4-{2-[(1E)-1-(naphthalen-1-ylmethylidene)-1H-inden-3-yl]ethyl}morpholine | 220080-15-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-{2-[(1E)-1-(naphthalen-1-ylmethylidene)-1H-inden-3-yl]ethyl}morpholine
• 英文别名: 4-(2-{3-[1-Naphthalen-1-yl-meth-(E)-ylidene]-3H-inden-1-yl}-ethyl)-morpholine；4-[2-[(3E)-3-(naphthalen-1-ylmethylidene)inden-1-yl]ethyl]morpholine
• CAS: 220080-15-9
• 化学式: C₂₆H₂₅NO
• 分子量: 367.491
• InChiKey: RTRAPBQOJODDGH-PTGBLXJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-{2-[(1E)-1-(naphthalen-1-ylmethylidene)-1H-inden-3-yl]ethyl}morpholine 以 乙醇 为溶剂， 反应 7.0h， 以8 mg的产率得到4-(2-{3-[1-Naphthalen-1-yl-meth-(Z)-ylidene]-3H-inden-1-yl}-ethyl)-morpholine
  参考文献：
  名称：

  大麻素CB1和CB2受体上氨基烷基吲哚的生物活性构象：从（E）-和（Z）-萘并茚基获得的见解。

  摘要：

  氨基烷基吲哚（AAI）是大麻素CB1和CB2受体的激动剂。为了确定AAI的s-反式或s-顺式形式是它们的受体合适的构象，研究了两对刚性的AAI类似物。这些刚性类似物是缺少AAI的羰基氧的亚萘基取代的氨基烷基茚。考虑了两对（E）-和（Z）-亚萘基（C-2 H和C-2 Me）。在每对中，E几何异构体旨在模仿AAI的s-反式，而Z几何异构体旨在模仿s-顺式。使用半经验方法AM1对两种AAI（pravadoline（2）和WIN-55、212-2（1））以及每种茚进行了完整的构象分析。鉴定出1和2的S-反式和s-顺式构象。AM1单点能量计算表明，当1和每个茚在相应的吲哚/茚环上重叠时，（E）-和（Z）-茚能够将萘环与相应的s-trans或s-cis重叠C-1 H（E / Z）茚的能量消耗为1.13 / 0.69 kcal / mol，C-2 Me（E / Z）茚的能量消耗为0.82 / 0.74 kcal

  DOI：

  10.1021/jm9801197
• 作为产物：
  描述：

  4-(2-氯乙基)吗啉 在 甲醇 、 正丁基锂 、 sodium methylate 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 23.92h， 生成 4-{2-[(1E)-1-(naphthalen-1-ylmethylidene)-1H-inden-3-yl]ethyl}morpholine
  参考文献：
  名称：

  Peripherally Selective Cannabinoid 1 Receptor (CB1R) Agonists for the Treatment of Neuropathic Pain

  摘要：

  Alleviation of neuropathic pain by cannabinoids is limited by their central nervous system (CNS) side effects. Indole and indene compounds were engineered for high hCB1R affinity, peripheral selectivity, metabolic stability, and in vivo efficacy. An epithelial cell line assay identified candidates with blood brain barrier penetration for testing in a rat neuropathy induced by unilateral sciatic nerve entrapment (SNE). The SNE-induced mechanical allodynia was reversibly suppressed, partially or completely, after intraperitoneal or oral administration of several indenes. At doses-that relieve neuropathy symptoms, the indenes completely lacked, while the brain-permeant CB1R agonist HU-210 (1) exhibited strong CNS side effects, in catalepsy, hypothermia, and motor incoordination assays. Pharmacokinetic findings of similar to 0.001 cerebrospinal fluid:plasma ratio further supported limited CNS penetration. Pretreatment with selective CB1R or CB2R blockers suggested mainly CB1R contribution to an indene's antiallodynic effects. Therefore, this class of CB1R agonists holds promise as a viable treatment for neuropathic pain.

  DOI：

  10.1021/acs.jmedchem.6b00516

文献信息

• [EN] PERIPHERALLY-ACTING CANNABINOID RECEPTOR AGONISTS FOR CHRONIC PAIN<br/>[FR] AGONISTES DE RÉCEPTEURS CANNABINOÏDES À ACTION PÉRIPHÉRIQUE CONTRE LA DOULEUR CHRONIQUE
  申请人：UNIV CALIFORNIA

  公开号：WO2014015298A1

  公开（公告）日：2014-01-23

  Peripherally acting cannabinoid agonist compounds, pharmaceutical compositions, and methods of using them are presented.

  外周作用的大麻素激动剂化合物、药物组合物以及使用它们的方法被提出。
• Antipruritics
  申请人：Yasui Kiyoshi

  公开号：US20080312292A1

  公开（公告）日：2008-12-18

  It is intended to provide antipruritics (drugs to control itching, antiitch agents and drugs to stop itching). It is found out that a compound having an agonistic activity to the cannabinoid receptor shows an antipruritics effect.

  这句话的意思是：它旨在提供止痒药（控制瘙痒的药物、抗瘙痒剂和止痒药物）。发现一种具有类脂激素受体激动活性的化合物具有止痒效果。
• PERIPHERALLY-ACTING CANNABINOID RECEPTOR AGONISTS FOR CHRONIC PAIN
  申请人：The Regents of the University of California

  公开号：US20150239859A1

  公开（公告）日：2015-08-27

  Peripherally acting cannabinoid agonist compounds, pharmaceutical compositions, and methods of using them are presented.

  本文介绍了外周作用的大麻素激动剂化合物、制药组合物以及使用它们的方法。
• US9656981B2
  申请人：——

  公开号：US9656981B2

  公开（公告）日：2017-05-23
• Peripherally Selective Cannabinoid 1 Receptor (CB1R) Agonists for the Treatment of Neuropathic Pain
  作者：Herbert H. Seltzman、Craig Shiner、Erin E. Hirt、Anne F. Gilliam、Brian F. Thomas、Rangan Maitra、Rod Snyder、Sherry L. Black、Purvi R. Patel、Yatendra Mulpuri、Igor Spigelman

  DOI：10.1021/acs.jmedchem.6b00516

  日期：2016.8.25

  Alleviation of neuropathic pain by cannabinoids is limited by their central nervous system (CNS) side effects. Indole and indene compounds were engineered for high hCB1R affinity, peripheral selectivity, metabolic stability, and in vivo efficacy. An epithelial cell line assay identified candidates with blood brain barrier penetration for testing in a rat neuropathy induced by unilateral sciatic nerve entrapment (SNE). The SNE-induced mechanical allodynia was reversibly suppressed, partially or completely, after intraperitoneal or oral administration of several indenes. At doses-that relieve neuropathy symptoms, the indenes completely lacked, while the brain-permeant CB1R agonist HU-210 (1) exhibited strong CNS side effects, in catalepsy, hypothermia, and motor incoordination assays. Pharmacokinetic findings of similar to 0.001 cerebrospinal fluid:plasma ratio further supported limited CNS penetration. Pretreatment with selective CB1R or CB2R blockers suggested mainly CB1R contribution to an indene's antiallodynic effects. Therefore, this class of CB1R agonists holds promise as a viable treatment for neuropathic pain.