Base-Mediated Syntheses of Di- and Trisubstituted Imidazoles from Amidine Hydrochlorides and Bromoacetylenes
作者:Xiao Yun Chen、Ulli Englert、Carsten Bolm
DOI:10.1002/chem.201502707
日期:2015.9.14
A new transition metal‐free method for the preparation of substituted imidazoles from easy‐to‐handle amidinehydrochlorides and bromoacetylenes has been developed. The reactions proceed in air and use inexpensive K2CO3 as base. Additions of 2,2′‐bipyridine and water have beneficial effects on the product yields. Various di‐ and trisubstituted imidazoles have been prepared in good yields (up to 88 %)
已开发出一种新的无过渡金属的方法,该方法由易于处理的am盐酸盐和溴乙炔制备取代的咪唑。反应在空气中进行,并使用廉价的K 2 CO 3作为碱。添加2,2'-联吡啶和水对产品收率有有利影响。各种二,三取代的咪唑均以高收率(高达88%)制备。
Identification and characterization of diarylimidazoles as hybrid inhibitors of butyrylcholinesterase and amyloid beta fibril formation
In this contribution, a chemical collection of aromatic compounds was screened for inhibition on butyrylcholinesterase (BChE)'s hydrolase activity using Ellman's reaction. A set of diarylimidazoles was identified as highly selective inhibitors of BChE hydrolase activity and amyloid beta (A beta) fibril formation. New derivatives were synthesized resulting in several additional hits, from which the most active was 6c, 4-(3-ethylthiophenyl)-2-(3-thieny1)-1H-imidazole, an uncompetitive inhibitor of BChE hydrolase activity (IC50 BChE = 0.10 mu M; K-i = 0.073 +/- 0.011 mu M) acting also on Ap fibril formation (IC50 = 5.8 mu M). With the aid of structure-activity relationship (SAR) studies, chemical motifs influencing the BChE inhibitory activity of these imidazoles were proposed. These bifunctional inhibitors represent good tools in basic studies of BChE and/or promising lead molecules for AD therapy. (C) 2011 Elsevier B.V. All rights reserved.