2-[4-[2-[[5-[(2-methoxypyridin-4-yl)methyl]-6-oxo-1H-pyrimidin-2-yl]amino]ethylsulfanylmethyl]-1,3-thiazol-2-yl]guanidine | 153901-92-9

• 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: 2-[4-[2-[[5-[(2-methoxypyridin-4-yl)methyl]-6-oxo-1H-pyrimidin-2-yl]amino]ethylsulfanylmethyl]-1,3-thiazol-2-yl]guanidine
• CAS: 153901-92-9
• 化学式: C₁₈H₂₂N₈O₂S₂
• 分子量: 446.557
• InChiKey: NRSZMZGQKZTYDX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  206
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-[4-[2-[[5-[(2-methoxypyridin-4-yl)methyl]-6-oxo-1H-pyrimidin-2-yl]amino]ethylsulfanylmethyl]-1,3-thiazol-2-yl]guanidine 在 盐酸 作用下， 以 乙醇 为溶剂， 以68%的产率得到
  参考文献：
  名称：

  Isocytosine H2-receptor histamine antagonists. IV. The synthesis and biological activity of donetidine (SK&F 93574) and related compounds

  摘要：

  The synthesis and biological activity of some novel 2-amino-4-pyrimidone derivatives is described. Side-chains associated with H-2-antagonist activity am attached through the 2-amino group, whilst a range of 2-hydroxypyridine containing moieties are substituted at the 5-position of the pyrimidone ring. Good H-2-receptor histamine antagonist activity is observed with all the series and the majority of the compounds are selective for the H-2-receptor. High aqueous solubility and iv potency coupled with an extended duration of biological activity in animal models led to compound 16c, 2-[2-(5-dimethylaminomethyl-2-furanylmethyl-thio)ethylamino]-5-(2-hydroxypyrid-4-ylmethyl)-4-pyrimidone (donetidine, SK&F 93574) being selected for clinical investigation as a potential parenterally administered therapeutic agent.

  DOI：

  10.1016/0223-5234(93)90091-r
• 作为产物：
  描述：

  4-氰基-2-甲氧基吡啶 在 palladium on activated charcoal 、 镍 哌啶 、 吡啶 、 盐酸 、 聚合甲醛 、 氢气 、 sodium methylate 、 盐酸氨基脲 、 sodium acetate 、 sodium hydride 作用下， 以 甲醇 、 乙二醇二甲醚 、 乙醇 为溶剂， 反应 62.5h， 生成 2-[4-[2-[[5-[(2-methoxypyridin-4-yl)methyl]-6-oxo-1H-pyrimidin-2-yl]amino]ethylsulfanylmethyl]-1,3-thiazol-2-yl]guanidine
  参考文献：
  名称：

  Isocytosine H2-receptor histamine antagonists. IV. The synthesis and biological activity of donetidine (SK&F 93574) and related compounds

  摘要：

  The synthesis and biological activity of some novel 2-amino-4-pyrimidone derivatives is described. Side-chains associated with H-2-antagonist activity am attached through the 2-amino group, whilst a range of 2-hydroxypyridine containing moieties are substituted at the 5-position of the pyrimidone ring. Good H-2-receptor histamine antagonist activity is observed with all the series and the majority of the compounds are selective for the H-2-receptor. High aqueous solubility and iv potency coupled with an extended duration of biological activity in animal models led to compound 16c, 2-[2-(5-dimethylaminomethyl-2-furanylmethyl-thio)ethylamino]-5-(2-hydroxypyrid-4-ylmethyl)-4-pyrimidone (donetidine, SK&F 93574) being selected for clinical investigation as a potential parenterally administered therapeutic agent.

  DOI：

  10.1016/0223-5234(93)90091-r

文献信息

• Pyrimidone derivatives, processes for their preparation and pharmaceutical compositions containing them
  申请人：SMITH KLINE & FRENCH LABORATORIES LIMITED

  公开号：EP0015138B1

  公开（公告）日：1983-03-16
• US4521418A
  申请人：——

  公开号：US4521418A

  公开（公告）日：1985-06-04
• Isocytosine H2-receptor histamine antagonists. IV. The synthesis and biological activity of donetidine (SK&F 93574) and related compounds
  作者：TH Brown、RC Blakemore、GJ Durant、CR Ganellin、ME Parsons、AC Rasmussen、DA Rawlings

  DOI：10.1016/0223-5234(93)90091-r

  日期：1993.1

  The synthesis and biological activity of some novel 2-amino-4-pyrimidone derivatives is described. Side-chains associated with H-2-antagonist activity am attached through the 2-amino group, whilst a range of 2-hydroxypyridine containing moieties are substituted at the 5-position of the pyrimidone ring. Good H-2-receptor histamine antagonist activity is observed with all the series and the majority of the compounds are selective for the H-2-receptor. High aqueous solubility and iv potency coupled with an extended duration of biological activity in animal models led to compound 16c, 2-[2-(5-dimethylaminomethyl-2-furanylmethyl-thio)ethylamino]-5-(2-hydroxypyrid-4-ylmethyl)-4-pyrimidone (donetidine, SK&F 93574) being selected for clinical investigation as a potential parenterally administered therapeutic agent.