N-(o-nitrophenyl)trimethylenediamine | 145315-42-0

• 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: N-(o-nitrophenyl)trimethylenediamine
• 英文别名: N-(o-nitrophenyl)-1,3-propanediamine；N₁-(2-nitrophenyl)propane-1,3-diamine；N-(2-nitrophenyl)propylenediamine；N-o-Nitrophenyl-trimethylen-1,3-diamin；N-(3-Aminopropyl)-2-nitrobenzenamine；N'-(2-nitrophenyl)propane-1,3-diamine
• CAS: 145315-42-0
• 化学式: C₉H₁₃N₃O₂
• mdl: MFCD00622907
• 分子量: 195.221
• InChiKey: GVGDDEYVTBKACE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  83.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(o-nitrophenyl)trimethylenediamine 在 sodium hydroxide 、 potassium carbonate 、 potassium iodide 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 15.0h， 生成 N-(2-nitrophenyl)propylenediamine-N',N'-diacetic acid
  参考文献：
  名称：

  用于Re（I）有机金属化学的新型乙二胺或丙二胺二乙酸衍生物的设计与合成

  摘要：

  已经开发出一种新的合成新型方法，用于“ fac- [M（CO）3 ] + ”核心（M = 99m Tc，99 Tc或Re）的新型双功能螯合剂（BCA）。该策略包括方便地制备具有叔胺的这些三齿配体，所述叔胺带有两个羧酸官能团作为配位位点和一个芳香族氨基基团以偶联至生物载体。首次络合研究表明，这些化合物仅充当三齿配体（通过两种酸和叔胺官能团）。这些新配体的便捷合成及其对Re（I）的高亲和力使它们在生物医学应用中非常有前途。

  DOI：

  10.1016/j.tet.2003.11.058
• 作为产物：
  描述：

  2-硝基苯胺 在 tetrafluoroboric acid 、 sodium nitrite 作用下， 生成 N-(o-nitrophenyl)trimethylenediamine
  参考文献：
  名称：

  Selective Small Molecules Blocking HIV-1 Tat and Coactivator PCAF Association

  摘要：

  Development of drug resistance from mutations in the targeted viral proteins leads to continuation of viral production by chronically infected cells, contributing to HIV-mediated immune dysfunction. Targeting a host cell protein essential for viral reproduction, rather than a viral protein, may minimize the viral drug resistance problem as observed with HIV protease inhibitors. We report here the development of a novel class of N1-aryl-propane-1,3-diamine compounds using a structure-based approach that selectively inhibit the activity of the bromodomain of the human transcriptional co-activator PCAF, of which association with the HIV trans-activator Tat is essential for transcription and replication of the integrated HIV provirus.

  DOI：

  10.1021/ja044885g

文献信息

• Atropisomerism in Amidinoquinoxaline <i>N-</i>Oxides: Effect of the Ring Size and Substituents on the Enantiomerization Barriers
  作者：Jimena E. Díaz、Nicolas Vanthuyne、Hélène Rispaud、Christian Roussel、Daniel Vega、Liliana R. Orelli

  DOI：10.1021/jo502626f

  日期：2015.2.6

  support. A clear ring size effect was evidenced. In all cases, six-membered amidine derivatives 1 showed higher barriers than the corresponding lower homologues 2, which also display lower sensitivity to the substituent size. Transition states for the interconversion of the atropisomers were located using DFT calculations, and involved the interaction of the ortho substituent with the formally sp2 nitrogen

  新型的带有不对称（邻位取代）5-芳基残基的2,3-二氢-1 H-嘧啶并[1,2 - a ]喹喔啉6-氧化物1和同源的1,2-二氢咪唑并[1,2-研究了α ]喹喔啉5-氧化物2。已证明化合物1a存在手性轴通过X射线衍射和基态几何的DFT计算。阻转异构体对映体在手性固定相上的拆分得到了报道。通过离线外消旋研究和/或在手性支持物色谱过程中通过处理平台形色谱图来确定对映异构化的障碍。明显的环尺寸效应被证明。在所有情况下，六元am衍生物1都比相应的较低同系物2表现出更高的势垒，后者对取代基的大小也表现出较低的敏感性。通过DFT计算确定了对映异构体互变的过渡态，并涉及邻位取代基与形式为sp 2的相互作用部分中的氮。相反，在2-硝基衍生物的最有利的对映异构转变状态下，邻位取代基接近于N-氧化物基团。
• An Efficient Synthesis of 2,3-Dihydro-1<i>H-</i>pyrimido[1,2-<i>a</i>]quinoxaline 6-Oxides
  作者：Isabel A. Perillo、María B. García、Liliana R. Orelli、María L. Magri

  DOI：10.1055/s-2002-35980

  日期：——

  5-Substituted 2,3-dihydro-1H-pyrimido[1,2-a]quinoxaline 6-oxides 1a-f were synthesized by ring closure of N-acyl-N′-(o-nitroaryl)-1,3-propanediamines 2 with ethyl polyphosphate (PPE) or trimethylsilyl polyphosphate (PPSE) to the corresponding 2-substituted 1-(o-nitroaryl)-1,4,5,6-tetrahydropyrimidines 3, followed by spontaneous heterocyclization. The method was extended to the synthesis of the homologous 6-aryl-1,2,3,4-tetrahydro-1,3-diazepino[1,2-a]quinoxaline 7-oxide (1g).

  5 取代的 2,3-二氢-1H-嘧啶并[1,2-a]喹喔啉 6-氧化物 1a-f 是通过 N-酰基-N′-（邻硝基芳基）-1、通过 N-酰基-N′-(邻硝基芳基)-1,4,5,6-四氢嘧啶 2 与多磷酸乙酯 (PPE) 或多磷酸三甲基硅酯 (PPSE) 的环闭合，合成相应的 2-取代 1-(邻硝基芳基)-1,4,5,6-四氢嘧啶 3，然后自发杂环化。 该方法还可用于合成同源的 6-芳基-1,2,3,4-四氢-1,3-二氮杂卓[1,2-a]喹喔啉 7-氧化物（1g）。
• Synthesis of 1-Aryl-1,4,5,6-tetrahydro-pyrimidines and 1-Aryl-3-substituted 1,4,5,6-Tetrahydropyrimidinium Salts
  作者：Isabel Perillo、Liliana R. Orelli、María B. García、Isabel A. Perillo

  DOI：10.3987/com-00-9018

  日期：——

  3-propanediamines (5) with trimethylsilyl polyphosphate (PPSE). Quaternization of compounds (1) with methyl (or ethyl) iodide led to the corresponding cyclic amidinium salts (2), while treatment of compound (1a) with 2,4-dinitrochlorobenzene yielded an open chain product resulting from hydrolysis of the salt. An alternative method was employed for the synthesis of 1-aryl-1,4,5,6-tetrahydropyrimidinium salts bearing

  描述了一种合成 1-芳基-1,4,5,6-四氢嘧啶 (1) 的方法，通过 N-芳基-N'-甲酰基-1,3-丙二胺 (5) 与三甲基甲硅烷基多磷酸盐 (PPSE) 的闭环. 用甲基（或乙基）碘对化合物（1）进行季铵化得到相应的环状脒盐（2），而用2,4-二硝基氯苯处理化合物（1a）得到由盐水解产生的开链产物。另一种方法用于合成在 N3 上带有支链烷基或芳基取代基的 1-芳基-1,4,5,6-四氢嘧啶盐，不能通过烷基化获得。通过相应的六氢嘧啶 (3) 的脱氢以高产率获得此类化合物。讨论了这两个程序的范围和限制。
• Amidinoquinoxaline N-oxides: spin trapping of O- and C-centered radicals
  作者：Nadia Gruber、Liliana R. Orelli、Roberto Cipolletti、Pierluigi Stipa

  DOI：10.1039/c7ob01387f

  日期：——

  Amidinoquinoxaline N-oxides represent a novel family of heterocyclic spin traps. In this work, their ability to trap O- and C-centered radicals was tested using selected derivatives with different structural modifications. All the studied nitrones were able to trap radicals forming persistent spin adducts, also in the case of OH and OOH radicals which are of wide biological interest as examples of ROS. The

  mid基喹喔啉N-氧化物代表杂环自旋捕集阱的新家族。在这项工作中，使用选定的具有不同结构修饰的衍生物测试了它们捕获O-和C-中心自由基的能力。所有研究过的硝酮都能够捕获形成持久性自旋加合物的自由基，同样在具有广泛生物学意义的OH和OOH自由基的情况下，例如ROS。加合物的稳定性主要归因于未配对电子在整个喹喔啉部分上的广泛离域。分析了氮氧化物光谱参数（hfccs和g因子），结果得到DFT计算的支持。N-19 hfcc和g因子是每个氨氧基的特征，可以帮助识别被困的自由基。在所采用的反应条件下，OH加合物稳定性的提高可能归因于具有两个不同受体的IHBs可能的稳定作用：N–O˙部分或am官能团。DFT计算表明，优选的IHB受到idine环大小的强烈调节。虽然五元同系物显示出对带有N–O˙基团的IHB的明显偏好，但在六元衍生物中，这种稳定的相互作用优先建立在以nitrogen氮作为IHB受体的情况下。
• Potent and Selective Inhibitors of Glutathione <i>S</i>-Transferase Omega 1 That Impair Cancer Drug Resistance
  作者：Katsunori Tsuboi、Daniel A. Bachovchin、Anna E. Speers、Timothy P. Spicer、Virneliz Fernandez-Vega、Peter Hodder、Hugh Rosen、Benjamin F. Cravatt

  DOI：10.1021/ja2066972

  日期：2011.10.19

  Glutathione S-transferases (GSTs) are a superfamily of enzymes that conjugate glutathione to a wide variety of both exogenous and endogenous compounds for biotransformation and/or removal. Glutathione S-tranferase omega 1 (GSTO1) is highly expressed in human cancer cells, where it has been suggested to play a role in detoxification of chemotherapeutic agents. Selective inhibitors of GSTO1 are, however, required to test the role that this enzyme plays in cancer and other (patho)physiological processes. With this goal in mind, we performed a fluorescence polarization activity-based protein profiling (fluopol-ABPP) high-throughput screen (HTS) with GSTO1 and the Molecular Libraries Small Molecule Repository (MLSMR) 300K+ compound library. This screen identified a class of selective and irreversible alpha-chloroacetamide inhibitors of GSTO1, which were optimized to generate an agent KT53 that inactivates GSTO1 with excellent in vitro (IC(50) =21 nM) and in situ (IC(50) = 35 nM) potency. Cancer cells treated with KT53 show heightened sensitivity to the cytotoxic effects of cisplatin, supporting a role for GSTO1 in chemotherapy resistance.