(+)-3-((αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)benzonitrile | 155836-83-2

• 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)benzonitrile
• 英文别名: (+/-)-3-((alphaR*)-alpha-((2S*,5R*)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)benzonitrile；3-[(R)-[(2S,5R)-2,5-dimethyl-4-prop-2-enylpiperazin-1-yl]-(3-hydroxyphenyl)methyl]benzonitrile
• CAS: 155836-83-2
• 化学式: C₂₃H₂₇N₃O
• 分子量: 361.487
• InChiKey: PDIUVGYASOBOAV-IEGUWTFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  50.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+)-3-((αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)benzonitrile 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 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 97.5h， 生成 DPI-3290
  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
• 作为产物：
  描述：

  α-(3-bromophenyl)-3-(tert-butyldimethylsilyloxy)-benzyl alcohol 在 氯化亚砜 、 四乙基氟化铵水合物 作用下， 以 N-甲基吡咯烷酮 、 二氯甲烷 、 乙腈 为溶剂， 反应 79.0h， 生成 (+)-3-((αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)benzonitrile
  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 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.

  具有作为外源受体结合物种的作用的二芳基甲基哌嗪化合物，用于与δ、μ、σ和/或κ受体结合的目的。本发明的化合物可作为激动剂/拮抗剂对在神经递质功能的传导监测和测定中使用，并且具有各种治疗用途，包括介导镇痛，以及用于治疗腹泻、尿失禁、精神疾病、药物和酒精成瘾/过量服用、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。
• Compositions and Methods for Reducing Respiratory Depression and Attendant SIde Effects of Mu Opioid Compounds
  申请人：Ardent Pharmaceuticals, Inc.

  公开号：US20020111359A1

  公开（公告）日：2002-08-15

  Abstract of Disclosure 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.

  披露摘要：一种减少、治疗或预防动物中药物介导的呼吸抑制、肌肉僵硬或恶心/呕吐的方法，涉及向接受混合δ/μ阿片受体激动剂或呼吸抑制药物的动物施用有效量的δ受体激动剂化合物。此类δ受体激动剂化合物的优选示例包括二苯甲基哌嗪化合物和二苯甲基哌啶化合物，以及具有医疗疗效的药物组合物，可用于减少与某些镇痛药物（如μ阿片类药物）相关的呼吸抑制。
• 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.

  披萨辣椒酱含有辣椒、番茄、大蒜、洋葱、橄榄油和香料等原料，口感香辣可口，适合搭配披萨、意面、三明治等食物一起食用。
• [EN] OPIOID DIARYLMETHYLPIPERAZINES AND PIPERIDINES
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：WO1993015062A1

  公开（公告）日：1993-08-05

  (EN) Diarylmethyl piperazine/piperidine compounds of formula (I) as shown above wherein the substituents are as defined in the description having utility as exogenous receptor combinant species for binding with receptors such as delta, mu, sigma, and/or kappa receptors. 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, and apnea, cognitive disorders, and gastrointestinal disorders.(FR) Composés de pipérazine/pipéridine de diarylméthyle répondant à la formule (I), où les substituants sont définis dans le descriptif, ces composés pouvant servir comme espèces de combinaison de récepteurs exogènes pouvant être liés à des récepteurs tels que les récepteurs delta, mu, sigma et/ou kappa. Les composés de cette invention peuvent être utilisés comme conjugués dans des paires agonistes/antagonistes pour les dosages et la surveillance par transduction de la fonction de neurotransmetteur, et présentent également une utilité thérapeutique, y compris pour induire l'analgésie, ainsi que pour le traitement des diarrhées, de l'incontinence urinaire, des maladies mentales, de l'overdose et de l'accoutumance à la drogue et à l'alcool, des ÷dèmes du poumon, de la dépression, de l'asthme, des emphysèmes et de l'apnée, des troubles cognitifs et des troubles gastro-intestinaux.

  （中文翻译）上述式子中的Diarylmethyl piperazine/piperidine化合物，其中取代基如描述中所定义，具有作为外源性受体组合物种类的实用性，可与Delta、Mu、Sigma和/或Kappa受体结合。本发明的化合物可作为激动剂/拮抗剂对在神经递质功能的转导监测和测定中使用，并且也具有各种治疗用途，包括调节镇痛作用，以及用于治疗腹泻、尿失禁、精神疾病、药物和酒精成瘾/过量、肺水肿、抑郁症、哮喘、肺气肿和呼吸暂停、认知障碍和胃肠疾病。
• Compositions and methods for reducing respiratory depression and attendant side effects of mu opioid compounds
  申请人：Chang Kwen-Jen

  公开号：US20050255151A1

  公开（公告）日：2005-11-17

  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.

  本发明涉及一种减少、治疗或预防动物在接受混合的delta/mu阿片类激动剂或呼吸抑制介导药物时出现的呼吸抑制、肌肉僵硬或恶心/呕吐的方法，包括向接受该药物的动物投与有效剂量的delta受体激动剂化合物。这种delta受体激动剂化合物的优选例子包括二芳基甲基哌嗪化合物和二芳基甲基哌啶化合物，以及其制药组合物，在医疗治疗中用于减轻与某些镇痛药物（如mu阿片类药物）相关的呼吸抑制。