Novel phenyl(thio)ureas bearing (thio)oxothiazoline group as potential BACE-1 inhibitors: synthesis and biological evaluation

作者：Andreoli Federico; Doukara Abdallah Larbi; Mehdid Mohammed Amine; Vanthuyne Nicolas; Roussel Christian; Dessolin Jean; Kraus Jean Louis^*

来源：Journal of Enzyme Inhibition and Medicinal Chemistry, 2013, 28(1): 153-162.

DOI：10.3109/14756366.2011.642375

• BACE-1
• N-aryl-thiazoline-2-(thi)ones
• ureas
• thioureas
• Alzheimer disease

We report the synthesis and the beta-site amyloid precursor protein cleaving enzyme-1 inhibitory properties of novel phenyl(thio) ureas bearing 2-(thio)oxothiazoline derivatives. A library of analogues was prepared according to specific synthetic schemes and the inhibitory activity was monitored using a fluorescence resonance energy transfer assay. Several analogues show potent inhibitory activities ranging between 1 and 0.01 mu M and the activity is related to the NH acidity of the (thio) urea motif. Our results illustrate once again the close relationship between molecular recognition, complexation of the active site in enzymatic system, and organocatalysis utilizing explicit hydrogen bonding.

• 出版日期2013-2