Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.
J Org Chem. 2022 Mar 18;87(6):3922-3933. doi: 10.1021/acs.joc.1c02237. Epub 2022 Feb 28.
A series of tricyclic and polycyclic pyrido[1,2-]purine derivatives were designed and synthesized via a two-step, one-pot reaction of 2,4-dichloro-5-amino-6-methylpyrimidine with pyridine under reflux conditions. Various derivatives of pyrido[1,2-]purine were also synthesized by substituting the chlorine atom with secondary amines. After careful physiochemical and pharmacokinetic predictions, the inhibitory effects of the synthesized compounds against the main protease of SARS-CoV-2 have been evaluated by molecular docking and molecular dynamics approaches. The in silico results revealed that among all of the studied compounds, the morpholine/piperidine-substituted pyrido[1,2-]purine derivatives are the best candidates as effective inhibitors of SARS-CoV-2.
设计并合成了一系列三环和多环吡啶并[1,2-]嘌呤衍生物，通过 2,4-二氯-5-氨基-6-甲基嘧啶与吡啶在回流条件下的两步一锅反应得到。还通过用仲胺取代氯原子来合成吡啶并[1,2-]嘌呤的各种衍生物。在进行了仔细的物理化学和药代动力学预测后，通过分子对接和分子动力学方法评估了合成化合物对 SARS-CoV-2 主要蛋白酶的抑制作用。计算结果表明，在所研究的所有化合物中，吗啡啉/哌啶取代的吡啶并[1,2-]嘌呤衍生物是作为 SARS-CoV-2 有效抑制剂的最佳候选物。
