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

共 50 条

[1] Potential protease inhibitors based on a functionalized cyclic sulfamide scaffold
Zhong, JY
Gan, XD
Alliston, KR
Lai, Z
Yu, HY
Groutas, CS
Wong, TS
Groutas, WC
JOURNAL OF COMBINATORIAL CHEMISTRY, 2004, 6 (04): : 556 - 563
[2] Cyclic phenylstatine-based tetrapeptides as inhibitors of β-secretase
Barazza, A
Renner, C
Willem, M
Moroder, L
BIOPOLYMERS, 2005, 80 (04) : 554 - 554
[3] Cyclic statine-based peptides as inhibitors of β-secretase
Barazza, Alessandra
Goetz, Marion
Renner, Christian
Willem, Michael
Moroder, Luis
UNDERSTANDING BIOLOGY USING PEPTIDES, 2006, : 385 - +
[4] Substituted cyclic ether arylsulfonamides as potent inhibitors of g-secretase
Karki, Kapil
Stepan, Antonia F.
Becker, Stacey
Capetta, Steven
DiRico, Kenneth
O'Donnell, Christopher
Dorff, Peter
Dutra, Jason K.
Efremov, Ivan
Green, Michael
Kauffman, Gregory
Kormos, Bethany L.
McDonald, W. Scott
Nolan, Charles
Obach, Scott
Pustilnik, Leslie
Riddell, David
Sibley, Evelyn
Sneed, Blossom
Subramanyam, Chakrapani
Sun, Hao
O'Sullivan, Theresa
Won, Annie
Zhang, Liming
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2011, 242
[5] Synthesis and Biological Evaluation of Cyclic Sulfamide Derivatives as 11β-Hydroxysteroid Dehydrogenase 1 Inhibitors
Kim, Se Hoan
Bok, Ju Han
Lee, Jae Hong
Kim, Il Hyang
Kwon, Sung Wook
Lee, Gui Bin
Kang, Seung Kyu
Park, Ji Seon
Jung, Won Hoon
Kim, Hee Yeon
Rhee, Sang Dal
Ahn, Sung Hoon
Bae, Myung Ae
Ha, Deok Chan
Kim, Ki Young
Ahn, Jin Hee
ACS MEDICINAL CHEMISTRY LETTERS, 2012, 3 (02): : 88 - 93
[6] β-SECRETASE INHIBITORS
不详
CHEMICAL & ENGINEERING NEWS, 2016, : 21 - 21
[7] The sulfamide motif in the design of enzyme inhibitors
Winum, JY
Scozzafava, A
Montero, JL
Supuran, CT
EXPERT OPINION ON THERAPEUTIC PATENTS, 2006, 16 (01) : 27 - 47
[8] Design, synthesis, and in vitro evaluation of inhibitors of human leukocyte elastase based on a functionalized cyclic sulfamide scaffold
Zhong, JY
Gan, XD
Alliston, KR
Groutas, WC
BIOORGANIC & MEDICINAL CHEMISTRY, 2004, 12 (03) : 589 - 593
[9] Inhibitors and modulators of β- and γ-secretase
Schmidt, Boris
Baumann, Stefanie
Braun, Hannes A.
Larbig, Gregor
CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2006, 6 (04) : 377 - 392
[10] γ-Secretase inhibitors and modulators
Golde, Todd E.
Koo, Edward H.
Felsenstein, Kevin M.
Osborne, Barbara A.
Miele, Lucio
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 2013, 1828 (12): : 2898 - 2907

← 1 2 3 4 5 →