Triazolyl tryptoline derivatives as β-secretase inhibitors

✍ Scribed by Jutamas Jiaranaikulwanitch; Chantana Boonyarat; Valery V. Fokin; Opa Vajragupta

• Book ID: 104004894
• Publisher: Elsevier Science
• Year: 2010
• Tongue: English
• Weight: 967 KB
• Volume: 20
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/j.bmcl.2010.09.043

✦ Synopsis

Tryptoline, a core structure of ochrolifuanine E, which is a hit compound from virtual screening of the Thai herbal database against BACE1 was used as a scaffold for the design of BACE1 inhibitors. The tryptoline was linked with different side chains by 1,2,3-triazole ring readily synthesized by catalytic azide-alkyne cycloaddition reactions. Twenty two triazolyl tryptoline derivatives were synthesized and screened for the inhibitory action against BACE1. JJCA-140 was the most potent inhibitor (IC 50 = 1.49 lM)

and was 100 times more selective for BACE1 than for Cat-D.