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(S)-N-(5-Chlorothiophene-2-sulfonyl)-beta,beta-diethylalaninol a Notch-1-sparing gamma-secretase inhibitor.

Abstract：

:Accumulation of beta-amyloid (Abeta), produced by the proteolytic cleavage of amyloid precursor protein (APP) by beta- and gamma-secretase, is widely believed to be associated with Alzheimer's disease (AD). Research around the high-throughput screening hit (S)-4-chlorophenylsulfonyl isoleucinol led to the identification of the Notch-1-sparing (9.5-fold) gamma-secretase inhibitor (S)-N-(5-chlorothiophene-2-sulfonyl)-beta,beta-diethylalaninol 7.b.2 (Abeta(40/42) EC(50)=28 nM), which is efficacious in reduction of Abeta production in vivo.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Cole DC,Stock JR,Kreft AF,Antane M,Aschmies SH,Atchison KP,Casebier DS,Comery TA,Diamantidis G,Ellingboe JW,Harrison BL,Hu Y,Jin M,Kubrak DM,Lu P,Mann CW,Martone RL,Moore WJ,Oganesian A,Riddell DR,Sonnenberg-Reine

doi

10.1016/j.bmcl.2008.11.116

subject

Has Abstract

pub_date

2009-02-01 00:00:00

pages

926-9

issue

3

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(08)01489-3

journal_volume

19

pub_type

杂志文章

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