(+)-3-((αR)-α-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-benzyl-N-methylbenzamide

• 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: (+)-3-((αR)-α-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-benzyl-N-methylbenzamide
• 英文别名: 3-[(R)-((2S,5R)-4-Allyl-2,5-dimethyl-piperazin-1-yl)-(3-hydroxy-phenyl)-methyl]-N-benzyl-N-methyl-benzamide；N-benzyl-3-[(R)-[(2S,5R)-2,5-dimethyl-4-prop-2-enylpiperazin-1-yl]-(3-hydroxyphenyl)methyl]-N-methylbenzamide
• 化学式: C₃₁H₃₇N₃O₂
• 分子量: 483.654
• InChiKey: APSQTBDUIGGKRT-FSGGQHMVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  47
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (+)-3-((αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-bromobenzyl)phenol 在 咪唑 、 sodium hydroxide 、 草酰氯 、 四乙基氟化铵水合物 、 三乙胺 、 N,N-二甲基甲酰胺 、 sodium chloride 作用下， 以 N-甲基吡咯烷酮 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 127.5h， 生成 (+)-3-((αR)-α-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-benzyl-N-methylbenzamide
  参考文献：
  名称：

  3-(αR)-α-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)- N-alkyl-N-arylbenzamides:  Potent, Non-Peptidic Agonists of Both the μ and δ Opioid Receptors

  摘要：

  Opioid analgesics with both mu and delta opioid receptor activation represent a new approach to the treatment of severe pain with an improved safety profile. Compounds with this profile may exhibit strong analgesic properties due to mu agonism, with a reduced side effect profile resulting from delta agonism. Replacing the p-diethylamide of the known potent delta opioid receptor selective agonist BW373U86 with a m-diethylamide resulted in a compound with agonist activity at both the mu and delta opioid receptors. Modifying the amide to an N-methyl-N-phenylamide increased agonist potency at both receptors. A series of 3-(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-alkyl-N-arylbenzamides have been made to explore the structure-activity relationship (SAR) around the N-methyl-N-phenylamide. Several potent agonists of both the mu and delta opioid receptors have been identified, including (+)-3-((alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-l-piperazinyl)-3-hydroxybenzyl)-N-(4-fluorophenyl)-N-methylben-zamide (23), which has EC50 values of 0.67 and 1.1 nM at the mu (guinea pig ileum assay) and delta (mouse vas deferens assay) opioid receptors, respectively.

  DOI：

  10.1021/jm020395s

文献信息

• COMPOSITIONS AND METHODS FOR REDUCING RESPIRATORY DEPRESSION AND ATTENDANT SIDE EFFECTS OF MU OPIOID COMPOUNDS
  申请人：Chang Kwen-Jen

  公开号：US20080193383A1

  公开（公告）日：2008-08-14

  A method of reducing, treating or preventing drug-mediated respiratory depression, muscle rigidity, or nausea/vomiting in an animal, incident to the administration to said animal of a mixed delta/mu opioid agonist or a respiratory depression-mediating drug, comprising administering to the animal receiving said drug an effective amount of a delta receptor agonist compound. Preferred examples of such delta receptor agonist compound include diarylmethyl piperazine compounds and diarylmethyl piperidine compounds, and pharmaceutical compositions thereof, having utility in medical therapy for reducing respiratory depression associated with certain analgesics, such as mu opiates.

  一种减少、治疗或预防动物在接受混合的δ/μ阿片受体激动剂或呼吸抑制介导药物时发生的呼吸抑制、肌肉僵硬或恶心/呕吐的方法，包括向接受该药物的动物投予有效量的δ受体激动剂化合物。这种δ受体激动剂化合物的首选示例包括二芳基甲基哌嗪化合物和二芳基甲基哌啶化合物及其制药组合物，在医疗治疗中用于减少与某些镇痛剂（如μ阿片类药物）相关的呼吸抑制。
• US5552404A
  申请人：——

  公开号：US5552404A

  公开（公告）日：1996-09-03
• US5574159A
  申请人：——

  公开号：US5574159A

  公开（公告）日：1996-11-12
• US5681830A
  申请人：——

  公开号：US5681830A

  公开（公告）日：1997-10-28
• 3-(α<i>R</i>)-α-((2<i>S</i>,5<i>R</i>)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-<i> N</i>-alkyl-<i>N</i>-arylbenzamides:  Potent, Non-Peptidic Agonists of Both the μ and δ Opioid Receptors
  作者：Michael J. Bishop、Dulce M. Garrido、G. Evan Boswell、Mark A. Collins、Philip A. Harris、Robert W. McNutt、Scott J. O'Neill、Ke Wei、Kwen-Jen Chang

  DOI：10.1021/jm020395s

  日期：2003.2.1

  Opioid analgesics with both mu and delta opioid receptor activation represent a new approach to the treatment of severe pain with an improved safety profile. Compounds with this profile may exhibit strong analgesic properties due to mu agonism, with a reduced side effect profile resulting from delta agonism. Replacing the p-diethylamide of the known potent delta opioid receptor selective agonist BW373U86 with a m-diethylamide resulted in a compound with agonist activity at both the mu and delta opioid receptors. Modifying the amide to an N-methyl-N-phenylamide increased agonist potency at both receptors. A series of 3-(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-alkyl-N-arylbenzamides have been made to explore the structure-activity relationship (SAR) around the N-methyl-N-phenylamide. Several potent agonists of both the mu and delta opioid receptors have been identified, including (+)-3-((alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-l-piperazinyl)-3-hydroxybenzyl)-N-(4-fluorophenyl)-N-methylben-zamide (23), which has EC50 values of 0.67 and 1.1 nM at the mu (guinea pig ileum assay) and delta (mouse vas deferens assay) opioid receptors, respectively.