1-(1',3'-dioxyl-4',4',5',5'-tetramethyldihydroimidazol-2'-yl)-phenyl-4-yloxylacetic ethyl ester | 642097-77-6

• 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: 1-(1',3'-dioxyl-4',4',5',5'-tetramethyldihydroimidazol-2'-yl)-phenyl-4-yloxylacetic ethyl ester
• 英文别名: 2-(4'-(ethoxycarbonylmethoxy)phenyl)-4,4,5,5-tetramethylimidazolidine-3-oxide-1-oxyl
• CAS: 642097-77-6
• 化学式: C₁₇H₂₃N₂O₅
• 分子量: 335.38
• InChiKey: BVFNJYQFFGLKKN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  68.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(1',3'-dioxyl-4',4',5',5'-tetramethyldihydroimidazol-2'-yl)-phenyl-4-yloxylacetic ethyl ester 在 sodium hydroxide 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 48.5h， 生成 N-[1-(1',3'-dioxyl-4',4',5',5'-tetramethyldihydroimidazol-2-yl)phenyl-4-yl]oxyacetyl-Gln-Arg(Tos)-Pro-Ala-Lys(Z)-OBzl
  参考文献：
  名称：

  Synthesis and Biological Activity of Nitronyl Nitroxide Containing Peptides

  摘要：

  [1-(1 ',3 '-Dioxyl-4 ',4 ',5 ',5 '-tetramethyldihydroimidazol-2-yl)-phenyl-4-yl]oxyacetic acid (4), a nitronyl nitroxide, and its peptide derivatives, N-[1-(1 ',3 '-dioxyl-4 ',4 ',5 ',5 '-tetramethyldihydroimidazol-2-yl)-phenyl-4-yl]oxyacetyl-ARPAK (9a), -GRPAK (9b), and -QRPAK (9c), were synthesized and characterized. Judging from the results of electron spin resonance analysis, the newly synthesized nitronyl nitroxide containing peptides, 9a, 9b, and 9c, demonstrated the characteristics of free radicals. The free radical scavenging activities of 9a, 9b, and 9c were assessed using in vitro free radical scavenging tests. The thrombolysis effect of 9a, 9b, and 9c was evaluated using an euglobulin clot lysis test, a fibrinolytic lysis test, and in vivo thrombolysis tests. Results indicated that these nitronyl nitroxide containing peptides possessed both free radical scavenging activity and thrombolytic activity.

  DOI：

  10.1021/jm050050k
• 作为产物：
  描述：

  2,3-二甲基-2,3-二硝基丁烷 在 sodium ethanolate 、 氯化铵 、 lead dioxide 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 28.0h， 生成 1-(1',3'-dioxyl-4',4',5',5'-tetramethyldihydroimidazol-2'-yl)-phenyl-4-yloxylacetic ethyl ester
  参考文献：
  名称：

  作为自由基清除剂的新型2-取代硝酰基硝基氧化合物：合成，生物学评估和结构-活性关系。

  摘要：

  为了开发具有增强的自由基清除剂性能的更有效的小分子，我们设计并合成了一系列硝酰基硝基氧衍生物4a-h。基于Ach诱导的血管舒张测定法发现了前导化合物4f。基于该支架的进一步化学修饰提供了一系列新的2-取代的苯基亚硝酰基硝基氧化物衍生物6a-s。基于PC12细胞存活测定法，新合成的化合物6a-s具有改善的自由基清除剂的活性。就NO，H（2）O（2）和OH的清除能力而言，化合物6g，n，o和s是一些最有效的化合物。2-取代的苯基亚硝基硝基氮氧化物具有较高的自由基清除活性，带有给电子基团（EDG）。相比之下，吸电子基团（EWG）引入芳环导致其自由基清除活性急剧下降。这些结果表明，芳香环的给电子基团（EDG）可能是影响这些化合物清除自由基行为的重要因素，清除自由基的能力很大程度上取决于苯环的位置和电子性质。取代基。新型的2-取代的硝酰基氮氧化物的增强的自由基清除能力可能是对抗ROS（活性氧）/ R

  DOI：

  10.1016/j.bmc.2006.04.016

文献信息

• A class of novel nitronyl nitroxide labeling basic and acidic amino acids: Synthesis, application for preparing ESR optionally labeling peptides, and bioactivity investigations
  作者：Jianwei Zhang、Ming Zhao、Guohui Cui、Shiqi Peng

  DOI：10.1016/j.bmc.2008.01.022

  日期：2008.4.1

  beta-carboxyl of L-Asp-OH and the gamma-carboxyl of L-Glu-OH with ethylamino as a linker. It was explored that the synthetic 30 novel ESR labeling amino acid derivatives were stable enough to the reaction conditions of peptide synthesis. Their incorporation led to 12 novel ESR optionally labeling PAK, RGDS, RGDV, and ECG. A series of NO related chemical tests, the in vitro and in vivo assays of these

  瞄准任选的ESR标记，将2-（4'-羟基）苯基-4,4,5,5-四甲基咪唑啉-3-氧化物-1-氧基引入到L-Arg-OH的胍基中，以甲基羧基为连接基的L-Lys-OH，和以乙氨基为连接基的L-Asp-OH的β-羧基和L-Glu-OH的γ-羧基。研究表明，合成的30种新型ESR标记氨基酸衍生物对肽合成的反应条件足够稳定。他们的加入导致了12种新颖的ESR，可选地标记了PAK，RGDS，RGDV和ECG。一系列与NO相关的化学测试，这些肽的体外和体内测定证实了该策略是可行的。
• NOVEL COMPOUND WITH EFFECTS OF THROMBOLYSIS, FREE RADICAL SCAVENGING AND THROMBUS-TARGETING AS WELL AS PREPARATION METHOD AND USE THEREOF
  申请人：Shanghai Lumosa Therapeutics, Co., Ltd.

  公开号：US20150290339A1

  公开（公告）日：2015-10-15

  The present invention discloses a novel compound with effects of thrombolysis, free radical scavenging and thrombus-targeting, as well as a preparation method and use thereof. The compound is a ternary conjugate formed by conjugating a thrombolytic peptide, a free radical scavenger and a thrombus-targeting/antithrombotic peptide together via a linking arm. The present invention also discloses a pharmaceutical composition containing the compounds, wherein the compounds form a nanospherical structure.

  本发明公开了一种具有溶栓、清除自由基和靶向血栓作用的新型化合物，以及其制备方法和用途。该化合物是通过连接臂将溶栓肽、自由基清除剂和靶向/抗血栓肽结合在一起形成的三元共轭物。本发明还公开了含有这些化合物的药物组合物，其中这些化合物形成纳米球状结构。
• Protective effect of nitronyl nitroxide–amino acid conjugates on liver ischemia–reperfusion induced injury in rats
  作者：Wei Bi、Jianhui Cai、Ping Xue、Yanrong Zhang、Sanguang Liu、Xiang Gao、Meng Li、Zhibo Wang、Michèle Baudy-Floc’h、Sarah A. Green、Lanrong Bi

  DOI：10.1016/j.bmcl.2008.02.030

  日期：2008.3

  Stable nitroxides are potential antioxidant drugs. In this study, we have linked nitroxide to natural amino acids with the aim to improve therapeutic activity. The radical scavenging activities of two nitronyl nitroxide - amino acid conjugates ( NNR and NNK) were evaluated in PC 12 cell survival assays. The NO scavenging activities of these compounds were confirmed in the acetylcholine-induced vasorelaxation assay. In addition, the protective effect of NNR was demonstrated in an in vivo rat model of hepatic ischemia - reperfusion ( I/ R) induced injury and oxidative change. Because NNR reduced hepatic I/ R injury by minimizing oxidative stress, it might be possible to develop it into a possible therapeutic agent for hepatic I/ R injury. (C) 2008 Elsevier Ltd. All rights reserved.
• Synthesis and bioactivities of nitronyl nitroxide and RGD containing pseudopeptides
  作者：Junling Liu、Ming Zhao、Chao Wang、Shiqi Peng

  DOI：10.1016/j.bmcl.2003.08.041

  日期：2003.11

  1-(1',3'-Dioxyl-4',4',5',5'-tetramethyldihydroimidazol-2'-yl)-phenyl-4-yloxylacetic acid (3), and 1-(1',3'-dioxyl-4',4',5',5'-tetramethyldihydroimidazol-2'-yl)-phenyl-4-yloxylacetyl-RGDS (13), -RGDV (14), -RGDF (15) were synthesized. The ESR measurement gave the same spectroscopy for 3 and 13-15. The NO scavenging tests in vitro, anti-platelet aggregation tests in vitro and the anti-thrombosis assay in vivo indicated that introducing 3 into the N-terminal of RGDS, RGDV and RGDF the corresponding bioactivities for both of 3 and RGD peptides can be remained completely. The present combinations provided a beneficial strategy for simultaneous scavenging NO and anti-thrombosis, and for the use of spin label of RGD peptides in the conformational researches. (C) 2003 Elsevier Ltd. All rights reserved.
• Synthesis and Biological Activity of Nitronyl Nitroxide Containing Peptides
  作者：Ming Zhao、Junling Liu、Chao Wang、Lili Wang、Hu Liu、Shiqi Peng

  DOI：10.1021/jm050050k

  日期：2005.6.1

  [1-(1 ',3 '-Dioxyl-4 ',4 ',5 ',5 '-tetramethyldihydroimidazol-2-yl)-phenyl-4-yl]oxyacetic acid (4), a nitronyl nitroxide, and its peptide derivatives, N-[1-(1 ',3 '-dioxyl-4 ',4 ',5 ',5 '-tetramethyldihydroimidazol-2-yl)-phenyl-4-yl]oxyacetyl-ARPAK (9a), -GRPAK (9b), and -QRPAK (9c), were synthesized and characterized. Judging from the results of electron spin resonance analysis, the newly synthesized nitronyl nitroxide containing peptides, 9a, 9b, and 9c, demonstrated the characteristics of free radicals. The free radical scavenging activities of 9a, 9b, and 9c were assessed using in vitro free radical scavenging tests. The thrombolysis effect of 9a, 9b, and 9c was evaluated using an euglobulin clot lysis test, a fibrinolytic lysis test, and in vivo thrombolysis tests. Results indicated that these nitronyl nitroxide containing peptides possessed both free radical scavenging activity and thrombolytic activity.