(N-(1'-methoxycarbonyl-ethyl)-carboxamido)-pyrazine | 73058-31-8

• 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: (N-(1'-methoxycarbonyl-ethyl)-carboxamido)-pyrazine
• 英文别名: methyl (pyrazine-2-carbonyl)-L-alaninate；(S)-N-Pyrazinoyl-methylalanat；N-(pyrazine-2-carbonyl)-alanine methyl ester；L-Alanine, N-(pyrazinylcarbonyl)-, methyl ester；methyl (2S)-2-(pyrazine-2-carbonylamino)propanoate
• CAS: 73058-31-8
• 化学式: C₉H₁₁N₃O₃
• 分子量: 209.205
• InChiKey: PULVOMQQBGMXGZ-LURJTMIESA-N

物化性质

• 沸点：
  424.0±35.0 °C(Predicted)
• 密度：
  1.233±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  81.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (N-(1'-methoxycarbonyl-ethyl)-carboxamido)-pyrazine 在 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 3.0h， 生成 N-(pyrazinecarbonyl)-L-alanine
  参考文献：
  名称：

  Chemical and Biological Evaluation of Dipeptidyl Boronic Acid Proteasome Inhibitors for Use in Prodrugs and Pro-Soft Drugs Targeting Solid Tumors

  摘要：

  Bortezomib, a dipeptidyl boronic acid and potent inhibitor of the 26S proteasome, is remarkably effective against multiple myeloma (MM) but not against solid tumors. Dose-limiting adverse effects from "on target" inhibition of the proteasome in normal cells and tissues appear to be a key obstacle. Achieving efficacy against solid tumors therefore is likely to require making the inhibitor more selective for tumor tissue over normal tissues. The simplest strategy that might provide such tissue specificity would be to employ a tumor specific protease to release an inhibitor from a larger, noninhibitory structure. However, such release would necessarily generate an inhibitor with a free N-terminal amino group, raising a key question: Can short peptide boronic acids with N-terminal amino groups have the requisite properties to serve as warheads in prodrugs? Here we show that dipeptides of boroLeu, the smallest plausible candidates for the task, can indeed be sufficiently potent, cell-penetrating, cytotoxic, and stable to degradation by cellular peptidases to serve in this capacity.

  DOI：

  10.1021/jm200460q
• 作为产物：
  描述：

  2-甲酸吡嗪 、 3-酞酰亚胺基丙酸甲酯 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (N-(1'-methoxycarbonyl-ethyl)-carboxamido)-pyrazine
  参考文献：
  名称：

  Chemical and Biological Evaluation of Dipeptidyl Boronic Acid Proteasome Inhibitors for Use in Prodrugs and Pro-Soft Drugs Targeting Solid Tumors

  摘要：

  Bortezomib, a dipeptidyl boronic acid and potent inhibitor of the 26S proteasome, is remarkably effective against multiple myeloma (MM) but not against solid tumors. Dose-limiting adverse effects from "on target" inhibition of the proteasome in normal cells and tissues appear to be a key obstacle. Achieving efficacy against solid tumors therefore is likely to require making the inhibitor more selective for tumor tissue over normal tissues. The simplest strategy that might provide such tissue specificity would be to employ a tumor specific protease to release an inhibitor from a larger, noninhibitory structure. However, such release would necessarily generate an inhibitor with a free N-terminal amino group, raising a key question: Can short peptide boronic acids with N-terminal amino groups have the requisite properties to serve as warheads in prodrugs? Here we show that dipeptides of boroLeu, the smallest plausible candidates for the task, can indeed be sufficiently potent, cell-penetrating, cytotoxic, and stable to degradation by cellular peptidases to serve in this capacity.

  DOI：

  10.1021/jm200460q

文献信息

• Amide Synthesis by Nickel/Photoredox‐Catalyzed Direct Carbamoylation of (Hetero)Aryl Bromides
  作者：Nurtalya Alandini、Luca Buzzetti、Gianfranco Favi、Tim Schulte、Lisa Candish、Karl D. Collins、Paolo Melchiorre

  DOI：10.1002/anie.202000224

  日期：2020.3.23

  Herein, we report a one‐electron strategy for catalytic amide synthesis that enables the direct carbamoylation of (hetero)aryl bromides. This radical cross‐coupling approach, which is based on the combination of nickel and photoredox catalysis, proceeds at ambient temperature and uses readily available dihydropyridines as precursors of carbamoyl radicals. The method's mild reaction conditions make

  在本文中，我们报告了一种催化酰胺合成的单电子策略，该策略可实现（杂）芳基溴化物的直接氨基甲酰基化。这种自由基交叉偶联方法基于镍和光氧化还原催化的结合，在环境温度下进行，并使用现成的二氢吡啶作为氨基甲酰基自由基的前体。该方法温和的反应条件使其能够耐受敏感的官能团底物，并允许在生物学相关的杂环中安装酰胺支架。此外，我们安装了带有电子贫乏和空间受阻胺部分的酰胺官能团，而这是用传统的脱水缩合方法难以制备的。
• Homogeneous catalytic aminocarbonylation of nitrogen-containing iodo-heteroaromatics. Synthesis of N-substituted nicotinamide related compounds
  作者：Attila Takács、Balázs Jakab、Andrea Petz、László Kollár

  DOI：10.1016/j.tet.2007.07.017

  日期：2007.10

  Various primary and secondary amines, including amino acid methyl esters, were used as nucleophiles in palladium-catalysed aminocarbonylation of 2-iodopyridine, 3-iodopyridine and iodopyrazine. N-Substituted nicotinamides and 3-pyridyl-glyoxylamides (2-oxo-carboxamide type derivatives) of potential biological importance can be obtained from 3-iodopyridine as a result of simple and double carbon monoxide

  各种伯胺和仲胺，包括氨基酸甲酯，在钯催化的2-碘吡啶，3-碘吡啶和碘吡嗪的氨基羰基化反应中用作亲核试剂。具有潜在生物学重要性的N-取代的烟酰胺和3-吡啶基-乙二酰乙酰胺（2-氧代-羧酰胺型衍生物）可以分别通过简单和两次一氧化碳插入而从3-碘吡啶获得。后面的例子可以通过使用升高的一氧化碳压力以合成上可接受的产率获得。相反，仅通过使用2-碘吡啶和碘吡嗪在整个压力范围内获得N-烷基/芳基-甲酰胺。
• TRIPETIDE BORONIC ACID OR BORONIC ESTER, PREPARATIVE METHOD AND USE THEREOF
  申请人：Li Runtao

  公开号：US20120135921A1

  公开（公告）日：2012-05-31

  The present invention discloses proteasome inhibitors of tripeptide boronic acids or boronic esters represented by Formula (I), preparative method and use thereof. The proteasome inhibitors are therapeutical agents for treating malignant tumor, various nervous system degenerative diseases, muscle cachexia or diabetes, wherein the malignant tumor is leukemia, gastric cancer, hepatocarcinoma or nasopharyngeal carcinoma.

  本发明公开了由式（I）所表示的三肽硼酸或硼酯的蛋白酶抑制剂，其制备方法及用途。这些蛋白酶抑制剂是用于治疗恶性肿瘤、各种神经系统退行性疾病、肌肉消耗症或糖尿病的治疗剂，其中恶性肿瘤是白血病、胃癌、肝癌或鼻咽癌。
• Chemical and Biological Evaluation of Dipeptidyl Boronic Acid Proteasome Inhibitors for Use in Prodrugs and Pro-Soft Drugs Targeting Solid Tumors
  作者：Lawrence J. Milo、Jack H. Lai、Wengen Wu、Yuxin Liu、Hlaing Maw、Youhua Li、Zhiping Jin、Ying Shu、Sarah E. Poplawski、Yong Wu、David G. Sanford、James L. Sudmeier、William W. Bachovchin

  DOI：10.1021/jm200460q

  日期：2011.7.14

  Bortezomib, a dipeptidyl boronic acid and potent inhibitor of the 26S proteasome, is remarkably effective against multiple myeloma (MM) but not against solid tumors. Dose-limiting adverse effects from "on target" inhibition of the proteasome in normal cells and tissues appear to be a key obstacle. Achieving efficacy against solid tumors therefore is likely to require making the inhibitor more selective for tumor tissue over normal tissues. The simplest strategy that might provide such tissue specificity would be to employ a tumor specific protease to release an inhibitor from a larger, noninhibitory structure. However, such release would necessarily generate an inhibitor with a free N-terminal amino group, raising a key question: Can short peptide boronic acids with N-terminal amino groups have the requisite properties to serve as warheads in prodrugs? Here we show that dipeptides of boroLeu, the smallest plausible candidates for the task, can indeed be sufficiently potent, cell-penetrating, cytotoxic, and stable to degradation by cellular peptidases to serve in this capacity.