2-maleimidoethoxy N-t-Boc-glycinate | 158745-41-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-maleimidoethoxy N-t-Boc-glycinate
• 英文别名: 2-(2,5-Dioxopyrrol-1-yl)ethyl 2-[(2-methylpropan-2-yl)oxycarbonylamino]acetate
• CAS: 158745-41-6
• 化学式: C₁₃H₁₈N₂O₆
• 分子量: 298.296
• InChiKey: TWAJFUBBDGZTLZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-maleimidoethoxy N-t-Boc-glycinate 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  基于马来酰亚胺类似物开发强效且有效的 SARS-CoV-2 主要蛋白酶抑制剂，用于潜在治疗 COVID-19

  摘要：

  在目前的工作中，我们报告了一系列基于马来酰亚胺衍生物的新系列强效 SARS-CoV-2 主蛋白酶 (Mpro) 抑制剂。使用re...在酶测定中测试了抑制活性。

  DOI：

  10.1080/14756366.2023.2290910
• 作为产物：
  描述：

  N-(2-羟乙基)马来酰亚胺 在 2,6-二甲基吡啶 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 2-maleimidoethoxy N-t-Boc-glycinate
  参考文献：
  名称：

  Maleimidoethyl 3-(Tri-n-butylstannyl)hippurate: A Useful Radioiodination Reagent for Protein Radiopharmaceuticals To Enhance Target Selective Radioactivity Localization

  摘要：

  In pursuit of radiolabeled monoclonal antibodies (mAbs) with rapid urinary excretion of radioactivity from nontarget tissues, radioiodinated mAbs releasing a m-iodohippuric acid from the mAbs in nontarget tissues were designed. A novel reagent, maleimidoethyl 3-(tri-n-butylstannyl)hippurate (MIH), was synthesized by reacting N-(hydroxyethyl)maleimide with N-Boc-glycine before coupling with N-succinimidyl 3-(tri-n-butylstannyl)benzoate (ATE). MIH possessed a maleimide group for mAb conjugation and a butylstannyl moiety for high-yield and site-specific radioiodination, and the two functional groups were linked via an ester bond to release m-iodohippuric acid. To investigate the fate of radiolabels after lysosomal proteolysis, hepatic parenchymal cells were used as a model nontarget tissue and I-131-labeled MIH was conjugated with galactosyl-neoglycoalbumin (NGA). Further conjugation of[I-131]MIH with a mAb against osteogenic sarcoma (OST7) after reduction of its disulfide bonds was followed up. In murine biodistribution studies, [I-131]MIH-NGA exhibited rapid accumulation in the liver followed by radioactivity elimination from the liver at a rate that was identical to and faster than those of I-131-labeled NGA via direct iodination ([I-131]NGA) and [I-131]ATE-labeled NGA, respectively. While [I-131]NGA indicated high radioactivity levels in the murine neck, stomach, and blood, such increases in the radioactivity count were not detectable by the administration of either [I-131]MIH-NGA or [I-131]ATE-NGA. At 6 h postinjection of [I-131]MIH-NGA, 80% of the injected radioactivity was recovered in the urine. Analyses of urine samples indicated that m-iodohippuric acid was the sole radiolabeled metabolite. In biodistribution studies using [I-131]MIH-OST7 and [I-131]ATE-OST7, while both I-131-labeled OST7s registered almost identical radioactivity levels in the blood up to 6 h postinjection, the former demonstrated a lower radioactivity level than [I-131]ATE-OST7 in nontarget tissues throughout the experiment. Such chemical and biological characteristics of MIH would enable high target/nontarget ratios in diagnostic and therapeutic nuclear medicine using mAbs and other polypeptides.

  DOI：

  10.1021/jm00042a014

文献信息

• Maleimidoethyl 3-(Tri-n-butylstannyl)hippurate: A Useful Radioiodination Reagent for Protein Radiopharmaceuticals To Enhance Target Selective Radioactivity Localization
  作者：Yasushi Arano、Kouji Wakisaka、Yoshiro Ohmomo、Takashi Uezono、Takahiro Mukai、Hiroshi Motonari、Hiromitsu Shiono、Harumi Sakahara、Junji Konishi

  DOI：10.1021/jm00042a014

  日期：1994.8

  In pursuit of radiolabeled monoclonal antibodies (mAbs) with rapid urinary excretion of radioactivity from nontarget tissues, radioiodinated mAbs releasing a m-iodohippuric acid from the mAbs in nontarget tissues were designed. A novel reagent, maleimidoethyl 3-(tri-n-butylstannyl)hippurate (MIH), was synthesized by reacting N-(hydroxyethyl)maleimide with N-Boc-glycine before coupling with N-succinimidyl 3-(tri-n-butylstannyl)benzoate (ATE). MIH possessed a maleimide group for mAb conjugation and a butylstannyl moiety for high-yield and site-specific radioiodination, and the two functional groups were linked via an ester bond to release m-iodohippuric acid. To investigate the fate of radiolabels after lysosomal proteolysis, hepatic parenchymal cells were used as a model nontarget tissue and I-131-labeled MIH was conjugated with galactosyl-neoglycoalbumin (NGA). Further conjugation of[I-131]MIH with a mAb against osteogenic sarcoma (OST7) after reduction of its disulfide bonds was followed up. In murine biodistribution studies, [I-131]MIH-NGA exhibited rapid accumulation in the liver followed by radioactivity elimination from the liver at a rate that was identical to and faster than those of I-131-labeled NGA via direct iodination ([I-131]NGA) and [I-131]ATE-labeled NGA, respectively. While [I-131]NGA indicated high radioactivity levels in the murine neck, stomach, and blood, such increases in the radioactivity count were not detectable by the administration of either [I-131]MIH-NGA or [I-131]ATE-NGA. At 6 h postinjection of [I-131]MIH-NGA, 80% of the injected radioactivity was recovered in the urine. Analyses of urine samples indicated that m-iodohippuric acid was the sole radiolabeled metabolite. In biodistribution studies using [I-131]MIH-OST7 and [I-131]ATE-OST7, while both I-131-labeled OST7s registered almost identical radioactivity levels in the blood up to 6 h postinjection, the former demonstrated a lower radioactivity level than [I-131]ATE-OST7 in nontarget tissues throughout the experiment. Such chemical and biological characteristics of MIH would enable high target/nontarget ratios in diagnostic and therapeutic nuclear medicine using mAbs and other polypeptides.
• Development of potent and effective SARS-CoV-2 main protease inhibitors based on maleimide analogs for the potential treatment of COVID-19
  作者：Karol Biernacki、Olga Ciupak、Mateusz Daśko、Janusz Rachon、Damian Flis、Justyna Budka、Iwona Inkielewicz-Stępniak、Anna Czaja、Janusz Rak、Sebastian Demkowicz

  DOI：10.1080/14756366.2023.2290910

  日期：2024.12.31

  In the present work, we report a new series of potent SARS-CoV-2 Main Protease (Mpro) inhibitors based on maleimide derivatives. The inhibitory activities were tested in an enzymatic assay using re...

  在目前的工作中，我们报告了一系列基于马来酰亚胺衍生物的新系列强效 SARS-CoV-2 主蛋白酶 (Mpro) 抑制剂。使用re...在酶测定中测试了抑制活性。