4-(3-hydroxyphenyl)-3(R),4(R)-dimethyl-2'(SR)-(phenylmethyl)-1-piperidinepropanoic acid ethyl ester

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-(3-hydroxyphenyl)-3(R),4(R)-dimethyl-2'(SR)-(phenylmethyl)-1-piperidinepropanoic acid ethyl ester
• 英文别名: ethyl 2-benzyl-3-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidin-1-yl]propanoate
• 化学式: C₂₅H₃₃NO₃
• 分子量: 395.542
• InChiKey: MZDPMYOGAUMOKW-ZUSIFUOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(3-hydroxyphenyl)-3(R),4(R)-dimethyl-2'(SR)-(phenylmethyl)-1-piperidinepropanoic acid ethyl ester 在 盐酸 、 lithium hydroxide 、 1-羟基苯并三唑一水物 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 81.0h， 生成 爱维莫潘
  参考文献：
  名称：

  Discovery of a Potent, Peripherally Selective trans-3,4-Dimethyl-4-(3-hydroxyphenyl)piperidine Opioid Antagonist for the Treatment of Gastrointestinal Motility Disorders

  摘要：

  Structure-activity relationship studies were pursued within N-substituted-trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines in an effort to discover a peripherally selective opioid antagonist with high activity following systemic administration. Altering the size and the polarity of the N-substituent led to the discovery of 3 (LY246736). Compound 3 has high affinity for opioid receptors (K-i = 0.77, 40, and 4.4 nM for mu, kappa, and delta receptors, respectively). It is a potent mu receptor antagonist following parenteral and oral administration and distributes selectively (>200-fold selectivity) to peripheral receptors. Thus, 3 has properties suitable for the clinical investigation of mu opioid receptor involvement in GI motility disorders.

  DOI：

  10.1021/jm00041a003
• 作为产物：
  描述：

  乙基2-苄基丙烯酸酯 、 (3R,4R)-3,4-二甲基-4-(3-羟基苯基)哌啶 以 甲醇 为溶剂， 反应 240.0h， 以8.0 g的产率得到4-(3-hydroxyphenyl)-3(R),4(R)-dimethyl-2'(SR)-(phenylmethyl)-1-piperidinepropanoic acid ethyl ester
  参考文献：
  名称：

  Discovery of a Potent, Peripherally Selective trans-3,4-Dimethyl-4-(3-hydroxyphenyl)piperidine Opioid Antagonist for the Treatment of Gastrointestinal Motility Disorders

  摘要：

  Structure-activity relationship studies were pursued within N-substituted-trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines in an effort to discover a peripherally selective opioid antagonist with high activity following systemic administration. Altering the size and the polarity of the N-substituent led to the discovery of 3 (LY246736). Compound 3 has high affinity for opioid receptors (K-i = 0.77, 40, and 4.4 nM for mu, kappa, and delta receptors, respectively). It is a potent mu receptor antagonist following parenteral and oral administration and distributes selectively (>200-fold selectivity) to peripheral receptors. Thus, 3 has properties suitable for the clinical investigation of mu opioid receptor involvement in GI motility disorders.

  DOI：

  10.1021/jm00041a003

文献信息

• Discovery of a Potent, Peripherally Selective trans-3,4-Dimethyl-4-(3-hydroxyphenyl)piperidine Opioid Antagonist for the Treatment of Gastrointestinal Motility Disorders
  作者：Dennis M. Zimmerman、Jaswant S. Gidda、Buddy E. Cantrell、Darryle D. Schoepp、Bryan G. Johnson、J. David Leander

  DOI：10.1021/jm00041a003

  日期：1994.7

  Structure-activity relationship studies were pursued within N-substituted-trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines in an effort to discover a peripherally selective opioid antagonist with high activity following systemic administration. Altering the size and the polarity of the N-substituent led to the discovery of 3 (LY246736). Compound 3 has high affinity for opioid receptors (K-i = 0.77, 40, and 4.4 nM for mu, kappa, and delta receptors, respectively). It is a potent mu receptor antagonist following parenteral and oral administration and distributes selectively (>200-fold selectivity) to peripheral receptors. Thus, 3 has properties suitable for the clinical investigation of mu opioid receptor involvement in GI motility disorders.