2-Diazo-1-(3-methyl-4-nitro-phenyl)-ethanone | 206874-44-4

• 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: 2-Diazo-1-(3-methyl-4-nitro-phenyl)-ethanone
• CAS: 206874-44-4
• 化学式: C₉H₇N₃O₃
• 分子量: 205.173
• InChiKey: LJRFGHRCSXEGDO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.39
• 重原子数：
  15.0
• 可旋转键数：
  3.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  96.61
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  2-Diazo-1-(3-methyl-4-nitro-phenyl)-ethanone 在 palladium on activated charcoal lithium aluminium tetrahydride 、 氯化亚砜 、 氢气 、 碳酸氢钠 、 sodium thiosulfate 、 1-羟基苯并三唑一水物 、 N,N'-二环己基碳二亚胺 、 silver(l) oxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 25.0~80.0 ℃ 、101.33 kPa 条件下， 反应 15.0h， 生成 N-[2-Methyl-4-[2-[[(3,4-dimethoxyphenyl)methyl]methylamino]ethyl]phenyl]-9,10-dihydro-5-methyl-9-oxo-4-acridinecarboxamide
  参考文献：
  名称：

  Synthesis and Activity against Multidrug Resistance in Chinese Hamster Ovary Cells of New Acridone-4-carboxamides

  摘要：

  A number of tricyclic carboxamides have been synthesized and tested to evaluate their ability to reverse multidrug resistance in the (CHC)-C-R/5 cell line. Among them the acridone derivatives were the most potent, A key feature is the presence of a dimethoxybenzyl or phenethylamine cationic site, separated from the tricyclic lipophilic part by a carbamoylphenyl chain. Optimization led to compounds 2 orders of magnitude more active than the prototype inhibitors verapamil and amiodarone. On the basis of in vitro and in vivo activities, 9,10-dihydro-5-methoxy- 9-oxo-N-[4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxyisoquinol-2-yl)ethyl]phenyl]-4-acridinecarboxamide (84) has been selected for further development.

  DOI：

  10.1021/jm00013a017
• 作为产物：
  描述：

  3-甲基-4-硝基苯甲酸 在 氯化亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 正己烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 15.0h， 生成 2-Diazo-1-(3-methyl-4-nitro-phenyl)-ethanone
  参考文献：
  名称：

  作为有效的口服活性VLA-4拮抗剂的苯甲酸衍生物的合成和生物学评估。

  摘要：

  合成了一系列苯甲酸衍生物作为VLA-4拮抗剂。如铅化合物2中那样，将氯或溴引入到二苯基脲部分的中心苯的3-位上导致药代动力学性质的改善。特别地，12l在小鼠和大鼠以及狗中表现出可接受的血浆清除率和生物利用度（小鼠，CL = 18.5 ml / min / kg，F = 28％；大鼠，CL = 5.2 ml / min / kg，F = 36 ％；狗，CL ＝ 3.6ml / min / kg，F ＝ 55％）。另外，在大鼠胸膜炎模型中，以10mg / kg的剂量口服给药时，12μl显示出有效的活性，IC50值为0.51nM，并且具有功效。

  DOI：

  10.1016/j.bmc.2006.12.006

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.