methyl N-(pyrazinecarbonyl)glycinate | 117904-01-5

• 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: methyl N-(pyrazinecarbonyl)glycinate
• 英文别名: (N-(methoxycarbonylmethyl)-carboxamido)-pyrazine；Methyl 2-(pyrazine-2-carbonylamino)acetate
• CAS: 117904-01-5
• 化学式: C₈H₉N₃O₃
• mdl: MFCD12144119
• 分子量: 195.178
• InChiKey: RGZXRTNDGXRBOA-UHFFFAOYSA-N

物化性质

• 沸点：
  429.9±35.0 °C(Predicted)
• 密度：
  1.277±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 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：

  methyl N-(pyrazinecarbonyl)glycinate 在 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 3.0h， 生成 吡嗪尿酸
  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：

  吡嗪-2-羧酸甲酯 在 盐酸 、 sodium methylate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 17.5h， 生成 methyl N-(pyrazinecarbonyl)glycinate
  参考文献：
  名称：

  某些N-（吡嗪羰基）氨基酸和肽的合成

  摘要：

  已经合成了具有吡嗪羰基或3-氨基吡嗪羰基的一些氨基酸的衍生物，并制备了一些肽。在3-氨基吡嗪羰基衍生物的情况下，可以制备缩合的嘧啶，即4（3H）-哌啶酮衍生物。

  DOI：

  10.1002/recl.19881070503

文献信息

• 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。
• Kepe, Vladimir; Kozjan, Viktor; Polanc, Slovenko, Heterocycles, 1999, vol. 50, # 1, p. 315 - 322
  作者：Kepe, Vladimir、Kozjan, Viktor、Polanc, Slovenko、Kocevar, Marijan

  DOI：——

  日期：——
• KOCEVAR, MARIJAN;POLANC, SLOVENKO;VERCEK, BOJAN;TISLER, MIHA, REC. TRAV. CHIM. PAYS-BAS, 107,(1988) N 5, 366-369
  作者：KOCEVAR, MARIJAN、POLANC, SLOVENKO、VERCEK, BOJAN、TISLER, MIHA

  DOI：——

  日期：——
• 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.
• Syntheses of some N-(pyrazinecarbonyl) amino acids and peptides
  作者：Marijan Kočvar、Slovenko Polanc、Bojan Verček、Miha Tišler

  DOI：10.1002/recl.19881070503

  日期：——

  Derivatives of some amino acids, having a pyrazinecarbonyl or 3-aminopyrazinecarbonyl radical, have been synthesized and some peptides prepared. In the case of the 3-aminopyrazinecarbonyl derivatives, condensed pyrimidines, i.e. 4(3H)-pteridinone derivatives, could be prepared.

  已经合成了具有吡嗪羰基或3-氨基吡嗪羰基的一些氨基酸的衍生物，并制备了一些肽。在3-氨基吡嗪羰基衍生物的情况下，可以制备缩合的嘧啶，即4（3H）-哌啶酮衍生物。