4-乙基-2-(3-甲基-4-硝基苯基)吗啉 | 1010384-74-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 中文名称: 4-乙基-2-(3-甲基-4-硝基苯基)吗啉
• 英文名称: 4-ethyl-2-(3-methyl-4-nitrophenyl)morpholine
• 英文别名: 4-Ethyl-2-(3-methyl-4-nitrophenyl)morpholine
• CAS: 1010384-74-3
• 化学式: C₁₃H₁₈N₂O₃
• 分子量: 250.298
• InChiKey: RWIFPJMUNOGACT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  58.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-乙基-2-(3-甲基-4-硝基苯基)吗啉 在 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 24.0h， 以62%的产率得到4-(4-ethylmorpholin-2-yl)-2-methylaniline
  参考文献：
  名称：

  Dopamine D3/D2 Receptor Antagonist PF-4363467 Attenuates Opioid Drug-Seeking Behavior without Concomitant D2 Side Effects

  摘要：

  Dopamine receptor antagonism is a compelling molecular target for the treatment of a range of psychiatric disorders, including substance use disorders. From our corporate compound file, we identified a structurally unique D3 receptor(D3R) antagonist scaffold, 1. Through a hybrid approach, we merged key pharmacophore elements from 1 and D3 agonist 2 to yield the novel D3R/D2R antagonist PE-4363467 (3). Compound 3 was designed to possess CNS drug-like properties as defined by its CNS MPO desirability score (>= 4/6). In addition to good physicochemical properties, 3 exhibited low nanomolar affinity for the D3R (D3 K-i = 3.1 nM), good subtype selectivity over D2R (D2 K-i = 692 nM), and high selectivity for D3R versus other biogenic amine receptors. In vivo, 3 dose-depeodentlye attenuated opioid self-administration and opioid drug-seeking, behavior in a rat operant reinstatement model using animals trained to self-administer fentanyl. Further,. traditional extrapyramidal symptoms (EPS), adverse side effects arising from D2R antagonism, were not observed despite high D2 receptor occupancy (RO) in rodents, suggesting that compound 3e has a unique in vivo profile. Collectively, our data support further investigation of dual D3R and D2R antagonists for the treatment of drug addiction.

  DOI：

  10.1021/acschemneuro.6b00297
• 作为产物：
  描述：

  3-甲基-4-硝基苯甲酰氯 在 三乙基硅烷 、 氢溴酸 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 89.5h， 生成 4-乙基-2-(3-甲基-4-硝基苯基)吗啉
  参考文献：
  名称：

  Dopamine D3/D2 Receptor Antagonist PF-4363467 Attenuates Opioid Drug-Seeking Behavior without Concomitant D2 Side Effects

  摘要：

  Dopamine receptor antagonism is a compelling molecular target for the treatment of a range of psychiatric disorders, including substance use disorders. From our corporate compound file, we identified a structurally unique D3 receptor(D3R) antagonist scaffold, 1. Through a hybrid approach, we merged key pharmacophore elements from 1 and D3 agonist 2 to yield the novel D3R/D2R antagonist PE-4363467 (3). Compound 3 was designed to possess CNS drug-like properties as defined by its CNS MPO desirability score (>= 4/6). In addition to good physicochemical properties, 3 exhibited low nanomolar affinity for the D3R (D3 K-i = 3.1 nM), good subtype selectivity over D2R (D2 K-i = 692 nM), and high selectivity for D3R versus other biogenic amine receptors. In vivo, 3 dose-depeodentlye attenuated opioid self-administration and opioid drug-seeking, behavior in a rat operant reinstatement model using animals trained to self-administer fentanyl. Further,. traditional extrapyramidal symptoms (EPS), adverse side effects arising from D2R antagonism, were not observed despite high D2 receptor occupancy (RO) in rodents, suggesting that compound 3e has a unique in vivo profile. Collectively, our data support further investigation of dual D3R and D2R antagonists for the treatment of drug addiction.

  DOI：

  10.1021/acschemneuro.6b00297

文献信息

• Dopamine D3/D2 Receptor Antagonist PF-4363467 Attenuates Opioid Drug-Seeking Behavior without Concomitant D2 Side Effects
  作者：Travis T. Wager、Thomas Chappie、David Horton、Ramalakshmi Y. Chandrasekaran、Brian Samas、Elizabeth R. Dunn-Sims、Cathleen Hsu、Nawshaba Nawreen、Michelle A. Vanase-Frawley、Rebecca E. O’Connor、Christopher J. Schmidt、Keith Dlugolenski、Nancy C. Stratman、Mark J. Majchrzak、Bethany L. Kormos、David P. Nguyen、Aarti Sawant-Basak、Andy N. Mead

  DOI：10.1021/acschemneuro.6b00297

  日期：2017.1.18

  Dopamine receptor antagonism is a compelling molecular target for the treatment of a range of psychiatric disorders, including substance use disorders. From our corporate compound file, we identified a structurally unique D3 receptor(D3R) antagonist scaffold, 1. Through a hybrid approach, we merged key pharmacophore elements from 1 and D3 agonist 2 to yield the novel D3R/D2R antagonist PE-4363467 (3). Compound 3 was designed to possess CNS drug-like properties as defined by its CNS MPO desirability score (>= 4/6). In addition to good physicochemical properties, 3 exhibited low nanomolar affinity for the D3R (D3 K-i = 3.1 nM), good subtype selectivity over D2R (D2 K-i = 692 nM), and high selectivity for D3R versus other biogenic amine receptors. In vivo, 3 dose-depeodentlye attenuated opioid self-administration and opioid drug-seeking, behavior in a rat operant reinstatement model using animals trained to self-administer fentanyl. Further,. traditional extrapyramidal symptoms (EPS), adverse side effects arising from D2R antagonism, were not observed despite high D2 receptor occupancy (RO) in rodents, suggesting that compound 3e has a unique in vivo profile. Collectively, our data support further investigation of dual D3R and D2R antagonists for the treatment of drug addiction.