2-<<(2-aminoethyl)oxy>methyl>-6-phenyl-3(2H)-pyridazinone | 79460-67-6

• 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-<<(2-aminoethyl)oxy>methyl>-6-phenyl-3(2H)-pyridazinone
• 英文别名: 2-(2-Aminoethoxymethyl)-6-phenylpyridazin-3-one
• CAS: 79460-67-6
• 化学式: C₁₃H₁₅N₃O₂
• 分子量: 245.281
• InChiKey: LKXZODOBTHKFCY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-<<(2-aminoethyl)oxy>methyl>-6-phenyl-3(2H)-pyridazinone 以 甲醇 、 乙醇 为溶剂， 反应 7.0h， 生成 2-<<<2-(2-cyano-2-methyl-1-guanidino)ethyl>oxy>methyl>-6-phenyl-3(2H)-pyridazinone
  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：

  6-苯基-3-哒嗪酮 在 盐酸 、 ammonium hydroxide 作用下， 以 甲醇 为溶剂， 反应 48.0h， 生成 2-<<(2-aminoethyl)oxy>methyl>-6-phenyl-3(2H)-pyridazinone
  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

• 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：EP0030835A1

  公开（公告）日：1981-06-24

  Although known 6-phenyl-3(2H)-pyridazinone derivatives possess a strong anti-peptic ulcer activity, they do not all exhibit activity over long periods of time and can produce unfavourable side effects. These difficulties are now overcome by derivatives represented by the formula (I): wherein R', R2 and R3 independently represent a hydrogen atom, a halogen atom, a lower alkyl group or a lower alkoxy group; R' and R' independently represent a hydrogen atom or an alkyl group; m represents an integer of 1 to 3; n represents 0 or an integer of from 1 to 3; Z represents -CH2-, -0- or -S-; X represents -S-R6 or -N"H-R', wherein R6 represents a lower alkyl group and R' represents a hydrogen atom, a lower alkyl or a propargyl group, and the carbon atoms at positions 4 and 5 of the heterocyclic ring of the formula (I), to which R' and R' are bonded respectively, are joined by either a single or a double carbon-carbon bond; and acid addition salts thereof; with the proviso that where Z is -0- or -S-, the carbon atoms at positions 4 and 5 joined by a double bond and n represents an integer of 1 to 3. These compounds have therapeutical activity against peptic ulcers.

  虽然已知的 6-苯基-3(2H)-哒嗪酮衍生物具有很强的抗消化性溃疡活性，但它们并不都能长期保持活性，而且会产生不利的副作用。现在，由式（I）表示的衍生物克服了这些困难： 其中 R'、R2 和 R3 分别代表氢原子、卤素原子、低级烷基或低级烷氧基；R'和 R'分别代表氢原子或烷基；m 代表 1 至 3 的整数；n 代表 0 或 1 至 3 的整数；Z 代表 -CH2-、-0- 或 -S-；X代表-S-R6或-N "H-R'，其中R6代表低级烷基，R'代表氢原子、低级烷基或丙炔基，且R'和R'分别键合的式(I)杂环第4位和第5位的碳原子通过单碳碳键或双碳碳键连接；及其酸加成盐；但其中 Z 为-0-或-S-时，第 4 位和第 5 位的碳原子以双键连接，n 为 1 至 3 的整数。这些化合物对消化性溃疡具有治疗活性。
• 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：——
• YAMADA, YASUXIRO;TSUKAMOTO, DZEHNDZI;OMOKU, MASAXIKO
  作者：YAMADA, YASUXIRO、TSUKAMOTO, DZEHNDZI、OMOKU, MASAXIKO

  DOI：——

  日期：——
• Pyridazinones. 3. Synthesis, antisecretory, and antiulcer activities of 2-cyanoguanidine derivatives
  作者：Toshihiro Yamada、Hiroshi Shimamura、Yoshitsugu Tsukamoto、Azuma Yamaguchi、Masahiko Ohki

  DOI：10.1021/jm00362a011

  日期：1983.8

  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.