2-amino-6-(phenylsulfanyl)-4-(3,4,5-trimethoxyphenyl)-3,5-pyridinedicarbonitrile

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-amino-6-(phenylsulfanyl)-4-(3,4,5-trimethoxyphenyl)-3,5-pyridinedicarbonitrile
• 英文别名: 2-amino-6-(phenylthio)-4-(3,4,5-trimethoxyphenyl)pyridine-3,5-dicarbonitrile；2-Amino-6-phenylsulfanyl-4-(3,4,5-trimethoxyphenyl)pyridine-3,5-dicarbonitrile
• 化学式: C₂₂H₁₈N₄O₃S
• 分子量: 418.476
• InChiKey: FYMUAXHFJSWFBL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  140
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3,4,5-三甲氧基苯甲醛 在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 5.0h， 生成 2-amino-6-(phenylsulfanyl)-4-(3,4,5-trimethoxyphenyl)-3,5-pyridinedicarbonitrile
  参考文献：
  名称：

  合成，体外和计算机筛选2-氨基-4-芳基-6-（苯硫基）吡啶-3,5-二腈作为新型α-葡萄糖苷酶抑制剂。

  摘要：

  抑制α-葡萄糖苷酶对于治疗糖尿病（DM）至关重要。除许多有机支架外，以前已报道吡啶基化合物具有广泛的生物活性。本研究报告了一系列基于吡啶的合成类似物，通过体外，动力学和计算机模拟研究评估了其对α-葡萄糖苷酶抑制的潜力。为此目的，合成了2-氨基-4-芳基-6-（苯硫基）吡啶-3，5-二腈1-28，并进行了体外筛选。与标准阿卡波糖（IC50 = 750±10 µM）相比，包括1-3、7、9、11-14和16在内的几种类似物显示出许多潜在的抑制作用增加。有趣的是，化合物7（IC50 = 55.6±0.3 µM）的抑制强度是标准阿卡波糖的13倍。对最有效分子7的动力学研究揭示了竞争型抑制机制。在计算机上进行了研究以检查配体（化合物7）与α-葡糖苷酶的活性位点残基的结合模式。

  DOI：

  10.1016/j.bioorg.2020.103879

文献信息

• Natural dolomitic limestone-catalyzed synthesis of benzimidazoles, dihydropyrimidinones, and highly substituted pyridines under ultrasound irradiation
  作者：Kumar Godugu、Venkata Divya Sri Yadala、Mohammad Khaja Mohinuddin Pinjari、Trivikram Reddy Gundala、Lakshmi Reddy Sanapareddy、Chinna Gangi Reddy Nallagondu

  DOI：10.3762/bjoc.16.156

  日期：——

  Natural dolomitic limestone (NDL) is employed as a heterogeneous green catalyst for the synthesis of medicinally valuable benzimidazoles, dihydropyrimidinones, and highly functionalized pyridines via C–N, C–C, and C–S bond formations in a mixture of ethanol and H2O under ultrasound irradiation. The catalyst is characterized by XRD, FTIR, Raman spectroscopy, SEM, and EDAX analysis. The main advantages

  天然白云质石灰石（NDL）被用作异质绿色催化剂，用于通过乙醇和H 2的混合物中C–N，C–C和C–S键的形成来合成具有药用价值的苯并咪唑，二氢嘧啶酮和高度官能化的吡啶O在超声波照射下。该催化剂通过XRD，FTIR，拉曼光谱，SEM和EDAX分析来表征。这种方法的主要优点包括广泛的底物范围，更清洁的反应曲线，较短的反应时间和优异的分离产率。该产品不需要色谱纯化，该催化剂可以重复使用七次。因此，与现有报道的催化剂相比，该催化剂是用于合成上述N-杂环的更绿色的替代物。
• K₂CO₃-Mediated, One-Pot, Multicomponent Synthesis of Medicinally Potent Pyridine and Chromeno[2,3-b]pyridine Scaffolds
  作者：Sarita Mishra、Rina Ghosh

  DOI：10.1080/00397911.2011.555284

  日期：2012.8.1

  An efficient one-pot, multicomponent synthesis of 3,5-dicyanopyridines has been developed from the reaction of malononitrile and different thiophenol or thiols with a variety of aldehydes (aromatic including hindered ones, heteroaromatic, and aliphatic) in the presence of 20 mol% of K2CO3 in refluxing 50% aqeuous ethanol. KMnO4 has been utilized as a readily available, inexpensive oxidant for the in situ transformation of the initially formed dihydropyridine intermediate. K2CO3 also mediates the one-pot formation of chromeno[2,3-b]pyridines from reaction of salicylaldehyde or its analogs with malononitrile and thiol or thiophenols. Both of these conditions also work equally well under 50-fold scale-up conditions.Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications (R) to view the free supplemental file.
• One-Step Synthesis of Heterocyclic Privileged Medicinal Scaffolds by a Multicomponent Reaction of Malononitrile with Aldehydes and Thiols
  作者：Nikolai M. Evdokimov、Artem S. Kireev、Andrey A. Yakovenko、Mikhail Yu. Antipin、Igor V. Magedov、Alexander Kornienko

  DOI：10.1021/jo070114u

  日期：2007.4.1

  Heterocyclic privileged medicinal scaffolds involving pyridine, 1,4-dihydropyridine, chromeno[2,3-b]pyridine, and dihydro-1,4-dithiepine frameworks are prepared via a single-step multicomponent reaction of structurally diverse aldehydes with various thiols and malononitrile. Mechanistic studies of the synthetic pathway leading to pyridines reveal that 1,4-dihydropyridines undergo oxidation by the intermediate Knoevenagel adducts rather than by air oxygen. The use of o,o'-disubstituted aromatic aldehydes leads to the corresponding 1,4-dihydropyridines, whereas salicylic aldehydes result in chromeno[2,3-b]pyridines. Reactions of ethanedithiol as a thiol component produce dimeric pyridines with sterically unencumbered aldehydes, while o,o'-disubstituted aromatic aldehydes give dihydro-1,4-dithiepines. Thus, depending on the aldehyde and thiol types, diverse libraries of medicinally relevant compounds can be prepared by a simple one-step process involving no chromatography.
• One-Step, Three-Component Synthesis of Pyridines and 1,4-Dihydropyridines with Manifold Medicinal Utility
  作者：Nikolai M. Evdokimov、Igor V. Magedov、Artem S. Kireev、Alexander Kornienko

  DOI：10.1021/ol052994+

  日期：2006.3.2

  Privileged medicinal scaffolds based on the structures of 2-amino-3,5-dicyano-6-sulfanylpyridines and the corresponding 1,4-dihydropyridines have been prepared via a single-step, three-component reaction of structurally diverse aldehydes with various thiols and malononitrile. Mechanistic studies revealed that 1,4-dyhidropyridines undergo oxidation by the intermediate Knoevenagel adducts rather than by air oxygen. Although the latter process undermines the yields of pyridines, it results in the formation of substituted enaminonitriles, promising antiinflammatory agents.
• Synthesis, in vitro and in silico screening of 2-amino-4-aryl-6-(phenylthio) pyridine-3,5-dicarbonitriles as novel α-glucosidase inhibitors
  作者：Muhammad Ali、Khalid Mohammed Khan、Mohammad Mahdavi、Abdul Jabbar、Shahbaz Shamim、Uzma Salar、Muhammad Taha、Shahnaz Perveen、Bagher Larijani、Mohammad Ali Faramarzi

  DOI：10.1016/j.bioorg.2020.103879

  日期：2020.7

  study reports a series of pyridine based synthetic analogues for their α-glucosidase inhibitory potential assessed by in vitro, kinetics and in silico studies. For this purpose, 2-amino-4-aryl-6-(phenylthio)pyridine-3,5-dicarbonitriles 1-28 were synthesized and subjected to in vitro screening. Several analogs, including 1-3, 7, 9, 11-14, and 16 showed many folds increased inhibitory potential in comparison

  抑制α-葡萄糖苷酶对于治疗糖尿病（DM）至关重要。除许多有机支架外，以前已报道吡啶基化合物具有广泛的生物活性。本研究报告了一系列基于吡啶的合成类似物，通过体外，动力学和计算机模拟研究评估了其对α-葡萄糖苷酶抑制的潜力。为此目的，合成了2-氨基-4-芳基-6-（苯硫基）吡啶-3，5-二腈1-28，并进行了体外筛选。与标准阿卡波糖（IC50 = 750±10 µM）相比，包括1-3、7、9、11-14和16在内的几种类似物显示出许多潜在的抑制作用增加。有趣的是，化合物7（IC50 = 55.6±0.3 µM）的抑制强度是标准阿卡波糖的13倍。对最有效分子7的动力学研究揭示了竞争型抑制机制。在计算机上进行了研究以检查配体（化合物7）与α-葡糖苷酶的活性位点残基的结合模式。