2-芳基呋喃并[3,2-b]吡啶的合成：C2-芳基取代基对褪黑素活性的影响。
Synthesis of 2-arylfuro[3,2-b]pyridines: Effect of the C2-aryl group on melatoninergic activity.
机构信息
Institut de Chimie Organique et Analytique, Université d'Orléans, UMR CNRS 7311, B.P. 6759, 45067 Orléans Cedex 2, France.
Institut de Recherche Servier, Sciences Expérimentales, 125 Chemin de Ronde, 78290 Croissy, France.
出版信息
Eur J Med Chem. 2016 Feb 15;109:268-75. doi: 10.1016/j.ejmech.2016.01.008. Epub 2016 Jan 12.
We report herein an efficient synthesis of 2-substituted furo[3,2-b]pyridines and their biological evaluation as melatonin receptors ligands. The proposed eight-step sequence ending with a Suzuki coupling allowed a rapid access to various analogues. The steric hindrance and the conformation of the aryl group in C2-position were evaluated regarding the selectivity of the molecule for one of the two high affinity melatonin receptors as well as the activity profile of the compound. Introduction of 1-naphthyl substituent gave the best result in terms of selectivity with a MT1/MT2 ratio of about 150 (MT1 Ki = 198 nM, MT2 Ki = 1.3 nM).
我们在此报告 2-取代呋喃并[3,2-b]吡啶的高效合成及其作为褪黑素受体配体的生物学评价。该方法以 Suzuki 偶联反应为最后一步，经过八步反应可以快速得到各种类似物。通过评估 C2 位芳基的空间位阻和构象，研究了分子对两种高亲和力褪黑素受体之一的选择性以及化合物的活性谱。引入 1-萘基取代基可获得最佳的选择性，MT1/MT2 比值约为 150（MT1 Ki=198 nM，MT2 Ki=1.3 nM）。
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