当前位置： SCI文献检索 > EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Discovery of small molecular (D)-leucinamides as potent, Notch-sparing γ-secretase modulators.

Discovery of small molecular (D)-leucinamides as potent, Notch-sparing γ-secretase modulators.

Abstract：

:Structural optimization of the prior lead 3 led to the small molecular (D)-leucinamides with potent modulating activity and Notch-sparing selectivity on the proteolytic processing of amyloid-β precursor proteins. The N-(R)-epoxypropyl analog 10c exhibited potent γ-secretase modulation compared to DAPT and showed substantial substrate selection for APP cleavage over Notch cleavage, while N-(2-fluoro)benzyl analog 10e showed the most potent γ-secretase inhibition with dull selectivity. The exceptional suppression of ERK-mediated activation suggested that these potent γ-secretase modulators may adapt an alternative pathway to prominently induce the differential inhibition of C99 cleavage by γ-secretase.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Liao YF,Tang YC,Chang MY,Wang BJ,Hu MK

doi

10.1016/j.ejmech.2014.04.006

subject

Has Abstract

pub_date

2014-05-22 00:00:00

pages

143-51

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(14)00325-0

journal_volume

79

pub_type

杂志文章

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