6-amino-4-(4-methylphenyl)-2-thioxo-1,2-dihydropyridine-3,5-dicarbonitrile | 333781-43-4

• 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: 6-amino-4-(4-methylphenyl)-2-thioxo-1,2-dihydropyridine-3,5-dicarbonitrile
• 英文别名: 2-amino-4-(4-methylphenyl)-6-sulfanylidene-1H-pyridine-3,5-dicarbonitrile
• CAS: 333781-43-4
• 化学式: C₁₄H₁₀N₄S
• 分子量: 266.326
• InChiKey: IWLCKOYPEPDLBD-UHFFFAOYSA-N

物化性质

• 沸点：
  365.6±52.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 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-methylphenyl)-2-thioxo-1,2-dihydropyridine-3,5-dicarbonitrile 、 2-溴乙醇 在 碳酸氢钠 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以81%的产率得到2-Amino-6-(2-hydroxy-ethylsulfanyl)-4-p-tolyl-pyridine-3,5-dicarbonitrile
  参考文献：
  名称：

  A Series of Ligands Displaying a Remarkable Agonistic−Antagonistic Profile at the Adenosine A₁ Receptor

  摘要：

  Adenosine receptor agonists are usually variations of the natural ligand, adenosine. The ribose moiety in the ligand has previously been shown to be of great importance for the agonistic effects of the compound. In this paper, we present a series of nonadenosine ligands selective for the adenosine A(1) receptor with an extraordinary pharmacological profile. 2-Amino-4-benzo[1,3]dioxol-5-yl-6-(2-hydroxyethylsulfanyl)pyridine-3,5-dicarbonitrile (70, LUF 5853) shows full agonistic behavior comparable with the reference compound CPA, while also displaying comparable receptor binding affinity (K-i = 11 nM). In contrast, compound 58 (2-amino-4-(3-trifluoromethylphenyl)-6-(2-hydroxyethylsulfanyl)pyridine-3,5-dicarbonitrile, LUF 5948) has a binding affinity of 14 nM and acts as an inverse agonist. Also present within this same series are compounds that show neutral antagonism of the adenosine A(1) receptor, for example compound 65 (2-amino-4-(4-difluoromethoxyphenyl)-6-(2-hydroxyethylsulfanyl)pyridine-3,5-dicarbonitrile, LUF 5826).

  DOI：

  10.1021/jm049597+
• 作为产物：
  描述：

  对甲基苯甲醛 在 sodium sulfide 、 aluminum oxide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 6-amino-4-(4-methylphenyl)-2-thioxo-1,2-dihydropyridine-3,5-dicarbonitrile
  参考文献：
  名称：

  Amino-3,5-Dicyanopyridines Targeting the Adenosine Receptors. Ranging from Pan Ligands to Combined A1/A2B Partial Agonists

  摘要：

  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。

  DOI：

  10.3390/ph12040159

文献信息

• Structure−Activity Relationship Study of Prion Inhibition by 2-Aminopyridine-3,5-dicarbonitrile-Based Compounds:  Parallel Synthesis, Bioactivity, and in Vitro Pharmacokinetics
  作者：Barnaby C. H. May、Julie A. Zorn、Juanita Witkop、John Sherrill、Andrew C. Wallace、Giuseppe Legname、Stanley B. Prusiner、Fred E. Cohen

  DOI：10.1021/jm061045z

  日期：2007.1.1

  2-Aminopyridine-3,5-dicarbonitrile compounds were previously identified as mimetics of dominant-negative prion protein mutants and inhibit prion replication in cultured cells. Here, we report findings from a comprehensive structure-activity relationship study of the 6-aminopyridine-3,5-dicarbonitrile scaffold. We identify compounds with significantly improved bioactivity (approximately 40-fold) against

  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。
• 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。
• 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.
• US7504421B2
  申请人：——

  公开号：US7504421B2

  公开（公告）日：2009-03-17
• A Series of Ligands Displaying a Remarkable Agonistic−Antagonistic Profile at the Adenosine A₁ Receptor
  作者：Lisa C. W. Chang、Jacobien K. von Frijtag Drabbe Künzel、Thea Mulder-Krieger、Ronald F. Spanjersberg、Sophie F. Roerink、Gijs van den Hout、Margot W. Beukers、Johannes Brussee、Adriaan P. IJzerman

  DOI：10.1021/jm049597+

  日期：2005.3.1

  Adenosine receptor agonists are usually variations of the natural ligand, adenosine. The ribose moiety in the ligand has previously been shown to be of great importance for the agonistic effects of the compound. In this paper, we present a series of nonadenosine ligands selective for the adenosine A(1) receptor with an extraordinary pharmacological profile. 2-Amino-4-benzo[1,3]dioxol-5-yl-6-(2-hydroxyethylsulfanyl)pyridine-3,5-dicarbonitrile (70, LUF 5853) shows full agonistic behavior comparable with the reference compound CPA, while also displaying comparable receptor binding affinity (K-i = 11 nM). In contrast, compound 58 (2-amino-4-(3-trifluoromethylphenyl)-6-(2-hydroxyethylsulfanyl)pyridine-3,5-dicarbonitrile, LUF 5948) has a binding affinity of 14 nM and acts as an inverse agonist. Also present within this same series are compounds that show neutral antagonism of the adenosine A(1) receptor, for example compound 65 (2-amino-4-(4-difluoromethoxyphenyl)-6-(2-hydroxyethylsulfanyl)pyridine-3,5-dicarbonitrile, LUF 5826).