吡嗪尿酸 | 57229-37-5

• 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
• 中文名称: 吡嗪尿酸
• 英文名称: (pyrazine-2-carbonyl) glycine
• 英文别名: N-(Pyrazinylcarbonyl)glycine；2-(pyrazine-2-carbonylamino)acetic acid
• CAS: 57229-37-5
• 化学式: C₇H₇N₃O₃
• mdl: MFCD09048392
• 分子量: 181.151
• InChiKey: VEIDKUXSCXOFHB-UHFFFAOYSA-N

物化性质

• 熔点：
  229-230 °C
• 沸点：
  537.1±40.0 °C(Predicted)
• 密度：
  1.422±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.142
• 拓扑面积：
  92.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  吡嗪尿酸 在 一水合肼 、 三氯氧磷 作用下， 以 正丁醇 为溶剂， 反应 7.0h， 生成 N-(1,2-dihydro-3-oxo-3H-pyrazol-4-yl)pyrazine-2-carboxamide
  参考文献：
  名称：

  Kepe, Vladimir; Kozjan, Viktor; Polanc, Slovenko, Heterocycles, 1999, vol. 50, # 1, p. 315 - 322

  摘要：

  DOI：
• 作为产物：
  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

文献信息

• New Pyrazine Conjugates: Synthesis, Computational Studies, and Antiviral Properties against SARS‐CoV‐2
  作者：Israa A. Seliem、Adel S. Girgis、Yassmin Moatasim、Ahmed Kandeil、Ahmed Mostafa、Mohamed A. Ali、Mohamed S. Bekheit、Siva S. Panda

  DOI：10.1002/cmdc.202100476

  日期：2021.11.19

  Antiviral drug development for SARS-CoV-2: The design and microwave-assisted synthesis of pyrazine conjugates are reported. Some of the newly synthesized conjugates show better antiviral activity and selectivity indexes than those of the reference drug. All the lead compounds exhibited low cytotoxicity. Thus, these conjugates could lead to the development of potential drug candidates for SARS-CoV-2.

  SARS-CoV-2 抗病毒药物开发：报告了吡嗪缀合物的设计和微波辅助合成。一些新合成的缀合物表现出比参比药物更好的抗病毒活性和选择性指标。所有先导化合物均表现出较低的细胞毒性。因此，这些缀合物可能导致 SARS-CoV-2 潜在候选药物的开发。
• One-pot synthesis of some 2<i>H</i>-Pyran-2-one derivatives
  作者：Vladimir Kepe、Marijan Kočevar、Slovenko Polanc

  DOI：10.1002/jhet.5570330626

  日期：1996.11

  A one-pot synthesis of various 2H-pyran-2-one derivatives 5–19 starting from methyl ketones 1, N,N-dimethylformamide dimethyl acetal and N-acylglycines 3 in acetic anhydride is described.

  描述了在乙酸酐中从甲基酮1，N，N-二甲基甲酰胺二甲基乙缩醛和N-酰基甘氨酸3开始合成各种2 H-吡喃-2-酮衍生物5-19的方法。
• N-Pyrazinoyl Substituted Amino Acids as Potential Antimycobacterial Agents—the Synthesis and Biological Evaluation of Enantiomers
  作者：Martin Juhás、Lucie Kučerová、Ondřej Horáček、Ondřej Janďourek、Vladimír Kubíček、Klára Konečná、Radim Kučera、Pavel Bárta、Jiří Janoušek、Pavla Paterová、Jiří Kuneš、Martin Doležal、Jan Zitko

  DOI：10.3390/molecules25071518

  日期：——

  tied to the more lipophilic compounds. The most active derivative contained phenylglycine moiety (PC-d/l-Pgl-Me, MIC < 1.95 µg/mL). All active compounds possessed low cytotoxicity and good selectivity towards Mtb. To the best of our knowledge, this is the first study comparing the activities of the d- and l-amino acid derivatives of pyrazinamide as potential antimycobacterial compounds.

  结核病是由结核分枝杆菌（Mtb）引起的传染病，每年导致数百万人死亡。在本文中，我们介绍了新型潜在抗分枝杆菌化合物的合成和生物学评价，该化合物含有一线抗结核药物吡嗪酰胺（PZA）的片段，以及选定氨基酸的甲酯或乙酯。对多种（分枝）细菌菌株（包括 Mtb H37Ra、耻垢分枝杆菌、金黄色分枝杆菌、金黄色葡萄球菌、铜绿假单胞菌）和真菌菌株（包括白色念珠菌和黄曲霉）的抗菌活性进行了评估。重点放在对映体活性的比较上。合成的化合物均未表现出明显的抗真菌活性，且抗菌活性也较低，最佳最低抑菌浓度（MIC）值为31.25 µM。然而，有几种化合物对 Mtb 具有很高的活性。总体而言，含有 L-氨基酸的衍生物具有更高的活性。同样，该活性似乎与亲脂性更强的化合物有关。最活跃的衍生物含有苯基甘氨酸部分（PC-d/l-Pgl-Me，MIC < 1.95 µg/mL）。所有活性化合物均具有低细胞毒性和对 Mtb 的良好
• Bortezomib Congeners Induce Apoptosis of Hepatocellular Carcinoma via CIP2A Inhibition
  作者：Duen-Ren Hou、Ann-Chi Huang、Chung-Wai Shiau、Chun-Yi Wang、Hui-Chuan Yu、Kuen-Feng Chen

  DOI：10.3390/molecules181215398

  日期：——

  CIP2A is an oncoprotein that upregulates p-Akt and promotes cancer cell proliferation and survival. The proteasome inhibitor bortezomib has been shown to reduce CIP2A and lead to cell apoptosis. Here; we modified the functional group of bortezomib to generate a series of novel compounds and conducted a structure–activity relationship (SAR) study. The results showed that compound 1 was able to repress CIP2A expression and cell apoptosis in the same manner as bortezomib, but with less potency in inhibition of proteasome activity. This finding provides a new direction for the design of CIP2A inhibitors.

  CIP2A 是一种上调 p-Akt 并促进癌细胞增殖和存活的肿瘤蛋白。蛋白酶体抑制剂硼替佐米已被证明能减少 CIP2A 并导致细胞凋亡。在此，我们对硼替佐米的官能团进行了修饰，生成了一系列新型化合物，并进行了结构-活性关系（SAR）研究。结果表明，化合物 1 能够以与硼替佐米相同的方式抑制 CIP2A 的表达和细胞凋亡，但对蛋白酶体活性的抑制作用较弱。这一发现为 CIP2A 抑制剂的设计提供了新的方向。
• 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。