3-氨基-n-甲基吡嗪-2-羧酰胺 | 36204-76-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 3-氨基-n-甲基吡嗪-2-羧酰胺
• 英文名称: 3-Aminopyrazin-2-(N-methyl)carboxamid
• 英文别名: 3-amino-pyrazine-2-carboxylic acid methylamide；3-Amino-pyrazin-2-carbonsaeure-methylamid；3-amino-N-methyl-2-pyrazinecarboxamide；3-amino-N-methylpyrazine-2-carboxamide
• CAS: 36204-76-9
• 化学式: C₆H₈N₄O
• mdl: MFCD09953009
• 分子量: 152.156
• InChiKey: LOORHJQGRKWHBI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.166
• 拓扑面积：
  80.9
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2934999090
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302

反应信息

• 作为反应物：
  描述：

  3-氨基-n-甲基吡嗪-2-羧酰胺 在 劳森试剂 、 六甲基磷酰三胺 作用下， 以15%的产率得到3-amino-N-methylpyrazine-2-carbothioamide
  参考文献：
  名称：

  Synthesis and Pharmacological Activity of Triazole Derivatives Inhibiting Eosinophilia

  摘要：

  In order to develop novel antiasthmatic agents based on a new mechanism of action, a series of 3-substituted 5-amino-1-[(methylamino)(thiocarbonyl)]-1H-1,2,4-triazole derivatives were synthesized and evaluated in a model in which eosinophilia was induced in the ah-way through intravenous (iv) injection of Sephadex particles on days 0, 2, and 5. After screening of several hundred derivatives, we finally identified the highly potent eosinophilia inhibitor 5-amino-3-(4-chlorophenyl)-1-[(methylamino)(thiocarbonyl)]-1H-triazole (23c, GCC-AP0341), which had ID50 values of 0.3 and 0.07 mg/kg when administered orally (os) and intraperitoneally tip), respectively. This compound showed complete inhibition of the hypersensitivity induced by ascaris inhalation at an ip dose of 1 mg/kg as well as low toxicity, with an LD(50) value of > 2.0 g/kg in mice. Extensive study of its mechanism of action revealed that 23c inhibited eosinophil survival induced by interleukin-5 (IL-5), but had little or no effect on leukotriene D-4 (LTD(4)) or platelet-activating factor (PAF)-induced responses. Taken together, these results suggest 23e as a novel candidate for the treatment of chronic asthma. Further studies are now underway.

  DOI：

  10.1021/jm9507993
• 作为产物：
  描述：

  3-氨基吡嗪-2-羧酸 、 甲胺 在 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 生成 3-氨基-n-甲基吡嗪-2-羧酰胺
  参考文献：
  名称：

  Synthesis and Pharmacological Activity of Triazole Derivatives Inhibiting Eosinophilia

  摘要：

  In order to develop novel antiasthmatic agents based on a new mechanism of action, a series of 3-substituted 5-amino-1-[(methylamino)(thiocarbonyl)]-1H-1,2,4-triazole derivatives were synthesized and evaluated in a model in which eosinophilia was induced in the ah-way through intravenous (iv) injection of Sephadex particles on days 0, 2, and 5. After screening of several hundred derivatives, we finally identified the highly potent eosinophilia inhibitor 5-amino-3-(4-chlorophenyl)-1-[(methylamino)(thiocarbonyl)]-1H-triazole (23c, GCC-AP0341), which had ID50 values of 0.3 and 0.07 mg/kg when administered orally (os) and intraperitoneally tip), respectively. This compound showed complete inhibition of the hypersensitivity induced by ascaris inhalation at an ip dose of 1 mg/kg as well as low toxicity, with an LD(50) value of > 2.0 g/kg in mice. Extensive study of its mechanism of action revealed that 23c inhibited eosinophil survival induced by interleukin-5 (IL-5), but had little or no effect on leukotriene D-4 (LTD(4)) or platelet-activating factor (PAF)-induced responses. Taken together, these results suggest 23e as a novel candidate for the treatment of chronic asthma. Further studies are now underway.

  DOI：

  10.1021/jm9507993

文献信息

• 4(3H)-pteridinones, preparation processes and drugs containing them
  申请人：Lipha, Lyonnaise Industrielle Pharmaceutique

  公开号：US05167949A1

  公开（公告）日：1992-12-01

  The present invention relates to 4(3H)-pteridinones represented by the formula: ##STR1## in which X is an oxygen atom or a sulphur atom, Y is a hydrogen atom, a lower alkyl radical, especially a methyl radical, at the 6-position or a hydroxyl group at the 7-position, R.sub.1 is a hydrogen atom, a lower alkyl radical, a substituted or unsubstituted phenyl radical, a benzyl radical, a methoxymethyl group, an acetyl group, a 2-acetoxyethyl group or a 2,2,2-trifluoroethyl group and R.sub.2 is a hydrogen atom or a lower alkyl radical, especially a methyl radical. Application of these compounds as anti-allergic drugs.

  本发明涉及由以下公式表示的4（3H）-喜树碱酮：##STR1## 其中X是氧原子或硫原子，Y是氢原子，较低的烷基基团，特别是甲基基团，在6位或7位处的羟基基团，R.sub.1是氢原子，较低的烷基基团，取代或未取代的苯基基团，苄基基团，甲氧基甲基基团，乙酰基基团，2-乙酰氧乙基基团或2,2,2-三氟乙基基团，R.sub.2是氢原子或较低的烷基基团，特别是甲基基团。这些化合物作为抗过敏药物的应用。
• 4(3H)-pteridinone compounds
  申请人：Lipha, Lyonnaise Industrille Pharmaceutique

  公开号：US05270465A1

  公开（公告）日：1993-12-14

  The present invention relates to 4(3H)-pteridinones represented by the formula: ##STR1## in which X is an oxygen atom or a sulphur atom, Y is a hydrogen atom, a lower alkyl radical, especially a methyl radical, at the 6-position or a hydroxyl group at the 7-position, R.sub.1 is a hydrogen atom, a lower alkyl radical, a substituted or unsubstituted phenyl radical, a benzyl radical, a methoxymethyl group, an acetyl group, a 2-acetoxyethyl group or a 2,2,2-trifluoroethyl group and R.sub.2 is a hydrogen atom or a lower alkyl radical, especially a methyl radical. Application of these compounds as anti-allergic drugs.

  本发明涉及由以下式表示的4（3H）-喹嗪酮：##STR1## 其中，X是氧原子或硫原子，Y是氢原子，低碳基，特别是甲基基团，在6位或7位处是羟基基团，R1是氢原子，低碳基，取代或未取代的苯基基团，苄基基团，甲氧基甲基基团，乙酰基基团，2-乙酰氧乙基基团或2,2,2-三氟乙基基团，R2是氢原子或低碳基，特别是甲基基团。这些化合物的应用作为抗过敏药物。
• INHIBITORS OF FOCAL ADHESION KINASE
  申请人：Liang Congxin

  公开号：US20110046121A1

  公开（公告）日：2011-02-24

  The invention provides inhibitors of focal adhesion kinase, an enzyme involved in the attachment of the cytoskeleton of a cell to an extracellular matrix, which has been implicated in processes such as cell migration, cell proliferation, and cell survival. The inhibitors are derivatives of a 5-substituted 2,4-diaminopyridine wherein the substituents are as defined herein. The invention also provides a method of using the inhibitors in treatment of cancer, and methods of preparation of the inhibitors by use of coupling reactions.

  该发明提供了聚焦粘附激酶的抑制剂，该酶参与细胞的细胞骨架与细胞外基质的附着，已被证实与细胞迁移、细胞增殖和细胞存活等过程有关。这些抑制剂是5-取代的2,4-二氨基吡啶的衍生物，其中取代基如本文所定义。该发明还提供了使用这些抑制剂治疗癌症的方法，以及通过使用偶联反应制备这些抑制剂的方法。
• Inhibitors of focal adhesion kinase
  申请人：Liang Congxin

  公开号：US08501763B2

  公开（公告）日：2013-08-06

  The invention provides inhibitors of focal adhesion kinase, an enzyme involved in the attachment of the cytoskeleton of a cell to an extracellular matrix, which has been implicated in processes such as cell migration, cell proliferation, and cell survival. The inhibitors are derivatives of a 5-substituted 2,4-diaminopyridine wherein the substituents are as defined herein. The invention also provides a method of using the inhibitors in treatment of cancer, and methods of preparation of the inhibitors by use of coupling reactions.

  本发明提供了针对聚焦粘附激酶（一种参与细胞细胞骨架与细胞外基质附着的酶）的抑制剂，该酶被认为参与了细胞迁移、细胞增殖和细胞存活等过程。这些抑制剂是5-取代-2,4-二氨基吡啶的衍生物，其中取代基如本文所定义。本发明还提供了一种使用这些抑制剂治疗癌症的方法，以及通过使用偶联反应制备这些抑制剂的方法。
• Adenosine-Mimicking Derivatives of 3-Aminopyrazine-2-Carboxamide: Towards Inhibitors of Prolyl-tRNA Synthetase with Antimycobacterial Activity
  作者：Vinod Sukanth Kumar Pallabothula、Marek Kerda、Martin Juhás、Ondřej Janďourek、Klára Konečná、Pavel Bárta、Pavla Paterová、Jan Zitko

  DOI：10.3390/biom12111561

  日期：——

  Multidrug-resistant tuberculosis (MDR-TB) poses a significant threat to mankind and as such earned its place on the WHO list of priority pathogens. New antimycobacterials with a mechanism of action different to currently used agents are highly required. This study presents the design, synthesis, and biological evaluation of 3-acylaminopyrazine-2-carboxamides derived from a previously reported inhibitor of human prolyl-tRNA synthetase. Compounds were evaluated in vitro against various strains of mycobacteria, pathogenic bacteria, and fungi of clinical significance. In general, high activity against mycobacteria was noted, while the antibacterial and antifungal activity was minimal. The most active compounds were 4’-substituted 3-(benzamido)pyrazine-2-carboxamides, exerting MIC (Minimum Inhibitory Concentration) from 1.95 to 31.25 µg/mL. Detailed structure–activity relationships were established and rationalized in silico with regard to mycobacterial ProRS as a probable target. The active compounds preserved their activity even against multidrug-resistant strains of Mycobacterium tuberculosis. At the same time, they were non-cytotoxic against HepG2 human hepatocellular carcinoma cells. This project is the first step in the successful repurposing of inhibitors of human ProRS to inhibitors of mycobacterial ProRS with antimycobacterial activity.

  耐多药结核病（MDR-TB）对人类构成重大威胁，因此被列入世界卫生组织的优先病原体名单。我们亟需作用机制不同于现有药物的新型抗霉菌药物。本研究介绍了 3-酰基氨基吡嗪-2-羧酰胺的设计、合成和生物学评价，这些化合物来自以前报道的一种人类脯氨酰-tRNA 合成酶抑制剂。研究人员对化合物进行了体外评估，以检测其对各种分枝杆菌、致病菌和具有临床意义的真菌的活性。总的来说，这些化合物对分枝杆菌具有很高的活性，而抗菌和抗真菌活性则微乎其微。活性最强的化合物是 4'-取代的 3-（苯甲酰胺基）吡嗪-2-甲酰胺类化合物，其最低抑菌浓度（MIC）从 1.95 微克/毫升到 31.25 微克/毫升不等。以分枝杆菌 ProRS 为可能的靶标，建立了详细的结构-活性关系，并在硅学中加以合理化。这些活性化合物即使对结核分枝杆菌的耐多药菌株也能保持活性。同时，它们对 HepG2 人类肝癌细胞无毒性。该项目是将人类 ProRS 抑制剂成功转化为具有抗分枝杆菌活性的分枝杆菌 ProRS 抑制剂的第一步。