Discovery of potent beta-secretase (bace-1) inhibitors by the synthesis of isophthalamide-containing hybrids.

ABSTRACT:

Aim

The aim of this study was to design and synthesize a series of high activity compounds against aspartyl protease beta-secretase (BACE-1) bearing hydroxyethylene (HE) framework.

Methods

First, we designed the small library based on our previous work and rational analysis. Subsequently, thirteen compounds were selected and synthesized using skilled solid phase synthetic methods to explore the relationship between structure and activity. We then used molecular modeling to explain the possible binding mode.

Results

Thirteen new compounds (6-18) have been designed, synthesized and bioassayed. Their structures were determined by nuclear magnetic resonance (NMR) spectra, low- and high-resolution mass spectra and optical rotation. Most compounds have shown moderate to exc

SUBMITTER: Zhu YP 

PROVIDER: S-EPMC4002469 | biostudies-literature | 2009 Feb

REPOSITORIES: biostudies-literature