methyl N-cyano-N'-[2-[[3-(4-methylphenyl)-6-oxopyridazin-1-yl]methylsulfanyl]ethyl]carbamimidothioate | 79460-55-2

• 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: methyl N-cyano-N'-[2-[[3-(4-methylphenyl)-6-oxopyridazin-1-yl]methylsulfanyl]ethyl]carbamimidothioate
• CAS: 79460-55-2
• 化学式: C₁₇H₁₉N₅OS₂
• 分子量: 373.503
• InChiKey: GJKXUGCLNGDDBG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  131
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl N-cyano-N'-[2-[[3-(4-methylphenyl)-6-oxopyridazin-1-yl]methylsulfanyl]ethyl]carbamimidothioate 、 甲胺 以 甲醇 为溶剂， 反应 7.0h， 以78%的产率得到1-Cyano-2-methyl-3-[2-[[3-(4-methylphenyl)-6-oxopyridazin-1-yl]methylsulfanyl]ethyl]guanidine
  参考文献：
  名称：

  Pyridazinones. 3. Synthesis, antisecretory, and antiulcer activities of 2-cyanoguanidine derivatives

  摘要：

  3(2H)-Pyridazinone derivatives having a 2-cyanoguanidine moiety, as well as a sulfur or an oxygen atom in the alkylene side chain, were synthesized and evaluated for gastric antisecretory and antiulcer activities. The key intermediates, free amines having a thioether linkage, were synthesized by the reaction of 2-(omega-chloroalkyl) derivatives with cysteamine, while other intermediates having an ether linkage were synthesized from 2-(omega-chloroalkyl)oxymethyl derivatives. These free amines were converted via the 3-cyano-2-methyl-1-isothiourea derivatives into the desired 2-cyano-3-substituted-1-guanidine derivatives. All compounds synthesized were evaluated for gastric antisecretory activity in the pylorus-ligated rat by the method of Shay, and selected compounds were evaluated in the stress-induced ulcer test in rat. Structure-activity relationships are discussed. The molecular features for the best activities are a phenyl group in the C-6 position of the 3(2H)-pyridazinone ring, a four-atom chain length between the 3(2H)-pyridazinone ring and the 2-cyanoguanidine moiety, and a thioether rather than an ether linkage. Among them, compound 14, 2-[[[2-(2-cyano-3-methyl-1-guanidino)ethyl]thio]methyl]-6-phenyl-3 (2H)-pyridazinone, had the most potent antisecretory and antiulcer activities. These compounds are neither histamine H2 receptor inhibitors nor anticholinergic agents.

  DOI：

  10.1021/jm00362a011
• 作为产物：
  描述：

  2-(2-aminoethylsulfanylmethyl)-6-(4-methylphenyl)pyridazin-3-one 、 N-氰亚胺基-S,S-二硫代碳酸二甲酯 以 乙醇 为溶剂， 以49%的产率得到methyl N-cyano-N'-[2-[[3-(4-methylphenyl)-6-oxopyridazin-1-yl]methylsulfanyl]ethyl]carbamimidothioate
  参考文献：
  名称：

  Pyridazinones. 3. Synthesis, antisecretory, and antiulcer activities of 2-cyanoguanidine derivatives

  摘要：

  3(2H)-Pyridazinone derivatives having a 2-cyanoguanidine moiety, as well as a sulfur or an oxygen atom in the alkylene side chain, were synthesized and evaluated for gastric antisecretory and antiulcer activities. The key intermediates, free amines having a thioether linkage, were synthesized by the reaction of 2-(omega-chloroalkyl) derivatives with cysteamine, while other intermediates having an ether linkage were synthesized from 2-(omega-chloroalkyl)oxymethyl derivatives. These free amines were converted via the 3-cyano-2-methyl-1-isothiourea derivatives into the desired 2-cyano-3-substituted-1-guanidine derivatives. All compounds synthesized were evaluated for gastric antisecretory activity in the pylorus-ligated rat by the method of Shay, and selected compounds were evaluated in the stress-induced ulcer test in rat. Structure-activity relationships are discussed. The molecular features for the best activities are a phenyl group in the C-6 position of the 3(2H)-pyridazinone ring, a four-atom chain length between the 3(2H)-pyridazinone ring and the 2-cyanoguanidine moiety, and a thioether rather than an ether linkage. Among them, compound 14, 2-[[[2-(2-cyano-3-methyl-1-guanidino)ethyl]thio]methyl]-6-phenyl-3 (2H)-pyridazinone, had the most potent antisecretory and antiulcer activities. These compounds are neither histamine H2 receptor inhibitors nor anticholinergic agents.

  DOI：

  10.1021/jm00362a011

文献信息

• YAMADA, TOSHIHIRO;SHIMAMURA, HIROSHI;TSUKAMOTO, YOSHITSUGU;YAMAGUCHI, AZU+, J. MED. CHEM., 1983, 26, N 8, 1144-1149
  作者：YAMADA, TOSHIHIRO、SHIMAMURA, HIROSHI、TSUKAMOTO, YOSHITSUGU、YAMAGUCHI, AZU+

  DOI：——

  日期：——
• Derivatives of 2-substituted-6-phenyl-3(2H)pyridazinone, their production and pharmaceutical compositions containing them
  申请人：MORISHITA PHARMACEUTICAL CO. LTD.

  公开号：EP0030835B1

  公开（公告）日：1983-05-11