6-amino-4-(2-methoxyphenyl)-2-thioxo-1,2-dihydropyridine-3,5-dicarbonitrile | 202405-79-6

• 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-(2-methoxyphenyl)-2-thioxo-1,2-dihydropyridine-3,5-dicarbonitrile
• 英文别名: 2-amino-4-(2-methoxyphenyl)-6-sulfanylidene-1H-pyridine-3,5-dicarbonitrile
• CAS: 202405-79-6
• 化学式: C₁₄H₁₀N₄OS
• 分子量: 282.326
• InChiKey: CDVAJLNDUGZHDJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  127
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-amino-4-(2-methoxyphenyl)-2-thioxo-1,2-dihydropyridine-3,5-dicarbonitrile 在 氢氧化钾 、 碘 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以91%的产率得到bis[6-amino-3,5-dicyano-4-(2-methoxyphenyl)-2-pyridinyl] disulfide
  参考文献：
  名称：

  通过4-芳基-2,6-二氨基-4H-硫吡喃环化合成6-氨基-4-芳基-3,5-二氰基-3,4-二氢吡啶-2（1H）-硫酮的新方法

  摘要：

  DOI：

  10.1007/bf02253028
• 作为产物：
  描述：

  6-Amino-4-(2-methoxy-phenyl)-2-thioxo-1,2,3,4-tetrahydro-pyridine-3,5-dicarbonitrile 在 溶剂黄146 作用下， 以72%的产率得到6-amino-4-(2-methoxyphenyl)-2-thioxo-1,2-dihydropyridine-3,5-dicarbonitrile
  参考文献：
  名称：

  通过4-芳基-2,6-二氨基-4H-硫吡喃环化合成6-氨基-4-芳基-3,5-二氰基-3,4-二氢吡啶-2（1H）-硫酮的新方法

  摘要：

  DOI：

  10.1007/bf02253028

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。
• 3,6-Diamino-4-(2-halophenyl)-2-benzoylthieno[2,3-<i>b</i>]pyridine-5-carbonitriles Are Selective Inhibitors of Plasmodium falciparum Glycogen Synthase Kinase-3
  作者：Wiebke Fugel、Anselm Erich Oberholzer、Bernhard Gschloessl、Ron Dzikowski、Narkiss Pressburger、Lutz Preu、Laurence H. Pearl、Blandine Baratte、Morgane Ratin、Ilya Okun、Christian Doerig、Sebastian Kruggel、Thomas Lemcke、Laurent Meijer、Conrad Kunick

  DOI：10.1021/jm301575n

  日期：2013.1.10

  Plasmodium falciparum is the infective agent responsible for malaria tropica. The glycogen synthase kinase-3 of the parasite (PfGSK-3) was suggested as a potential biological target for novel antimalarial drugs. Starting from hit structures identified in a high-throughput screening campaign, 3,6-diamino-4-(2-halophenyl)-2-benzoylthieno[2,3-b]pyridine-5-carbonitriles were discovered as a new class of PfGSK-3 inhibitors. Being less active on GSK-3 homologues of other species, the title compounds showed selectivity in favor of PfGSK-3. Taking into account the X-ray structure of a related molecule in complex with human GSK-3 (HsGSK-3), a model was computed for the comparison of inhibitor complexes with the plasmodial and human enzymes. It was found that subtle differences in the ATP-binding pockets are responsible for the observed PfGSK-3 vs HsGSK-3 selectivity. Representatives of the title compound class exhibited micromolar IC₅₀ values against P. falciparum erythrocyte stage parasites. These results suggest that inhibitors of PfGSK-3 could be developed as potential antimalarial drugs.
• New method for the synthesis of 6-amino-4-aryl-3,5-dicyano-3,4-dihydropyridine-2(1H)-thiones by recyclization of 4-aryl-2,6-diamino-4H-thiopyranes
  作者：V. D. Dyachenko、S. G. Krivokolysko、Yu. A. Sharanin、V. P. Litvinov

  DOI：10.1007/bf02253028

  日期：1997.7