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首页> 外文期刊>European Journal of Medicinal Chemistry: Chimie Therapeutique >Facile synthesis, vasorelaxant properties and molecular modeling studies of 2-amino-8a-methoxy-4H-pyrano(3,2-c)pyridine-3-carbonitriles.
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Facile synthesis, vasorelaxant properties and molecular modeling studies of 2-amino-8a-methoxy-4H-pyrano(3,2-c)pyridine-3-carbonitriles.

机译：2-氨基-8a-甲氧基-4H-吡喃并（3,2-c）吡啶-3-甲腈的简便合成，血管舒张性质和分子模型研究。

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摘要

A facile synthetic approach towards 6-alkyl-2-amino-4-aryl-4a,5,6,7,8,8a-hexahydro-8a-methoxy-4H-pyrano[3,2-c]pyridin e-3-carbonitriles 3a-n was reported via reaction of 1-alkyl-4-piperidones 1a,b with ylidenemalononitriles 2a-h in methanol in the presence of sufficient amount of sodium. The structure of 3 was established through different spectroscopic techniques and confirmed by single crystal X-ray studies. Vasodilation activities of the synthesized compounds were investigated in vitro using isolated thoracic aortic rings of Wister rats pre-contracted with norepinephrine hydrochloride standard method. All the prepared analogues exhibited considerable vasodilation properties especially, 3g and 3c which revealed the best vasodilation potency (IC50=0.30, 0.37 mM, respectively) among all the tested compounds. Molecular modeling studies, including fitting of the synthesized compounds to a 3D-pharmacophore and their docking into optimized homology model as alpha1-AR antagonists showed high docking score and fit values. The experimental vasodilation activities of compounds 3a-n are consistent with their molecular modeling results.
机译：一种简便的合成方法，可用于6-烷基-2-氨基-4-芳基-4a，5,6,7,8,8a-六氢-8a-甲氧基-4H-吡喃并[3,2-c]吡啶e-3-通过1-烷基-4-哌啶酮1a，b与亚甲基丙二腈2a-h在甲醇中在足够量的钠存在下的反应报道了腈3a-n。 3的结构是通过不同的光谱技术确定的，并通过单晶X射线研究得到证实。使用盐酸去甲肾上腺素标准方法预收缩的Wister大鼠的离体胸主动脉环，体外研究了合成化合物的血管舒张活性。所有制备的类似物均表现出相当大的血管舒张特性，尤其是3g和3c，它们在所有受试化合物中均显示出最佳的血管舒张功效（分别为IC50 = 0.30、0.37 mM）。分子建模研究（包括将合成的化合物拟合至3D药效团并将其对接为alpha1-AR拮抗剂的优化同源性模型）显示出较高的对接分数和拟合值。化合物3a-n的实验性血管舒张活性与其分子模拟结果一致。

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