N-(3-fluoro-4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-benzofuran-2-carboxamide | 1301178-82-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N-(3-fluoro-4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-benzofuran-2-carboxamide
• 英文别名: N-[3-fluoro-4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]-1-benzofuran-2-carboxamide
• CAS: 1301178-82-4
• 化学式: C₂₄H₂₈FN₃O₃
• 分子量: 425.503
• InChiKey: VGOPWFPTLSPLJJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  58
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(3-fluoro-4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-benzofuran-2-carboxamide 、 草酸 以 丙酮 为溶剂， 生成 N-(3-fluoro-4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-benzofuran-2-carboxamide oxalate
  参考文献：
  名称：

  N-(3-Fluoro-4-(4-(2-methoxy or 2,3-dichlorophenyl)piperazine-1-yl)butyl)arylcarboxamides as Selective Dopamine D3 Receptor Ligands: Critical Role of the Carboxamide Linker for D3 Receptor Selectivity

  摘要：

  N-(3-Fluoro-4-(4-(2,3-dichloro- or 2-methoxyphenyl)piperazine-1-yl)butyl)arylcarboxamides were prepared and evaluated for binding and function at dopamine D3 receptors (D3Rs) and dopamine D2 receptors (D2Rs). In this series, we discovered some of the most D3R selective compounds reported to date (e.g., 8d and 8j, > 1000-fold D3R-selective over D2R). In addition, chimeric receptor studies further identified the second extracellular (E2) loop as an important contributor to D3R binding selectivity. Further, compounds lacking the carbonyl group in the amide linker were synthesized, and while these amine-linked analogues bound with similar affinities to the amides at D2R, this modification dramatically reduced binding affinities at D3R by > 100-fold (e.g., D3R K-i for 15b = 393 vs for 8j = 2.6 nM), resulting in compounds with significantly reduced D3R selectivity. This study supports a pivotal role for the D3R E2 loop and the carbonyl group in the 4-phenylpiperazine class of compounds and further reveals a point of separation between structure-activity relationships at D3R and D2R.

  DOI：

  10.1021/jm200288r
• 作为产物：
  描述：

  苯并呋喃-2-羧酸 在 氯化亚砜 、 sodium hydroxide 作用下， 以 氯仿 、 水 为溶剂， 反应 6.0h， 生成 N-(3-fluoro-4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-benzofuran-2-carboxamide
  参考文献：
  名称：

  N-(3-Fluoro-4-(4-(2-methoxy or 2,3-dichlorophenyl)piperazine-1-yl)butyl)arylcarboxamides as Selective Dopamine D3 Receptor Ligands: Critical Role of the Carboxamide Linker for D3 Receptor Selectivity

  摘要：

  N-(3-Fluoro-4-(4-(2,3-dichloro- or 2-methoxyphenyl)piperazine-1-yl)butyl)arylcarboxamides were prepared and evaluated for binding and function at dopamine D3 receptors (D3Rs) and dopamine D2 receptors (D2Rs). In this series, we discovered some of the most D3R selective compounds reported to date (e.g., 8d and 8j, > 1000-fold D3R-selective over D2R). In addition, chimeric receptor studies further identified the second extracellular (E2) loop as an important contributor to D3R binding selectivity. Further, compounds lacking the carbonyl group in the amide linker were synthesized, and while these amine-linked analogues bound with similar affinities to the amides at D2R, this modification dramatically reduced binding affinities at D3R by > 100-fold (e.g., D3R K-i for 15b = 393 vs for 8j = 2.6 nM), resulting in compounds with significantly reduced D3R selectivity. This study supports a pivotal role for the D3R E2 loop and the carbonyl group in the 4-phenylpiperazine class of compounds and further reveals a point of separation between structure-activity relationships at D3R and D2R.

  DOI：

  10.1021/jm200288r

文献信息

• <i>N</i>-(3-Fluoro-4-(4-(2-methoxy or 2,3-dichlorophenyl)piperazine-1-yl)butyl)arylcarboxamides as Selective Dopamine D3 Receptor Ligands: Critical Role of the Carboxamide Linker for D3 Receptor Selectivity
  作者：Ashwini K. Banala、Benjamin A. Levy、Sameer S. Khatri、Cheryse A. Furman、Rebecca A. Roof、Yogesh Mishra、Suzy A. Griffin、David R. Sibley、Robert R. Luedtke、Amy Hauck Newman

  DOI：10.1021/jm200288r

  日期：2011.5.26

  N-(3-Fluoro-4-(4-(2,3-dichloro- or 2-methoxyphenyl)piperazine-1-yl)butyl)arylcarboxamides were prepared and evaluated for binding and function at dopamine D3 receptors (D3Rs) and dopamine D2 receptors (D2Rs). In this series, we discovered some of the most D3R selective compounds reported to date (e.g., 8d and 8j, > 1000-fold D3R-selective over D2R). In addition, chimeric receptor studies further identified the second extracellular (E2) loop as an important contributor to D3R binding selectivity. Further, compounds lacking the carbonyl group in the amide linker were synthesized, and while these amine-linked analogues bound with similar affinities to the amides at D2R, this modification dramatically reduced binding affinities at D3R by > 100-fold (e.g., D3R K-i for 15b = 393 vs for 8j = 2.6 nM), resulting in compounds with significantly reduced D3R selectivity. This study supports a pivotal role for the D3R E2 loop and the carbonyl group in the 4-phenylpiperazine class of compounds and further reveals a point of separation between structure-activity relationships at D3R and D2R.