A new class of ghrelin O-acyltransferase inhibitors incorporating triazole-linked lipid mimetic groups
摘要:
Inhibitors of ghrelin O-acyltransferase (GOAT) have untapped potential as therapeutics targeting obesity and diabetes. We report the first examples of GOAT inhibitors incorporating a triazole linkage as a biostable isosteric replacement for the ester bond in ghrelin and amide bonds in previously reported GOAT inhibitors. These triazole-containing inhibitors exhibit sub-micromolar inhibition of the human isoform of GOAT (hGOAT), and provide a foundation for rapid future chemical diversification and optimization of hGOAT inhibitors. (C) 2015 Elsevier Ltd. All rights reserved.
A new class of ghrelin O-acyltransferase inhibitors incorporating triazole-linked lipid mimetic groups
作者:Feifei Zhao、Joseph E. Darling、Richard A. Gibbs、James L. Hougland
DOI:10.1016/j.bmcl.2015.05.009
日期:2015.7
Inhibitors of ghrelin O-acyltransferase (GOAT) have untapped potential as therapeutics targeting obesity and diabetes. We report the first examples of GOAT inhibitors incorporating a triazole linkage as a biostable isosteric replacement for the ester bond in ghrelin and amide bonds in previously reported GOAT inhibitors. These triazole-containing inhibitors exhibit sub-micromolar inhibition of the human isoform of GOAT (hGOAT), and provide a foundation for rapid future chemical diversification and optimization of hGOAT inhibitors. (C) 2015 Elsevier Ltd. All rights reserved.
Site‐selective Hydrogenation/Deuteration of Benzylic Olefins Enabled by Electroreduction Using Water
作者:Simon Kolb、Daniel B. Werz
DOI:10.1002/chem.202300849
日期:——
Electroreduction of benzylicolefins has been applied to site-selectively hydrogenate such double bonds while other functions that react under regular hydrogenation conditions are present. By the use of water as proton source this protocol also allows deuteration by simply switching to D2O. The applicability of this method was shown by the use of a commercially available electrolysis setup and a broad
苄基烯烃的电还原已应用于位点选择性氢化此类双键,同时存在在常规氢化条件下反应的其他功能。通过使用水作为质子源,该协议还允许通过简单地切换到 D 2 O 进行氘化。该方法的适用性通过使用商用电解装置和广泛的底物范围得到证明。