Department of Chemistry, Faculty of Science, Cairo University, Giza, Eritrea.
Department of Pharmaceutical Chemistry, College of Pharmacy, University of Hail, Hail, Kingdom of Saudi Arabia.
Anticancer Agents Med Chem. 2018 Feb 7;17(14):1951-1962. doi: 10.2174/1871520617666170725153523.
Among a wide range of pyridines, 3-cyanopyridines acquired a special attention due to their wide range of pharmacological activities especially the therapeutic activities. Many pharmacological drugs containing the pyridine nucleus were known in the market.
The aim of this work was to synthesize target molecules not only possess anti-tumor activities but also kinase inhibitors. To achieve this goal, our strategy was to synthesize a series of 3-cyanopyridine derivatives using 2-aminoprop-1-ene-1,1,3-tricarbonitrile (1) as the key starting material for many heterocyclization reactions.
Muticoponent reactions were adopted using compound 1 to get different pyridine derivatives that were capable for different heterocyclization reactions.
Antiproliferative evaluations and c-Met kinase, Pim-1 kinse inhibitions were perform where some compounds gave high activities.
Compounds that showed high antiprolifeative activity were tested gor c-Met-independent and the results showed that compounds 5c, 5e, 5f, 7c, 7f and 16d were more active than foretinib. The Pim-1 kinase inhibition activity of some selected compounds showed that compounds 5e and 16c were high potent to inhibit Pim-1 activity.
在广泛的吡啶类化合物中，3-氰基吡啶因其广泛的药理活性，尤其是治疗活性，而受到特别关注。许多含有吡啶核的药物在市场上已经被发现。
本工作的目的是合成不仅具有抗肿瘤活性而且还具有激酶抑制剂活性的靶分子。为了实现这一目标，我们的策略是使用 2-氨基丙-1-烯-1,1,3-三腈（1）作为许多杂环化反应的关键起始原料，合成一系列 3-氰基吡啶衍生物。
采用多组分反应，使用化合物 1 得到不同的吡啶衍生物，这些衍生物能够进行不同的杂环化反应。
进行了抗增殖评估和 c-Met 激酶、Pim-1 激酶抑制实验，其中一些化合物表现出了较高的活性。
显示出高抗增殖活性的化合物被测试了对 c-Met 的依赖性，结果表明化合物 5c、5e、5f、7c、7f 和 16d 比 foretinib 更具活性。一些选定化合物的 Pim-1 激酶抑制活性表明，化合物 5e 和 16c 对抑制 Pim-1 活性具有高潜力。
