2-fluoro-4-(2-(4-(2-(1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)piperazin-1-yl)ethyl)benzonitrile | 1372151-41-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异香豆素
• 英文名称: 2-fluoro-4-(2-(4-(2-(1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)piperazin-1-yl)ethyl)benzonitrile
• 英文别名: 2-fluoro-4-[2-[4-[2-(1-oxo-3H-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]benzonitrile
• CAS: 1372151-41-1
• 化学式: C₂₃H₂₄FN₃O₂
• 分子量: 393.461
• InChiKey: XPHJICKYBJRKLW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  56.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-氟-4-羟基苯乙酸 在 4-二甲氨基吡啶 、 锂硼氢 、 四(三苯基膦)钯 、 氯化亚砜 、 戴斯-马丁氧化剂 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 69.5h， 生成 2-fluoro-4-(2-(4-(2-(1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)piperazin-1-yl)ethyl)benzonitrile
  参考文献：
  名称：

  Discovery of Selective Small Molecule ROMK Inhibitors as Potential New Mechanism Diuretics

  摘要：

  The renal outer medullary potassium channel (ROMK or K(ir)1.1) is a putative drug target for a novel class of diuretics that could be used for the treatment of hypertension and edematous states such as heart failure. An internal high-throughput screening campaign identified 1,4-bis(4-nitrophenethyl)piperazine (5) as a potent ROMK inhibitor. It is worth noting that this compound was identified as a minor impurity in a screening hit that was responsible for all of the initially observed ROMK activity. Structure-activity studies resulted in analogues with improved rat pharmacokinetic properties and selectivity over the hERG channel, providing tool compounds that can be used for in vivo pharmacological assessment. The featured ROMK inhibitors were also selective against other members of the inward rectifier family of potassium channels.

  DOI：

  10.1021/ml3000066

文献信息

• INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP2632465B1

  公开（公告）日：2015-12-30
• US9073882B2
  申请人：——

  公开号：US9073882B2

  公开（公告）日：2015-07-07
• [EN] INHIBITORS OF THE RENAL OUTER MEDULLARY POTASSIUM CHANNEL<br/>[FR] INHIBITEURS DU CANAL POTASSIQUE DE LA MÉDULLAIRE EXTERNE RÉNALE
  申请人：MERCK SHARP & DOHME

  公开号：WO2012058116A1

  公开（公告）日：2012-05-03

  This invention relates to compounds having structural Formula I: and pharmaceutically acceptable salts thereof which are inhibitors of the Renal Outer Medullary Potassium (ROMK) channel (Kirl.1). The compounds of Formula I are useful as diuretics and natriuretics and therefore are useful for the therapy and prophylaxis of disorders resulting from excessive salt and water retention, including cardiovascular diseases such as hypertension and chronic and acute heart failure.
• Discovery of Selective Small Molecule ROMK Inhibitors as Potential New Mechanism Diuretics
  作者：Haifeng Tang、Shawn P. Walsh、Yan Yan、Reynalda K. de Jesus、Aurash Shahripour、Nardos Teumelsan、Yuping Zhu、Sookhee Ha、Karen A. Owens、Brande S. Thomas-Fowlkes、John P. Felix、Jessica Liu、Martin Kohler、Birgit T. Priest、Timothy Bailey、Richard Brochu、Magdalena Alonso-Galicia、Gregory J. Kaczorowski、Sophie Roy、Lihu Yang、Sander G. Mills、Maria L. Garcia、Alexander Pasternak

  DOI：10.1021/ml3000066

  日期：2012.5.10

  The renal outer medullary potassium channel (ROMK or K(ir)1.1) is a putative drug target for a novel class of diuretics that could be used for the treatment of hypertension and edematous states such as heart failure. An internal high-throughput screening campaign identified 1,4-bis(4-nitrophenethyl)piperazine (5) as a potent ROMK inhibitor. It is worth noting that this compound was identified as a minor impurity in a screening hit that was responsible for all of the initially observed ROMK activity. Structure-activity studies resulted in analogues with improved rat pharmacokinetic properties and selectivity over the hERG channel, providing tool compounds that can be used for in vivo pharmacological assessment. The featured ROMK inhibitors were also selective against other members of the inward rectifier family of potassium channels.