1-(3-cyclohexylpropyl)-3(R^*),4(R^*)-dimethyl-4-(3-hydroxyphenyl)piperidine

• 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: 1-(3-cyclohexylpropyl)-3(R^*),4(R^*)-dimethyl-4-(3-hydroxyphenyl)piperidine
• 英文别名: 3-[1-(3-Cyclohexyl-propyl)-3,4-dimethyl-piperidin-4-yl]-phenol；3-[(3R,4R)-1-(3-cyclohexylpropyl)-3,4-dimethylpiperidin-4-yl]phenol
• 化学式: C₂₂H₃₅NO
• 分子量: 329.526
• InChiKey: DRIFNPBKGHUWAN-PGRDOPGGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  3-环己基丙酰氯 在 lithium aluminium tetrahydride 、 1,8-双二甲氨基萘 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 1-(3-cyclohexylpropyl)-3(R^*),4(R^*)-dimethyl-4-(3-hydroxyphenyl)piperidine
  参考文献：
  名称：

  3,4-Dimethyl-4-(3-hydroxyphenyl)piperidines: opioid antagonists with potent anorectant activity

  摘要：

  A series of (3R*,4R*)-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine opioid antagonists with varying substituents on the nitrogen were evaluated for their effect on food consumption in obese Zucker rats. Opioid affinity (mu, kappa, and delta for selected compounds) and opioid antagonist activity (mu and kappa) were characterized and compared to effects on food consumption. No compounds with high selectivity for either mu or kappa receptors were discovered. However, compounds in the series had exceptional potency as opioid antagonists and in reducing food consumption in the obese Zucker rat. In contrast, a few compounds with high potency as opioid antagonists had much weaker potency for inhibiting food consumption. (3R,4R)-3,4-Dimethyl-1-[(3S)-3-hydroxy-3-cyclohexyl-propyl]-4-(3-hydroxyphenyl)piperidine(11,LY255582)emerged as having the best activity profile, both in reducing food consumption and as an opioid antagonist. Compound 11 is a highly potent mu, kappa-, and delta-opioid antagonist with possible clinical utility as an appetite suppressant for weight loss.

  DOI：

  10.1021/jm00072a002

文献信息

• KAPPA OPIOID RECEPTOR LIGANDS
  申请人：Carroll Frank Ivy

  公开号：US20090264462A1

  公开（公告）日：2009-10-22

  Kappa opioid receptor antagonists are provided that yield significant improvements in functional binding assays to kappa opioid receptors, and the use of these antagonists in treatment of disease states that are ameliorated by binding of the kappa opioid receptor such as heroin or cocaine addictions.

  κ阿片受体拮抗剂提供了在κ阿片受体的功能结合测定中产生显著改善的结果，并且这些拮抗剂在治疗通过结合κ阿片受体得到缓解的疾病状态中的使用，例如海洛因或可卡因成瘾。
• OPIOID RECEPTOR ANTAGONISTS
  申请人：ELI LILLY AND COMPANY

  公开号：EP1727788B1

  公开（公告）日：2010-07-28
• US8048895B2
  申请人：——

  公开号：US8048895B2

  公开（公告）日：2011-11-01
• 3,4-Dimethyl-4-(3-hydroxyphenyl)piperidines: opioid antagonists with potent anorectant activity
  作者：Charles H. Mitch、J. David Leander、Laurane G. Mendelsohn、Walter N. Shaw、David T. Wong、Buddy E. Cantrell、Bryan G. Johnson、John K. Reel、John D. Snoddy

  DOI：10.1021/jm00072a002

  日期：1993.10

  A series of (3R*,4R*)-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine opioid antagonists with varying substituents on the nitrogen were evaluated for their effect on food consumption in obese Zucker rats. Opioid affinity (mu, kappa, and delta for selected compounds) and opioid antagonist activity (mu and kappa) were characterized and compared to effects on food consumption. No compounds with high selectivity for either mu or kappa receptors were discovered. However, compounds in the series had exceptional potency as opioid antagonists and in reducing food consumption in the obese Zucker rat. In contrast, a few compounds with high potency as opioid antagonists had much weaker potency for inhibiting food consumption. (3R,4R)-3,4-Dimethyl-1-[(3S)-3-hydroxy-3-cyclohexyl-propyl]-4-(3-hydroxyphenyl)piperidine(11,LY255582)emerged as having the best activity profile, both in reducing food consumption and as an opioid antagonist. Compound 11 is a highly potent mu, kappa-, and delta-opioid antagonist with possible clinical utility as an appetite suppressant for weight loss.