4-(2-hydroxy-5-methylphenoxy)-N-[(1S)-1-{[(3S)-4-(3-hydroxyphenyl)-3-methylpiperazin-1-yl]methyl}-2-methylpropyl]-3-methoxybenzamide | 1436378-73-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(2-hydroxy-5-methylphenoxy)-N-[(1S)-1-{[(3S)-4-(3-hydroxyphenyl)-3-methylpiperazin-1-yl]methyl}-2-methylpropyl]-3-methoxybenzamide
• 英文别名: 4-(2-hydroxy-5-methylphenoxy)-N-[(2S)-1-[(3S)-4-(3-hydroxyphenyl)-3-methylpiperazin-1-yl]-3-methylbutan-2-yl]-3-methoxybenzamide
• CAS: 1436378-73-2
• 化学式: C₃₁H₃₉N₃O₅
• 分子量: 533.668
• InChiKey: PGYWNPFFRWTCDQ-BKMJKUGQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  39
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  94.5
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-(2-hydroxy-5-methylphenoxy)-N-[(1S)-1-{[(3S)-4-(3-hydroxyphenyl)-3-methylpiperazin-1-yl]methyl}-2-methylpropyl]-3-methoxybenzamide 在 盐酸 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 以53%的产率得到4-(2-hydroxy-5-methylphenoxy)-N-[(1S)-1-{[(3S)-4-(3-hydroxyphenyl)-3-methylpiperazin-1-yl]methyl}-2-methylpropyl]-3-methoxybenzamide dihydrochloride
  参考文献：
  名称：

  Discovery of N-{4-[(3-Hydroxyphenyl)-3-methylpiperazin-1-yl]methyl-2-methylpropyl}-4-phenoxybenzamide Analogues as Selective Kappa Opioid Receptor Antagonists

  摘要：

  There is continuing interest in the discovery and development of new kappa opioid receptor antagonists. We recently reported that N-substituted 3-methyl-4-(3-hydroxyphenyl)piperazines were a new class of opioid receptor antagonists. In this study, we report the syntheses of two piperazine JDTic-like analogues. Evaluation of the two compounds in an in vitro [S-35]GTP gamma S binding assay showed that neither compound showed the high potency and kappa opioid receptor selectivity of JDTic. A library of compounds using the core scaffold 21 was synthesized and tested for their ability to inhibit [S-35]GTP gamma S binding stimulated by the selective kappa opioid agonist U69,593. These studies led to N-[(1S)-1-{[(3S)-4-(3-hydroxyphenyl)-3-methylpiperazin-1-yl]methyll-2-methylpropyl]-4-phenoxybenzamide (11a), a compound that showed good kappa opioid receptor antagonist properties. An SAR study based on 11a provided 28 novel analogues. Evaluation of these 28 compounds in the [S-35]GTP gamma S binding assay showed that several of the analogues were potent and selective kappa opioid receptor antagonists.

  DOI：

  10.1021/jm400275h
• 作为产物：
  描述：

  3-甲氧基-4-氟苯甲醛 在 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 12.33h， 生成 4-(2-hydroxy-5-methylphenoxy)-N-[(1S)-1-{[(3S)-4-(3-hydroxyphenyl)-3-methylpiperazin-1-yl]methyl}-2-methylpropyl]-3-methoxybenzamide
  参考文献：
  名称：

  Discovery of N-{4-[(3-Hydroxyphenyl)-3-methylpiperazin-1-yl]methyl-2-methylpropyl}-4-phenoxybenzamide Analogues as Selective Kappa Opioid Receptor Antagonists

  摘要：

  There is continuing interest in the discovery and development of new kappa opioid receptor antagonists. We recently reported that N-substituted 3-methyl-4-(3-hydroxyphenyl)piperazines were a new class of opioid receptor antagonists. In this study, we report the syntheses of two piperazine JDTic-like analogues. Evaluation of the two compounds in an in vitro [S-35]GTP gamma S binding assay showed that neither compound showed the high potency and kappa opioid receptor selectivity of JDTic. A library of compounds using the core scaffold 21 was synthesized and tested for their ability to inhibit [S-35]GTP gamma S binding stimulated by the selective kappa opioid agonist U69,593. These studies led to N-[(1S)-1-{[(3S)-4-(3-hydroxyphenyl)-3-methylpiperazin-1-yl]methyll-2-methylpropyl]-4-phenoxybenzamide (11a), a compound that showed good kappa opioid receptor antagonist properties. An SAR study based on 11a provided 28 novel analogues. Evaluation of these 28 compounds in the [S-35]GTP gamma S binding assay showed that several of the analogues were potent and selective kappa opioid receptor antagonists.

  DOI：

  10.1021/jm400275h

文献信息

• Discovery of <i>N</i>-{4-[(3-Hydroxyphenyl)-3-methylpiperazin-1-yl]methyl-2-methylpropyl}-4-phenoxybenzamide Analogues as Selective Kappa Opioid Receptor Antagonists
  作者：Chad M. Kormos、Chunyang Jin、Juan Pablo Cueva、Scott P. Runyon、James B. Thomas、Lawrence E. Brieaddy、S. Wayne Mascarella、Hernán A. Navarro、Brian P. Gilmour、F. Ivy Carroll

  DOI：10.1021/jm400275h

  日期：2013.6.13

  There is continuing interest in the discovery and development of new kappa opioid receptor antagonists. We recently reported that N-substituted 3-methyl-4-(3-hydroxyphenyl)piperazines were a new class of opioid receptor antagonists. In this study, we report the syntheses of two piperazine JDTic-like analogues. Evaluation of the two compounds in an in vitro [S-35]GTP gamma S binding assay showed that neither compound showed the high potency and kappa opioid receptor selectivity of JDTic. A library of compounds using the core scaffold 21 was synthesized and tested for their ability to inhibit [S-35]GTP gamma S binding stimulated by the selective kappa opioid agonist U69,593. These studies led to N-[(1S)-1-[(3S)-4-(3-hydroxyphenyl)-3-methylpiperazin-1-yl]methyll-2-methylpropyl]-4-phenoxybenzamide (11a), a compound that showed good kappa opioid receptor antagonist properties. An SAR study based on 11a provided 28 novel analogues. Evaluation of these 28 compounds in the [S-35]GTP gamma S binding assay showed that several of the analogues were potent and selective kappa opioid receptor antagonists.