6-(4-Hydroxy-1-piperidinyl)-N-(1H-5-tetrazolyl-)pyrazine-2-carboxamide | 111374-25-5

• 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: 6-(4-Hydroxy-1-piperidinyl)-N-(1H-5-tetrazolyl-)pyrazine-2-carboxamide
• 英文别名: 6-(4-hydroxypiperidin-1-yl)-N-(2H-tetrazol-5-yl)pyrazine-2-carboxamide
• CAS: 111374-25-5
• 化学式: C₁₁H₁₄N₈O₂
• 分子量: 290.285
• InChiKey: IXZRYCDCZTYORS-UHFFFAOYSA-N

物化性质

• 密度：
  1.594±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  133
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  5-氨基四氮唑 生成 6-(4-Hydroxy-1-piperidinyl)-N-(1H-5-tetrazolyl-)pyrazine-2-carboxamide
  参考文献：
  名称：

  ITOH, YASUO;KATO, HIDEO;KOSHINAKA, EIICHI;OGAWA, NOBUO;MITANI, KAZUYA

  摘要：

  DOI：

文献信息

• Pyrazine-2-carboxamide derivatives useful in treating allergic disease
  申请人：Hokuriku Pharmaceutical Co., Ltd.

  公开号：US04792547A1

  公开（公告）日：1988-12-20

  Novel pyrazine derivatives useful for treatment of bronchial asthma, allergic gastorenteric trouble, hay fever urticaria, allertic rhinitis, and allergic conjunctivitis, and pharmaceutical compositions thereof, are disclosed. The compounds have the formula I as follows: ##STR1## wherein R represents hydrogen or ##STR2## wherein R.sub.1 and R.sub.2 may be the same or different and each independently represents hydrogen, straight or branched-chain lower-alkyl, or cycloalkyl having three to six carbon atoms inclusive, phenyl which may be substituted with halogen, lower-alkyl, or lower-alkoxy, or wherein R.sub.1 and R.sub.2 together represent alkylene of four to six carbon atoms, inclusive, optionally interrupted by one or two nitrogen atoms or one oxygen atom and said ring being optionally substituted by straight or branched-chain lower-alkyl having one to six carbon atoms inclusive, hydroxy, or phenyl, and pharmaceutically-acceptable salts thereof.

  本发明揭示了用于治疗支气管哮喘、过敏性胃肠障碍、花粉热性荨麻疹、过敏性鼻炎和过敏性结膜炎的新型吡嗪衍生物及其制药组合物。该化合物的化学式如下：##STR1## 其中R表示氢或##STR2## 其中R.sub.1和R.sub.2可以相同也可以不同，并且分别独立地表示氢、直链或支链低碳基、或含有三至六个碳原子的环烷基，苯基可以被卤素、低碳基或低碳氧基取代，或者R.sub.1和R.sub.2共同表示四到六个碳原子的烷基，可以被一个或两个氮原子或一个氧原子中断，该环可以被直链或支链低碳基（包括1-6个碳原子）、羟基或苯基取代，以及其药学上可接受的盐。
• Studies on antiallergic agents. II. Quantitative structure-activity relationships of novel 6-substituted N-(1H-tetrazol-5-yl)-2-pyrazinecarboxamides.
  作者：Eiichi MAKINO、Kazuya MITANI、Nobuhiko IWASAKI、Hideo KATO、Yasuo ITO、Hiroshi AZUMA、Toshio FUJITA

  DOI：10.1248/cpb.38.1250

  日期：——

  The effects of structural modifications of 6-substituted N-(1H-tetrazol-5-yl)-2-pyrazinecarboxamides on their anti-allergic activity was analyzed quantitatively by means of the Hansch-Fujita method. The activity of these compounds was correlated with hydrophobic (π) and steric (molecular refractivity and STERIMOL B1) effects of the 6-substituent on the pyrazine ring. The 6-substituents with a length greater than n-propylamino possess an extra effect enhancing the activity. Moreover, the activity increased progressively from 6-non-amino via alkylamino- to dialkylamino-substituted compounds, other factors being equal. This could be attributable to an electronic effect of substituents. Electron-donating small and yet symmetric substituents with high hydrophobicity longer than n-propylamino seemed to be favorable to the activity. By compromising these contradictory requirements, small dialkylamino (including cyclic amino) groups were decided to be the most favorable substituents. This analysis was in agreement with the observation that the most effective compounds were the 6-dimethylamino (I-27) and 6-(1-pyrrolidinyl) (I-34) derivatives.

  通过汉斯-藤田法对6-取代N-(1H-四唑-5-基)-2-吡嗪甲酰胺的结构修饰对其抗过敏活性的影响进行了定量分析。这些化合物的活性与吡嗪环上6-取代基的疏水（π）和空间（分子折射率和STERIMOL B1）效应相关。长度大于正丙基氨基的6-取代基具有增强活性的额外效应。此外，在其他因素相同的情况下，活性从6-非氨基到烷基氨基和二烷基氨基取代的化合物逐渐增加。这可能是由于取代基的电子效应。具有高疏水性且长度大于正丙基氨基的供电子小而对称取代基似乎有利于活性。通过权衡这些矛盾的要求，决定小二烷基氨基（包括环状氨基）基团是最有利的取代基。这一分析结果与观察结果一致，即最有效的化合物是6-二甲基氨基（I-27）和6-(1-吡咯烷基)（I-34）衍生物。
• Pyrazine derivative, a process for preparation thereof and pharmaceutical composition therefrom
  申请人：Hokuriku Pharmaceutical Co.,Ltd

  公开号：EP0227026A1

  公开（公告）日：1987-07-01

  Novel pyrazine derivatives useful for treatment of bronchial asthma, allergic gastroenteric trouble, hay fever urticaria, allergic rhinitis, allergic conjunctivitis are disclosed.

  公开了可用于治疗支气管哮喘、过敏性肠胃病、花粉热荨麻疹、过敏性鼻炎和过敏性结膜炎的新型吡嗪衍生物。
• US4792547A
  申请人：——

  公开号：US4792547A

  公开（公告）日：1988-12-20