2-amino-4-(3-hydroxyphenyl)-6-(phenylthio)pyridine-3,5-dicarbonitrile | 735273-34-4

• 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-4-(3-hydroxyphenyl)-6-(phenylthio)pyridine-3,5-dicarbonitrile
• 英文别名: 2-Amino-4-(3-hydroxyphenyl)-6-phenylsulfanylpyridine-3,5-dicarbonitrile
• CAS: 735273-34-4
• 化学式: C₁₉H₁₂N₄OS
• 分子量: 344.396
• InChiKey: OVPQQXGTXSGOBV-UHFFFAOYSA-N

物化性质

• 沸点：
  654.6±55.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  132
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-amino-4-(3-hydroxyphenyl)-6-(phenylthio)pyridine-3,5-dicarbonitrile 在 sodium sulfide 、 碳酸氢钠 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 LUF5835
  参考文献：
  名称：

  New, Non-Adenosine, High-Potency Agonists for the Human Adenosine A_2B Receptor with an Improved Selectivity Profile Compared to the Reference Agonist N-Ethylcarboxamidoadenosine

  摘要：

  The adenosine A(2B) receptor is the least well characterized of the four known adenosine receptor subtypes because of the absence of potent, selective agonists. Here, we present five non-adenosine agonists. Among them, 2-amino-4-(4-hydroxyphenyl)-6-(1H-imidazol-2-ylmethylsulfanyl)pyridine-3,5.-dicarbonitrile, 17, LUF5834, is a high-efficacy partial agonist with EC50 = 12 nM and 45-fold selectivity over the adenosine A(3) receptor but lacking selectivity versus the A, and A(2A) subtypes. Compound 18, LUF5835, the 3-hydroxyphenyl analogue, is a full agonist with EC50 = 10 nM.

  DOI：

  10.1021/jm049947s
• 作为产物：
  描述：

  间羟基苯甲醛 在 哌啶 、 三乙胺 作用下， 以 乙醇 为溶剂， 反应 7.0h， 生成 2-amino-4-(3-hydroxyphenyl)-6-(phenylthio)pyridine-3,5-dicarbonitrile
  参考文献：
  名称：

  发现高效腺苷 A1 受体激动剂：靶向正电子发射断层扫描探针

  摘要：

  用于正电子发射断层扫描 (PET) 的腺苷受体 (AR) 放射性示踪剂提供了关于AR 在中枢神经系统 (CNS)中的体内生物分布的知识，这对各种神经精神疾病具有治疗意义。此外，仍然缺乏能够成像不同生理和病理条件下内源性腺苷水平变化的放射性配体。在啮齿动物 PET 研究中，已知拮抗剂腺苷 A 1受体 (A 1 R) 放射性示踪剂 [ 11 C]MDPX 的结合未能被升高的内源性腺苷抑制。由于大多数已知的 AR PET 放射性示踪剂都是拮抗剂，我们建议 A 1R 激动剂放射性配体可能对测量内源性腺苷浓度的变化具有更高的灵敏度。在此，我们报告了我们在开发用于 PET 的完全激动剂腺苷 A 1放射性配体方面的最新发现。基于 3,5-二氰基吡啶模板，设计和合成了 16 种新衍生物以优化结合亲和力和功能活性，从而产生了两种具有单位数纳摩尔亲和力和良好亚型选择性的完全激动剂（化合物27和29 ）（A 1

  DOI：

  10.1021/acschemneuro.1c00397

文献信息

• 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。
• Wang resin catalyzed sonochemical synthesis of 2-amino-3,5-dicarbonitrile-6-thio-pyridines as potential inhibitors of SIRT1
  作者：Hemalatha Kotakommula、Vaishnavi Chintala、Satya Sree Nannapaneni、Naresh Kumar Katari、Ravikumar Kapavarapu、Manojit Pal

  DOI：10.1016/j.molstruc.2023.136756

  日期：2024.1

  these molecules was established via the 3-component reaction (3-CR) of appropriate aliphatic or (hetero)aromatic aldehyde, malononitrile and thiophenol under ultrasound. The reaction was catalyzed by the sulphonic acid-functionalized Wang resin (Wang-OSO3H) and proceeded in aqueous media under open air for 1 h to afford the desired products in 65-86% yields. The recoverability and recyclability of the

  对识别潜在抗癌药物的新方法/策略的探索促使我们关注 SIRT1，它被认为是一种新兴的癌症药理学靶点。选择 2-氨基-3,5-二甲腈-6-硫代-吡啶作为设计新的和可能的 SIRT1 抑制剂的框架。首先，在计算机上基于该框架的许多分子的对接不仅显示了它们与 SIRT1 的良好相互作用，而且表明了它们相对于 SIRT2 对该蛋白的潜在选择性。该研究还表明 VAL412、PHE414、ILE347、ALA262、ILE411、HIS363、GLN345、ASN346、ILE270、ILE316、PHE273 和 PHE297 是这些分子的常见相互作用残基，其中 VAL412 和 PHE414 主要参与氢键相互作用。通过适当的脂肪族或（杂）芳香族醛、丙二腈和苯硫酚在超声波下的三组分反应（3-CR），可以方便地获取这些分子。该反应由磺酸功能化的 Wang 树脂 (Wang-OSO 3H)并在露天的水性
• 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.
• CuI nanoparticles: a highly active and easily recyclable catalyst for the synthesis of 2-amino-3,5-dicyano-6-sulfanyl pyridines
  作者：Javad Safaei-Ghomi、Mohammad Ali Ghasemzadeh

  DOI：10.1080/17415993.2012.728220

  日期：2013.6.1

  CuI nanoparticles as a worthwhile and reusable catalyst supply an eco-friendly procedure for the synthesis of 2-amino-3,5-dicyano-6-sulfanyl pyridine derivatives. The products were obtained in high yields and short reaction times via multicomponent reaction of aldehydes, malononitrile and thiols under reflux conditions. The method presented is mild, efficient, inexpensive and satisfactory to give the products in the presence of novel nanoscale materials.
• WEB (water extract of banana): An efficient natural base for one-pot multi-component synthesis of 2-amino-3,5-dicarbonitrile-6-thio-pyridines
  作者：Alireza Allahi、Batool Akhlaghinia

  DOI：10.1080/10426507.2020.1835905

  日期：2021.3.4

  One-pot multi-component synthesis of 2-amino-3,5-dicarbonitrile-6-thio-pyridines derivatives using WEB (water extract of banana peels ash) as a green catalyst is described. A variety of aromatic aldehydes (with electron-donating and electron-withdrawing groups) in conjunction with aromatic and aliphatic thiols are known to tolerate this reaction condition using WEB. The reaction has simple work up procedure without using toxic solvents.