6-amino-4-(4-chlorophenyl)-2-thioxo-1,2-dihydropyridine-3,5-dicarbonitrile | 110691-02-6

• 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: 6-amino-4-(4-chlorophenyl)-2-thioxo-1,2-dihydropyridine-3,5-dicarbonitrile
• 英文别名: 2-amino-4-(4-chlorophenyl)-6-sulfanylidene-1H-pyridine-3,5-dicarbonitrile
• CAS: 110691-02-6
• 化学式: C₁₃H₇ClN₄S
• 分子量: 286.744
• InChiKey: UVNAKEUHQWSNFY-UHFFFAOYSA-N

物化性质

• 熔点：
  266-267 °C(Solv: ethanol (64-17-5))
• 沸点：
  374.1±52.0 °C(Predicted)
• 密度：
  1.52±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  118
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-amino-4-(4-chlorophenyl)-2-thioxo-1,2-dihydropyridine-3,5-dicarbonitrile 、 alkaline earth salt of/the/ methylsulfuric acid 在 氢氧化钾 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.02h， 生成 2-amino-4-(4-chlorophenyl)-6-(2-(3-(2,4-dichlorophenyl)isoxazol-5-yl)-2-oxoethylthio)pyridine-3,5-dicarbonitrile
  参考文献：
  名称：

  基于2-氨基吡啶-3,5-二甲腈的化合物抑制病毒的构效关系研究：平行合成，生物活性和体外药代动力学。

  摘要：

  2-氨基吡啶-3,5-二甲腈化合物以前被鉴定为显性负病毒蛋白突变体的模拟物，并抑制病毒在培养细胞中的复制。在这里，我们报告从6-氨基吡啶-3,5-二甲腈支架的全面的结构-活性关系研究中发现的结果。我们确定了具有明显改善的生物活性（约40倍）的抗感染性ion病毒同工型（PrPSc）复制和合适的药代动力学特征的化合物，以保证在病毒疾病的动物模型中进行评估。

  DOI：

  10.1021/jm061045z
• 作为产物：
  描述：

  2,6-二氨基-4-(4-氯苯基)-4H-硫代吡喃-3,5-二甲腈 在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 5.0h， 生成 6-amino-4-(4-chlorophenyl)-2-thioxo-1,2-dihydropyridine-3,5-dicarbonitrile
  参考文献：
  名称：

  Atalla; Hussein; Badr, Revue Roumaine de Chimie, 1998, vol. 43, # 2, p. 163 - 170

  摘要：

  DOI：

文献信息

• Amino-3,5-Dicyanopyridines Targeting the Adenosine Receptors. Ranging from Pan Ligands to Combined A1/A2B Partial Agonists
  作者：Daniela Catarzi、Flavia Varano、Katia Varani、Fabrizio Vincenzi、Silvia Pasquini、Diego Dal Ben、Rosaria Volpini、Vittoria Colotta

  DOI：10.3390/ph12040159

  日期：——

  The amino-3,5-dicyanopyridine derivatives belong to an intriguing series of adenosine receptor (AR) ligands that has been developed by both academic researchers and industry. Indeed, the studies carried out to date underline the versatility of the dicyanopyridine scaffold to obtain AR ligands with not only a wide range of affinities but also with diverse degrees of efficacies at the different ARs. These observations prompted us to investigate on the structure–activity relationships (SARs) of this series leading to important previously reported results. The present SAR study has helped to confirm the 1H-imidazol-2-yl group at R2 position as an important feature for producing potent AR agonists. Moreover, the nature of the R1 substituent highly affects not only affinity/activity at the hA1 and hA2B ARs but also selectivity versus the other subtypes. Potent hA1 and hA2B AR ligands were developed, and among them, the 2-amino-6-[(1H-imidazol-2-ylmethyl)sulfanyl]-4-[4-(prop-2-en-1-yloxy)phenyl]pyridine-3,5-dicarbonitrile (3) is active in the low nanomolar range at these subtypes and shows a good trend of selectivity versus both the hA2A and hA3 ARs. This combined hA1/hA2B partial agonist activity leads to a synergistic effect on glucose homeostasis and could potentially be beneficial in treating diabetes and related complications.

  氨基-3,5-二氰吡啶衍生物属于一个引人注目的腺苷受体（AR）配体系列，这个系列是由学术研究人员和工业界共同开发的。事实上，迄今为止进行的研究强调了二氰吡啶骨架的多功能性，可以获得不仅具有广泛亲和力而且在不同AR上具有不同效力的AR配体。这些观察结果促使我们对这个系列的结构-活性关系（SARs）进行研究，从而得到了重要的先前报道的结果。当前的SAR研究有助于确认R2位置的1H-咪唑-2-基团是产生有效AR激动剂的重要特征。此外，R1取代基的性质不仅高度影响对hA1和hA2B AR的亲和力/活性，还影响对其他亚型的选择性。开发了有效的hA1和hA2B AR配体，其中2-氨基-6-[(1H-咪唑-2-基甲基)硫基]-4-[4-(丙-2-烯-1-氧基)苯基]吡啶-3,5-二腈（3）在这些亚型中的活性处于低纳摩尔范围，并显示出对hA2A和hA3 AR的良好选择性趋势。这种结合的hA1/hA2B部分激动剂活性对葡萄糖稳态产生协同效应，可能有助于治疗糖尿病及相关并发症。
• Mannich reaction in the synthesis of N,S-containing heterocycles. 16.*Synthesis of derivatives of tetra-hydropyrido[1,2-a][1,3,5]triazine and 5,6,12,13-tetra-hydro-1H,8H-dipyrido[1,2-a:1',2'-e][1,3,5,7]tetrazocine
  作者：V. V. Dotsenko、S. Yu. Suikov、T. M. Pekhtereva、S. G. Krivokolysko

  DOI：10.1007/s10593-013-1339-5

  日期：2013.10

  aromatic amines were used 3,10-diaryl-1,8-dithioxo-5,6,12,13-tetrahydro-1H,8H-dipyrido[1,2-a:1′,2′-e][1,3,5,7]tetrazocine-2,4,9,11-tetracarbonitriles or their mixtures with the above-mentioned pyrido[1,2-a][1,3,5]triazines were obtained. Dipyrido[1,2-a:1′2′-e]-[1,3,5,7]tetrazocine derivatives were also synthesized by direct condensation of 6-amino-4-aryl-2-thioxo-1,2-dihydro-pyridine-3,5-dicarbonitriles

  在碱催化条件下，研究了伯胺和过量甲醛作用下6-氨基-4-芳基-2-硫代-2-1,2-二氢吡啶-3,5-二腈的氨基甲基化。发现产物的结构和产率在很大程度上取决于起始胺的结构，还取决于试剂的比例和反应条件。在烷基或芳基烷基胺的情况下，8-芳基-3-烷基（芳基烷基）-6-thioxo-1,3,4,6-四氢-2 H-吡啶[1,2- a ] [1,3， 5]制得了三嗪-7,9-二腈，而当使用芳香胺时，则使用了3,10-二芳基-1,8-二硫代-5,6,12,13-四氢-1 H，8 H-双吡啶[1， 2- a：1′，2′- e获得了[[1,3,5,7]四唑啉-2,4,9,11-四腈或它们与上述吡啶并[1,2- a ] [1,3,5]三嗪的混合物。双吡啶[1,2- a：1'2'- e ]-[1,3,5,7]四唑啉衍生物也通过6-氨基-4-芳基-2-硫代-1,2-直接缩合而合成。二氢吡啶-3,5-二腈与甲醛。
• 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
• Pyrolysis and photolysis processes of pyran and thiopyran derivatives
  作者：A. A. Atalla、A. M. Hussein、M. Z. A. Badr

  DOI：10.1007/bf00807636

  日期：1997.1

  Pyrolysis and photolysis of 2-amino-3,5-dicyano-6-phenyl-4H-pyran (1) afford HNCO, acrylonitrile, cinnamonitrile, and 2-hydroxy-3,5-dicyano-6-phenylpyridine. Pyrolysis of 2-carboxyimino-3,5-dicyano-6-phenyI-4H-pyran (2) gives HCN, acrylonitrile, cinnamonitrile and 2-hydroxy-3,5-dicyano-6-phenylpyridine. Furthermore, both pyrolysis and photolysis of 2,6-diamino-3,5-dicyanothiopyran (3a) gives rise to HNCS, acrylonitrile and 6-amino-3,5-dicyano-6-mercaptopyridin, Moreover, comparative studies of pyrolysis and photolysis of 2,6-dicyano-4-arylthiopyran derivatives 3b-d revealed similar results. The similarity of products obtained from pyrolysis and photolysis and the mechanistic implications of these data are discussed.
• Cascade Synthesis of Thieno[2,3-<i>b</i>]pyridines by Using Intramolecular Cyclization Reactions of 3-Cyano-2-(organylmethylthio)pyridines
  作者：Fatemeh Alinaghizadeh、Mahboobeh Zahedifar、Mohammad Seifi、Hassan Sheibani

  DOI：10.5935/0103-5053.20150309

  日期：——

  2-Amino-4-aryl-6-mercaptopyridine-3,5-dicarbonitriles as starting materials have been prepared by reducing of 2-amino-4-aryl-6-(phenylthio)pyridine-3,5-dicarbonitrile derivatives which were synthesized on stepwise one-pot three component reaction of malononitrile, aldehydes and thiophenol in the presence of base catalysts such as triethylamine, high surface area (HSA) MgO or nanocrystalline magnesium oxide. Alkylation of 2-amino-4-aryl-6- mercaptopyridine-3,5-dicarbonitriles with alpha-halogen compounds in presence of sodium alkoxide as base catalyst followed with cyclization afforded thethieno[2,3-b]pyridine derivatives in excellent yields and in a short reaction time.