N-(pyrazinecarbonyl)-L-alanine

• 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-(pyrazinecarbonyl)-L-alanine
• 英文别名: (pyrazine-2-carbonyl)-l-alanine；PC-L-Ala；(2S)-2-(pyrazine-2-carbonylamino)propanoic acid
• 化学式: C₈H₉N₃O₃
• 分子量: 195.178
• InChiKey: XSLUOYXJSZVRTN-YFKPBYRVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 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：

  N-(pyrazinecarbonyl)-L-alanine 、 (R)-boroLeu-(+)-pinanediol 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成
  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 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 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 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

文献信息

• 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
• 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。
• 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。
• 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.