5-hydroxy-2-((pyrimidin-2-ylthio)methyl)-4H-pyran-4-one | 941868-82-2

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 5-hydroxy-2-((pyrimidin-2-ylthio)methyl)-4H-pyran-4-one
• 英文别名: 5-hydroxy-2-(pyrimidin-2-ylsulfanylmethyl)pyran-4-one
• CAS: 941868-82-2
• 化学式: C₁₀H₈N₂O₃S
• mdl: MFCD09743102
• 分子量: 236.251
• InChiKey: RIGMECGKVLFSIH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  97.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-hydroxy-2-((pyrimidin-2-ylthio)methyl)-4H-pyran-4-one 、 4-硝基苯甲酰氯 在 caesium carbonate 作用下， 以 乙腈 为溶剂， 以202 mg的产率得到5-[(4-硝基苯甲酰基)氧基]-2-[(2-嘧啶硫基)甲基]-4H-吡喃-4-酮
  参考文献：
  名称：

  SMALL MOLECULE ANTAGONISTS OF THE APELIN RECEPTOR FOR THE TREATMENT OF DISEASE

  摘要：

  本公开涉及化合物和治疗通过apelin介导的疾病的方法。

  公开号：

  US20140005181A1
• 作为产物：
  描述：

  2-(bromomethyl)-5-((4-methoxybenzyl)oxy)-4H-pyran-4-one 在 sodium hydride 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 49.0h， 生成 5-hydroxy-2-((pyrimidin-2-ylthio)methyl)-4H-pyran-4-one
  参考文献：
  名称：

  Synthesis of kojic acid derivatives as secondary binding site probes of d-amino acid oxidase

  摘要：

  A series of kojic acid (5-hydroxy-2-hydroxymethyl-4H-pyran-4-one) derivatives were synthesized and tested for their ability to inhibit D-amino acid oxidase (DAAO). Various substituents were incorporated into kojic acid at its 2-hydroxymethyl group. These analogs serve as useful molecular probes to explore the secondary binding site, which can be exploited in designing more potent DAAO inhibitors. (c) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.04.062

文献信息

• Discovery of 4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4-nitrobenzoate (ML221) as a functional antagonist of the apelin (APJ) receptor
  作者：Patrick R. Maloney、Pasha Khan、Michael Hedrick、Palak Gosalia、Monika Milewski、Linda Li、Gregory P. Roth、Eduard Sergienko、Eigo Suyama、Eliot Sugarman、Kevin Nguyen、Alka Mehta、Stefan Vasile、Ying Su、Derek Stonich、Hung Nguyen、Fu-Yue Zeng、Arianna Mangravita Novo、Michael Vicchiarelli、Jena Diwan、Thomas D.Y. Chung、Layton H. Smith、Anthony B. Pinkerton

  DOI：10.1016/j.bmcl.2012.08.105

  日期：2012.11

  The recently discovered apelin/APJ system has emerged as a critical mediator of cardiovascular homeostasis and is associated with the pathogenesis of cardiovascular disease. A role for apelin/APJ in energy metabolism and gastrointestinal function has also recently emerged. We disclose the discovery and characterization of 4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4-nitrobenzoate (ML221), a potent APJ functional antagonist in cell-based assays that is >37-fold selective over the closely related angiotensin II type 1 (AT1) receptor. ML221 was derived from an HTS of the similar to 330,600 compound MLSMR collection. This antagonist showed no significant binding activity against 29 other GPCRs, except to the kappa-opioid and benzodiazepinone receptors (<50/<70%I at 10 mu M). The synthetic methodology, development of structure-activity relationship (SAR), and initial in vitro pharmacologic characterization are also presented. (C) 2012 Elsevier Ltd. All rights reserved.