3-((αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-cyclopropyl-N-phenylbenzamide

• 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-cyclopropyl-N-phenylbenzamide
• 英文别名: 3-((alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-cyclopropyl-N-phenylbenzamide；N-cyclopropyl-3-[(R)-[(2S,5R)-2,5-dimethyl-4-prop-2-enylpiperazin-1-yl]-(3-hydroxyphenyl)methyl]-N-phenylbenzamide
• 化学式: C₃₂H₃₇N₃O₂
• 分子量: 495.665
• InChiKey: QJIRJFCKPGNFTF-ULPIOCOXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.34
• 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：

  三苯基铋 在 copper diacetate 、 四乙基氟化铵水合物 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 19.0h， 生成 3-((αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-cyclopropyl-N-phenylbenzamide
  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

• Opioid compounds
  申请人：Delta Pharmaceuticals, Inc.

  公开号：US05681830A1

  公开（公告）日：1997-10-28

  Diarylmethyl piperazine compounds having utility as exogenous receptor combinant species for binding with receptors such as delta, mu, sigma, and/or kappa receptors are disclosed. Compounds of the invention may be employed as conjugates in agonist/antagonist pairs for transductional monitoring and assays of neurotransmitter function, and also variously exhibit therapeutic utility, including mediating analgesia, and possessing utility for the treatment of diarrhea, urinary incontinence, mental illness, drug and alcohol addiction/overdose, lung edema, depression, asthma, emphysema, cough, and apnea, respiratory depression, cognitive disorders, emesis and gastrointestinal disorders.

  本发明揭示了具有作为外源受体结合物种与诸如δ、μ、σ和/或κ受体结合的效用的二苯甲基哌嗪化合物。该发明的化合物可以作为激动剂/拮抗剂对用于神经递质功能的转导监测和测定中的共轭物，并且还具有各种治疗效用，包括介导镇痛作用，并具有治疗腹泻、尿失禁、精神疾病、药物和酒精成瘾/过量、肺水肿、抑郁症、哮喘、肺气肿、咳嗽和呼吸暂停、呼吸抑制、认知障碍、呕吐和胃肠道疾病的效用。
• Opioid compounds and methods for using same
  申请人：Delta Pharmaceuticals, Inc.

  公开号：US05552404A1

  公开（公告）日：1996-09-03

  Diarylmethyl piperazine compounds having utility as exogenous receptor combinant species for binding with receptors such as delta, mu, sigma, and/or kappa receptors are disclosed. Compounds of the invention may be employed as conjugates in agonist/antagonist pairs for transductional monitoring and assays of neurotransmitter function, and also variously exhibit therapeutic utility, including mediating analgesia, and possessing utility for the treatment of diarrhea, urinary incontinence, mental illness, drug and alcohol addiction/overdose, lung edema, depression, asthma, emphysema, cough, and apnea, respiratory depression, cognitive disorders, emesis and gastrointestinal disorders.

  本发明公开了具有作为外源受体组合物种类的功能的二芳基甲基哌嗪化合物，用于与δ、μ、σ和/或κ受体等受体结合。本发明的化合物可以作为激动剂/拮抗剂对共轭体在神经递质功能的转导监测和测定中使用，并且还可以表现出各种治疗效用，包括介导镇痛作用，并具有治疗腹泻、尿失禁、精神疾病、药物和酒精成瘾/过量、肺水肿、抑郁症、哮喘、肺气肿、咳嗽和呼吸暂停、呼吸抑制、认知障碍、呕吐和胃肠道疾病的效用。
• Opioid compounds and methods for making therefor
  申请人：Delta Pharmaceuticals, Inc.

  公开号：US05574159A1

  公开（公告）日：1996-11-12

  Diarylmethyl piperazine compounds having utility as exogenous receptor combinant species for binding with receptors such as delta, mu, sigma, and/or kappa receptors are disclosed. Compounds of the invention may be employed as conjugates in agonist/antagonist pairs for transductional monitoring and assays of neurotransmitter function, and also variously exhibit therapeutic utility, including mediating analgesia, and possessing utility for the treatment of diarrhea, urinary incontinence, mental illness, drug and alcohol addiction/overdose, lung edema, depression, asthma, emphysema, cough, and apnea, respiratory depression, cognitive disorders, emesis and gastrointestinal disorders.

  本发明揭示了具有外源性受体结合物种功能的二芳甲基哌嗪化合物，用于与δ、μ、σ和/或κ受体结合。本发明的化合物可作为激动剂/拮抗剂对中的共轭物，在神经递质功能的传导监测和检测中使用，并且也具有各种治疗效用，包括介导镇痛，并具有治疗腹泻、尿失禁、精神疾病、药物和酒精成瘾/过量、肺水肿、抑郁症、哮喘、肺气肿、咳嗽和呼吸暂停、呼吸抑制、认知障碍、呕吐和胃肠疾病的功效。
• PIPERAZINE COMPOUNDS USED IN THERAPY
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0711289A1

  公开（公告）日：1996-05-15
• US5552404A
  申请人：——

  公开号：US5552404A

  公开（公告）日：1996-09-03