4,6-diethyl-2-mercaptopyrimidine | 143946-43-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4,6-diethyl-2-mercaptopyrimidine
• 英文别名: 4,6-Diethyl-pyrimidine-2-thiol；4,6-diethyl-1H-pyrimidine-2-thione
• CAS: 143946-43-4
• 化学式: C₈H₁₂N₂S
• 分子量: 168.263
• InChiKey: ADBFEHDZTNSHFK-UHFFFAOYSA-N

物化性质

• 沸点：
  249.8±23.0 °C(Predicted)
• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  56.5
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4,6-diethyl-2-mercaptopyrimidine 在 过氧乙酸 、 lithium hydroxide 、 sodium hydroxide 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 rac-(SR)-(4,6-diethylpyrimidin-2-yloxy)-{(5SR)-1-methyl-2-oxo-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-5-yl}acetic acid
  参考文献：
  名称：

  Novel Benzo[1,4]diazepin-2-one Derivatives as Endothelin Receptor Antagonists

  摘要：

  Since its discovery in 1988 by Yanagisawa et al., endothelin (ET), a potent vasoconstrictor, has been widely implicated in the pathophysiology of cardiovascular, cerebrovascular, and renal diseases. Many research groups have embarked on the discovery and development of ET receptor antagonists for the treatment of such diseases. While several compounds, e.g., ambrisentan 2, are in late clinical trials for various indications, one compound (bosentan, Tracleer) is being marketed to treat pulmonary arterial hypertension. Inspired by the structure of ambrisentan 2, we designed a novel class of ET receptor antagonists based on a 1,3,4,5-tetrahydro-1H-benzo[e] [1,4]diazepin-2-one scaffold. Here, we report on the preparation as well as the in vitro and in vivo structure-activity relationships of these derivatives. Potent dual ETA/ETB receptor antagonists with affinities in the low nanomolar range have been identified. In addition, several compounds efficiently reduced arterial blood pressure after oral administration to Dahl salt sensitive rats. In this animal model, the efficacy of the benzo [e] [1,4] diazepin-2-one derivative rac-39au was superior to that of racemic ambrisentan, rac-2.

  DOI：

  10.1021/jm031115r
• 作为产物：
  描述：

  3,5-庚烷二酮 在 盐酸 、 硫脲 作用下， 以 乙醇 、 水 为溶剂， 以53%的产率得到4,6-diethyl-2-mercaptopyrimidine
  参考文献：
  名称：

  Pyrimidinyloxy(thio)quinoline derivative, and agri-horticultural

  摘要：

  公开了由公式(I)代表的嘧啶氧(硫)喹啉衍生物，这些衍生物对植物病害具有出色的控制效果，并且对作物植物安全，还公开了这些衍生物的制备过程，以及以这些衍生物作为活性成分的农业园艺杀菌剂。在公式(I)中，X是氧原子或硫原子，Y是氢原子或卤素原子，Z是氢原子或甲基，R.sup.1和R.sup.2是甲氧基或甲基，n是1或2的整数。

  公开号：

  US05202329A1

文献信息

• Aminothiazoles as Potent and Selective Sirt2 Inhibitors: A Structure–Activity Relationship Study
  作者：Matthias Schiedel、Tobias Rumpf、Berin Karaman、Attila Lehotzky、Judit Oláh、Stefan Gerhardt、Judit Ovádi、Wolfgang Sippl、Oliver Einsle、Manfred Jung

  DOI：10.1021/acs.jmedchem.5b01517

  日期：2016.2.25

  Here, we present a well-defined structure–activity relationship study, which rationalizes the unique features of the SirReals and probes the limits of modifications on this scaffold regarding inhibitor potency. Moreover, we present a crystal structure of hSirt2 in complex with an optimized SirReal derivative that exhibits an improved in vitro activity. Lastly, we show cellular hyperacetylation of the

  Sirtuins是NAD +-依赖性蛋白脱酰基酶，其从组蛋白和其他底物蛋白中的赖氨酸的ε-氨基上裂解掉乙酰基以及其他酰基。人类Sirt2（hSirt2）活性的失调与癌症，炎症和神经退行性病变的发病机制有关，这使得对hSirt2活性的调节成为药物干预的有前途的策略。sirtuin重排配体（SirReals）最近已被我们发现为高效且同型选择性的hSirt2抑制剂。在这里，我们提出了一个定义明确的结构-活性关系研究，该研究合理化了SirReals的独特功能，并探讨了该支架在抑制剂效能方面的修饰极限。而且，我们提出了具有优化的SirReal衍生物的hSirt2晶体结构，该衍生物具有改善的体外活性。最后，我们显示了由我们改良的前导结构导致的hSirt2靶向微管蛋白的细胞过度乙酰化。
• Novel benzo-fused heterocycles as endothelin antagonisits
  申请人：Bolli Martin

  公开号：US20050124605A1

  公开（公告）日：2005-06-09

  The invention relates to novel benzo-fused heterocycles and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as endothelin receptor antagonists.

  本发明涉及新型苯并杂环化合物及其用作制备药物组成物的活性成分。本发明还涉及相关方面，包括制备化合物的过程，含有其中一种或多种化合物的药物组成物，特别是它们作为内皮素受体拮抗剂的用途。
• Pyrimidinyloxy(thio)quinoline derivatives, preparation process of the derivative, and agri-horticultural fungicide comprising the derivative as active ingredient
  申请人：MITSUI CHEMICALS, INC.

  公开号：EP0497371B1

  公开（公告）日：1998-06-24
• US3963495A
  申请人：——

  公开号：US3963495A

  公开（公告）日：1976-06-15
• US5202329A
  申请人：——

  公开号：US5202329A

  公开（公告）日：1993-04-13