N-tert-butyl-N'-(4-1H-imidazol-4-ylphenyl)formamidine | 83184-14-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-tert-butyl-N'-(4-1H-imidazol-4-ylphenyl)formamidine
• 英文别名: N-(tert-butyl)-N'-[4-(1H-imidazol-4-yl)phenyl]imidoformamide；N'-tert-butyl-N-[4-(1H-imidazol-5-yl)phenyl]methanimidamide
• CAS: 83184-14-9
• 化学式: C₁₄H₁₈N₄
• 分子量: 242.324
• InChiKey: KUEHILWIADUSSA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  53.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  4-(1H-咪唑-4-基)苯胺盐酸盐 、 ethyl N-tert-butylformimidate tetrafluoroborate 以 乙醇 、 二氯甲烷 为溶剂， 反应 8.0h， 生成 N-tert-butyl-N'-(4-1H-imidazol-4-ylphenyl)formamidine
  参考文献：
  名称：

  (Imidazolylphenyl)formamidines. A structurally novel class of potent histamine H2 receptor antagonists

  摘要：

  Structure-activity considerations of N alpha-guanylhistamine, the first compound found with detectable H2-antagonist activity, led to the synthesis of a series of conformationally rigid guanylhistamine analogues, namely, (imidazolylphenyl)guanidines, imidazolylbenzamidines, and (imidazolylphenyl)formamidines. It was found that in the guanidine and benzamidine classes, the meta-substituted derivatives (3, 4, 7, and 8) possessed H2-antagonist activity, whereas in the class of formamidines, only the para-substituted derivative 10 was found active. A subsequent increase in the size of the substituent at the formamidino group of 10 led to compounds (15-20) of high H2-antagonist affinity, which was related to the gastric antisecretory effect. Members of this structurally novel class of H2 antagonists were 20- to 50-fold more potent than cimetidine both "in vitro" and "in vivo". Structure-activity relationships are discussed in terms of ionization properties, partitioning behavior, conformational aspects of the selected compound 17, and of possible modes of interaction with the histamine H2 receptor. It was found that the formamidine moiety was an important structural feature and that H2-antagonist activity requires correct steric and electronic properties. Compound 17 (DA 4577), owing to its pharmacological profile and demonstrated safety in animals, was selected to be clinically investigated.

  DOI：

  10.1021/jm00369a025

文献信息

• New imidazolylphenyl amidines, processes for their preparation and their pharmaceutical use, and intermediates of preparation
  申请人：ISTITUTO DE ANGELI S.p.A.

  公开号：EP0053407A2

  公开（公告）日：1982-06-09

  The object of the present invention are new pharmacologically active substituted imidazolylphenyl amidines as H2 receptor blocking agents, which inhibit gastric acid secretion and which are useful antiulcer agents of the following formula in which R, R, and R3, which may be the same or different, represent a hydrogen atom or a lower alkyl group, and R2 represents a linear or branched alkyl, alkenyl or alkynyl group, a cyano group, a hydroxyl group, a substituted or unsubstituted cycloalkyl or cycloaliphatic alkyl group, a bicyclic group, an aralkyl or aryl group (optionally substituted by halogen, a methyl, methoxy or methylenedioxy group) or a substituted or unsubstituted heterocyclicalkyl or heterocyclic group which may also contain a further hetero atom; and non-toxic acid addition salts thereof. The processes for the preparation of the compounds of formula and their intermediates as well as pharmaceutical compositions containing them are also object of this invention.

  本发明的目的是作为 H2 受体阻断剂的新的药理活性取代咪唑基苯基酰胺，它可抑制胃酸分泌，是下式中有用的抗溃疡剂 其中 R、R 和 R3（可以相同或不同）代表氢原子或低级烷基，R2 代表直链或支链烷基、烯基或炔基、氰基、羟基、取代或未取代的环烷基或环脂族烷基、双环基、芳烷基或芳基（可选择被卤素、甲基、甲氧基或亚甲二氧基基团取代）或取代或未取代的杂环烷基或杂环基，其中还可含有另一个杂原子；及其无毒酸加成盐。制备式化合物及其中间体以及含有它们的药物组合物的工艺也是本发明的目的。
• US4386099A
  申请人：——

  公开号：US4386099A

  公开（公告）日：1983-05-31
• US4465841A
  申请人：——

  公开号：US4465841A

  公开（公告）日：1984-08-14