3-amino-N-benzyl-6-phenylpyrazine-2-carboxamide | 625459-24-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 3-amino-N-benzyl-6-phenylpyrazine-2-carboxamide
• CAS: 625459-24-7
• 化学式: C₁₈H₁₆N₄O
• 分子量: 304.351
• InChiKey: NGTVFGMXCVIGEV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  80.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-氨基-6-溴吡嗪-2-甲酸甲酯 、 苄胺 在 bis-triphenylphosphine-palladium(II) chloride 、 1,1'-双(二苯基膦)二茂铁 、 四丁基溴化铵 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 4.0h， 生成 3-amino-N-benzyl-6-phenylpyrazine-2-carboxamide
  参考文献：
  名称：

  6-Arylpyrazine-2-carboxamides: A New Core for Trypanosoma brucei Inhibitors

  摘要：

  From a whole-organism high throughput screen of approximately 87000 compounds against Trypanosoma brucei brucei, we recently identified eight new unique compounds for the treatment of human African trypanosomiasis. In an effort to understand the structure activity relationships around these compounds, we report for the first time our results on a new class of trypanocides, the pyrazine carboxamides. Attracted by the low molecular weight (270 g.mol(-1)) of our starting hit (9) and its potency (0.49 mu M), the SAR around the core was explored, leading to compounds having an EC50 as low as 25 nM against T. b. brucei and being more than 1500 times less toxic against mammalian L6 and HEK293 cell lines. The most potent compounds in the series were exquisitely selective for T. brucei over a panel of other protozoan parasites, showing an excellent correlation with the human infective parasite Trypanosoma brucei rhodesiense, the most potent compound (65) having an EC50 of 24 nM. The compounds are highly drug-like and are able to penetrate the CNS, their only limitation currently being their rate of microsomal metabolism. To that effect, efforts to identify potential metabolites of selected compounds are also reported.

  DOI：

  10.1021/acs.jmedchem.5b00438

文献信息

• Novel pyrazine compounds as transforming growth factor (TGF) compounds
  申请人：Pfizer Inc

  公开号：US20040180905A1

  公开（公告）日：2004-09-16

  Novel pyrazine compounds, including derivatives thereof, to intermediates for their preparation, to pharmaceutical compositions containing them and to their medicinal use are described. The compounds of the present invention are potent inhibitors of transforming growth factor (“TGF”)-&bgr; signaling pathway. They are useful in the treatment of various TGF-related disease states including, for example, cancer and fibrotic diseases.

  本发明描述了新型吡啶化合物，包括其衍生物，以及用于其制备的中间体，含有它们的药物组合物以及它们的药用。本发明的化合物是转化生长因子（“TGF”）-β信号通路的有效抑制剂。它们在治疗包括癌症和纤维病等各种与TGF相关的疾病状态中非常有用。
• Protein kinase modulators and methods of use
  申请人：Buhr A. Chris

  公开号：US20060211709A1

  公开（公告）日：2006-09-21

  Substituted aryl 1,4-pyrazine derivatives and their use in treating anxiety disorders, depression and stress related disorders are disclosed.

  本发明揭示了替代芳基1,4-吡嗪衍生物及其在治疗焦虑症、抑郁症和与压力相关的疾病中的应用。
• PROTEIN KINASE MODULATORS AND METHODS OF USE
  申请人：Exelixis, Inc.

  公开号：EP1501514A2

  公开（公告）日：2005-02-02
• EP1501514A4
  申请人：——

  公开号：EP1501514A4

  公开（公告）日：2009-08-26
• PYRAZINE COMPOUNDS AS TRANSFORMING GROWTH FACTOR (TGF) INHIBITORS
  申请人：Pfizer Products Inc.

  公开号：EP1606267B1

  公开（公告）日：2008-07-30