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

YF Liao, YC Tang, MY Chang, BJ Wang…

Index: Liao, Yung-Feng; Tang, Yu-Cheng; Chang, Ming-Yun; Wang, Bo-Jeng; Hu, Ming-Kuan European Journal of Medicinal Chemistry, 2014 , vol. 79, p. 143 - 151

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Citation Number: 3

Abstract

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 ...