DPI-3290 | 182417-73-8

• 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: DPI-3290
• 英文别名: (+)-3-((alpha-R)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-(3-fluorophenyl)-N-methylbenzamide；(+)-3-((αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-(3-fluorophenyl)-N-methylbenzamide；3-[(R)-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)(3-hydroxyphenyl)methyl]-N-(3-fluorophenyl)-N-methylbenzamide；(+)-3-((alphaR)-alpha-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-hydroxybenzyl)-N-(3-fluorophenyl)-N-methylbenzamide；3-[(R)-[(2S,5R)-2,5-dimethyl-4-prop-2-enylpiperazin-1-yl]-(3-hydroxyphenyl)methyl]-N-(3-fluorophenyl)-N-methylbenzamide
• CAS: 182417-73-8
• 化学式: C₃₀H₃₄FN₃O₂
• 分子量: 487.617
• InChiKey: LZXRQLIIMYJZDA-UETOGOEVSA-N

物化性质

• 熔点：
  144-145 °C
• 沸点：
  620.4±55.0 °C(Predicted)
• 密度：
  1.161±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  47
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 储存条件：
  2-8°C

制备方法与用途

生物活性

DPI-3290 (Org 41793) 是一种有效的、特异性的阿片受体激动剂，对 δ-、μ- 和 κ- 阿片受体的 Ki 值分别为 0.18 nM、0.46 nM 和 0.62 nM。它属于一系列新型中枢作用药物，具有强烈的抗伤害作用。

靶点

• IC50: 0.18 nM (δ-阿片受体)，0.46 nM (μ-阿片受体) 和 0.62 nM (κ-阿片受体)

体内研究

DPI-3290 (Org 41793) 在静脉注射 (intravenous; 0.05 mg/kg) 后，可使大鼠产生约 50% 的镇痛反应。

反应信息

• 作为反应物：
  描述：

  DPI-3290 在 ammonium hydroxide 、 三氯氧磷 作用下， 以 吡啶 、 水 、 丙酮 为溶剂， 生成 3-((R)-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-(N-(3-fluorophenyl)-N-methylcarbamoyl)benzyl)phenyl monophosphate
  参考文献：
  名称：

  Opioid compounds and methods for using same

  摘要：

  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。

  公开号：

  US05552404A1
• 作为产物：
  描述：

  在 四乙基氟化铵水合物 作用下， 以 乙腈 为溶剂， 反应 1.0h， 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

文献信息

• Method of treating sexual dysfunctions with delta opioid receptor agonist compounds
  申请人：——

  公开号：US20030186872A1

  公开（公告）日：2003-10-02

  Compositions and methods for treatment of sexual dysfunctions by administering to a subject a pharmaceutical composition comprising a delta opioid receptor agonist in an amount effective to delay the onset of ejaculation in the subject during sexual stimulation.

  通过向受试者施用含有δ阿片受体激动剂的药物组合物，以延迟受试者在性刺激过程中射精的发生，用于治疗性功能障碍的组合物和治疗方法。
• Compositions and methods for combating lower urinary tract dysfunctions with delta opioid receptor agonists
  申请人：——

  公开号：US20040002503A1

  公开（公告）日：2004-01-01

  Compositions and methods for treatment of a urinary tract dysfunction by administering to a subject in need of such treatment a pharmaceutical composition including a delta opioid receptor agonist in an amount effective to reduce the effects of the urinary tract dysfunction. The compositions may further include an additional active agent that is used to treat urinary tract dysfunctions, e.g., alpha-adrenergic agonists, anticholinergics, alpha-adrenergic antagonists and tricyclic antidepressants.

  通过向需要此类治疗的受试者施用包括δ阿片受体激动剂的药物组合物，以减少尿路功能障碍的影响的方法和组合物。这些组合物还可以进一步包括用于治疗尿路功能障碍的其他活性药物，例如α-肾上腺素受体激动剂、抗胆碱药、α-肾上腺素受体拮抗剂和三环抗抑郁药。
• [EN] AN OPIOID FOR USE TO REDUCE AND/OR TREAT DRUG ADDICTION<br/>[FR] OPIOÏDE DESTINÉ À ÊTRE UTILISÉ POUR RÉDUIRE ET/OU TRAITER LA PHARMACODÉPENDANCE
  申请人：VERSI GROUP LLC

  公开号：WO2018204163A1

  公开（公告）日：2018-11-08

  The present invention relates to a method of treating drug addiction and reducing dependence or tolerance on a dependence-inducing opiate drug, wherein the method comprises administering to a subject a compound having the structure of formula (I): having the IUPAC name of (-)3-((S)-((2S,5R)-4-allyl-2,5-dimethyl-l-piperazinyl)(3-thienyl)methyl)phenol, or pharmaceutically acceptable esters or salts thereof, wherein the compound has activity on the mu, delta and kappa opioid receptors thereby providing added analgesia with an improved therapeutic index and reduced risk of respiratory depression.

  本发明涉及一种治疗药物成瘾、减少对诱导依赖的鸦片类药物的依赖或耐受性的方法，其中该方法包括向受试者施用具有以下公式（I）结构的化合物：(-)3-((S)-((2S,5R)-4-烯丙基-2,5-二甲基-1-哌嗪基)(3-噻吩基)甲基)苯酚的IUPAC名称，或其药学上可接受的酯或盐，化合物对mu、delta和kappa阿片受体具有活性，从而提供具有改善的治疗指数和减少呼吸抑制风险的附加镇痛作用。
• [EN] METHOD OF TREATING SEXAUAL DYSFUNCTIONS WITH DELTA OPIOID RECEPTOR AGONIST COMPOUNDS<br/>[FR] METHODE DE TRAITEMENT DE DYSFONCTIONS SEXUELLES AU MOYEN DE COMPOSES D'AGONISTE DU RECEPTEUR DELTA OPIOIDE
  申请人：ARDENT PHARMACEUTICALS INC

  公开号：WO2003057223A1

  公开（公告）日：2003-07-17

  Compositions and methods for treatment of sexual dysfunctions by administering to a subject a pharmaceutical composition comprising a delta opioid receptor agonist in an amount effective to delay the onset of ejaculation in the subject during sexual stimulation.

  本发明涉及一种通过给予患者含有δ-阿片受体激动剂的药物组合物来治疗性功能障碍的方法。在性刺激期间，该药物组合物的有效剂量可以延迟患者射精的开始。
• Diarylmethylbenzylpiperazines and corresponding halobenzyl derivatives
  申请人：——

  公开号：US20020052007A1

  公开（公告）日：2002-05-02

  Diarylmethylbenzylpiperazine compounds, optionally substituted on an aromatic ring of the benzyl substituent with one or more halo substituents, and pharmaceutically acceptable esters and salts of such compounds. Such compounds are usefully employed in therapeutic intervention for treatment or prophylaxis of disease states and conditions such as drug addiction, alcohol addiction, drug overdose, mental illness, cough, lung edema, gastro-intestinal disorders, arthritis, psoriasis, asthma, inflammatory bowel disease, disorders of respiratory function, functional bowel disease, irritable bowel syndrome, diarrhea, functional distension, pain (e.g., functional pain, trauma pain, etc.), non-ulcerogenic dyspepsia, urogenital tract disorders, organ transplant rejection, skin graft rejection, mental disorders, cognitive disorders, emesis, respiratory depression, acne and skin lesions. One preferred compound of such type is 1 or a pharmaceutically acceptable ester or salt thereof.

  Diarylmethylbenzylpiperazine化合物，可选地在苯甲基取代基的芳香环上用一个或多个卤素取代基进行取代，并且这种化合物的药物学上可接受的酯和盐。这些化合物可用于治疗或预防疾病状态和病情，如药物成瘾，酒精成瘾，药物过量，精神疾病，咳嗽，肺水肿，胃肠疾病，关节炎，牛皮癣，哮喘，炎症性肠病，呼吸功能障碍，功能性肠病，肠易激综合征，腹泻，功能性胀气，疼痛（例如功能性疼痛，创伤性疼痛等），非溃疡性消化不良，泌尿生殖道疾病，器官移植排斥，皮肤移植排斥，精神障碍，认知障碍，呕吐，呼吸抑制，痤疮和皮肤病变。这种类型的一个优选化合物是1或其药物学上可接受的酯或盐。