, CA 94080 USA

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2013年 / 23卷 / 04期

关键词：

Alzheimer's disease; Amyloid precursor protein; gamma-Secretase; gamma-Secretase inhibitor; Notch; ALZHEIMERS-DISEASE; GENES;

D O I：

10.1016/j.bmcl.2012.12.039

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Structure-activity relationship (SAR) of a novel, potent and metabolically stable series of benzo [3.2.1] bicyclic sulfonamide-pyrazoles as gamma-secretase inhibitors are described. Compounds that are efficacious in reducing the cortical A beta x-40 levels in FVB mice via oral dose, as well as those with high selectivity over Notch, are highlighted. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：996 / 1000

页数：5

共 50 条

[1] Design, synthesis and structure-activity relationship of novel [3.3.1] bicyclic sulfonamide-pyrazoles as potent γ-secretase inhibitors
Aubele, Danielle L.
Truong, Anh P.
Dressen, Darren B.
Probst, Gary D.
Bowers, Simeon
Mattson, Matthew N.
Semko, Chris M.
Sun, Minghua
Garofalo, Albert W.
Konradi, Andrei W.
Sham, Hing L.
Zmolek, Wes
Wong, Karina
Goldbach, Erich
Quinn, Kevin P.
Sauer, John-Michael
Brigham, Elizabeth F.
Wallace, William
Nguyen, Lan
Bova, Michael P.
Hemphill, Susanna S.
Basi, Guriqbal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2011, 21 (19) : 5791 - 5794
[2] 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
[3] Discovery of a novel sulfonamide-pyrazolopiperidine series as potent and efficacious γ-secretase inhibitors (Part II)
Ye, Xiaocong M.
Konradi, Andrei W.
Smith, Jenifer
Aubele, Danielle L.
Garofalo, Albert W.
Marugg, Jennifer
Neitzel, Marty L.
Semko, Chris M.
Sham, Hing L.
Sun, Minghua
Truong, Anh P.
Wu, Jing
Zhang, Hongbin
Goldbach, Erich
Sauer, John-Michael
Brigham, Elizabeth F.
Bova, Michael
Basi, Guriqbal S.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (12) : 3502 - 3506
[4] Discovery of novel, potent γ-secretase inhibitors
Zhao, Zhiqiang
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2015, 249
[5] Discovery of Novel Bicyclic Pyrazoles as Potent PIP5K1C Inhibitors
Ochiai, Koji
Seto, Shigeki
Yajima, Masanobu
Namie, Ryosuke
Hashimoto, Noriaki
Fujita, Motomichi
Yokoyama, Akinobu
Suezawa, Takahiro
Matsui, Hitomi
Tomizawa, Satoshi
Ishibashi, Yuji
Tanaka, Yuta
Yajima, Miho
Nagasawa, Michiaki
Ando, Naoki
ACS MEDICINAL CHEMISTRY LETTERS, 2024, 15 (05): : 684 - 690
[6] 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
[7] Discovery and optimization of potent, selective, and in vivo efficacious BCATm inhibitors
Deng, Hongfeng
Zhou, Jingye
Sundersingh, Flora
Messer, Jeff
Somers, Don
Beljean, Arthur
Belyanskaya, Svetlana
Bingham, Ryan
Blazensky, Emily
Boursier, Eric
Chai, Jing
Carter, Paul
Chung, Chun-wa
Daugan, Alain
Ding, Yun
Humphries, Eric
Kollmann, Chris
Smith, Sarah
Dodic, Nerina
Ancellin, Nicolas
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2015, 250
[8] Discovery of tetrahydroindazoles as a novel class of potent and in vivo efficacious gamma secretase modulators
Gerlach, Kai
Hobson, Scott
Eickmeier, Christian
Gross, Ulrike
Braun, Clemens
Sieger, Peter
Garneau, Michel
Hoerer, Stefan
Heine, Niklas
BIOORGANIC & MEDICINAL CHEMISTRY, 2018, 26 (12) : 3227 - 3241
[9] Trifluoromethyl oxazines as highly potent and selective beta-secretase inhibitors that are efficacious in vivo
Cheng, Yuan
Xue, May
Judd, Ted
Lopez, Patricia
Low, Jon
Minatti, Ana
Qian, Wenyuan
Liu, Qingyian
Chen, Ning
Zhong, Wenge
Liu, Longbin
Amegadzie, Albert
Rumfelt, Shannon
Rzasa, Robert
Bartberger, Michael
Chen, Kui
Hickman, Dean
Nanez, Adrian
Tan, Helming
Volak, Laurie
Wen, Paul
Whittington, Douglas
Wood, Stephen
Allen, Jennifer
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2015, 250
[10] Optimization of a heteroaryl sulfonamide series of potent, selective and efficacious Nav1.7 inhibitors
Weiss, Matthew
Boezio, Alessandro
Butler, John
Dineen, Thomas
Graceffa, Russell
Kreiman, Charles
Kornecook, Thomas
La, Daniel
Marx, Isaac
Milgram, Benjamin
Sparling, Brian
Moyer, Bryan
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2016, 252

← 1 2 3 4 5 →