5-hydroxy-2-((4-methylphenylthio)methyl)-4H-pyran-4-one | 204503-12-8

• 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-((4-methylphenylthio)methyl)-4H-pyran-4-one
• 英文别名: 5-hydroxy-2-((p-tolylthio)methyl)-4H-pyran-4-one；5-hydroxy-2-[(4-methylphenyl)sulfanylmethyl]pyran-4-one
• CAS: 204503-12-8
• 化学式: C₁₃H₁₂O₃S
• 分子量: 248.302
• InChiKey: DIGIPUKDOUXMTL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  71.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-hydroxy-2-((4-methylphenylthio)methyl)-4H-pyran-4-one 、 3-硝基-4-氯苯甲酰氯 在 caesium carbonate 作用下， 以 乙腈 为溶剂， 生成 [6-[(4-Methylphenyl)sulfanylmethyl]-4-oxopyran-3-yl] 4-chloro-3-nitrobenzoate
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2012.08.105
• 作为产物：
  描述：

  曲酸 在 氯化亚砜 、 sodium methylate 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 6.0h， 生成 5-hydroxy-2-((4-methylphenylthio)methyl)-4H-pyran-4-one
  参考文献：
  名称：

  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

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2012.08.105

文献信息

• Inhibitory Activities of Kojyl Thioether Derivatives against Nitric Oxide Production Induced by Lipopolysaccharide
  作者：Ho-Sik Rho、Dae-Sung Yoo、Soo-Mi Ahn、Myung-Kyoo Kim、Dong-Ha Cho、Jae-Youl Cho

  DOI：10.5012/bkcs.2010.31.11.3463

  日期：2010.11.20
• 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.