N-cyano-N'-[4-(imidazol-4-yl)-phenyl]-formamidine | 83184-32-1

• 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-cyano-N'-[4-(imidazol-4-yl)-phenyl]-formamidine
• 英文别名: N-cyano-N'-[4-(1H-imidazol-5-yl)phenyl]methanimidamide
• CAS: 83184-32-1
• 化学式: C₁₁H₉N₅
• 分子量: 211.226
• InChiKey: AEQUIERXHBACLX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  76.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-cyano-N'-[4-(imidazol-4-yl)-phenyl]-formamidine 在 ammonium hydroxide 作用下， 生成 N'-[4-(1H-imidazol-5-yl)phenyl]methanimidamide
  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
• 作为产物：
  描述：

  4-(1H-咪唑-4-基)苯胺盐酸盐 、 N-氰基甲亚胺乙酯 以 乙醇 为溶剂， 以88%的产率得到N-cyano-N'-[4-(imidazol-4-yl)-phenyl]-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

• Imidazolylphenyl amidines, pharmaceutical compositions containing same
  申请人：Istituto de Angeli S.p.A.

  公开号：US04386099A1

  公开（公告）日：1983-05-31

  This invention relates to imidazolylphenyl amidines, the preparation thereof, and pharmaceutical compositions containing them. More particularly, this invention relates to compounds of the general formula ##STR1## in which R, R.sub.1, R.sub.3, which may be the same or different, each represent a hydrogen atom or a lower alkyl group, and R.sub.2 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, methyl, methoxy, or methylenedioxy groups, or a substituted or unsubstituted heterocyclylalkyl or heterocyclic group which may also contain a further hetero atom, or a non-toxic, pharmacologically acceptable acid addition salt thereof. These compounds are useful in treating disorders of the gastrointestinal tract.

  这项发明涉及咪唑基苯基脒，其制备方法以及含有它们的药物组合物。更具体地说，这项发明涉及一般式##STR1##中的化合物，其中R、R.sub.1、R.sub.3，它们可能相同也可能不同，分别代表氢原子或较低的烷基基团，R.sub.2代表线性或支链烷基、烯基或炔基、氰基、羟基、取代或未取代的环烷基或环脂肪基、双环基、芳基或芳基，可选择地由卤素、甲基、甲氧基或亚甲氧基基团取代，或取代或未取代的杂环烷基或杂环基团，也可能包含进一步的杂原子，或其非毒性、药理学上可接受的酸盐。这些化合物在治疗胃肠道疾病方面具有用途。
• Formamidine derivatives and pharmaceutical use
  申请人：Istituto de Angeli S.p.A.

  公开号：US04666932A1

  公开（公告）日：1987-05-19

  Compounds of the formula ##STR1## wherein R is hydrogen or methyl; R.sub.1 is straight or branched alkyl of 1 to 6 carbon atoms, dimethyldioxolylmethyl, hydroxymethyldioxolylmethyl, hydroxy(alkyl of 1 to 6 carbon atoms), mono- or di-(alkoxy of 1 to 6 carbon atoms)(alkyl of 1 to 6 carbon atoms), (alkyl of 1 to 6 carbon atoms)thio- (alkyl of 1 to 6 carbon atoms), (alkoxy of 1 to 6 carbon atoms)(alkyl of 1 to 6 carbon atoms)thio-(alkyl of 1 to 6 carbon atoms), cyano(alkyl of 1 to 6 carbon atoms), di-lower alkyl-amino(alkyl of 1 to 6 carbon atoms), alkenyl, alkynyl, or cycloalkyl; R.sub.2 and R.sub.3 are each independently hydrogen, alkyl of 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms or halogen; and Z is imidazol-2-yl or imidazol-4-yl; provided however that, when R.sub.1 is straight or branched alkyl, alkenyl, alkynyl, cycloalkyl or cyano and R, R.sub.2 and R.sub.3 are hydrogen, Z is other than imidazol-4-yl; tautomers thereof and non-toxic, pharmacologically acceptable acid addition salts thereof. The compounds as well as their salts are useful as antiulcerogenics and gastric acid secretion inhibitors.

  化合物的公式为##STR1##其中R为氢或甲基; R.sub.1为1到6个碳原子的直链或支链烷基，二甲基二氧杂环戊烯甲基，羟甲基二氧杂环戊烯甲基，羟基（1到6个碳原子的烷基），单或双（1到6个碳原子的烷氧基）（1到6个碳原子的烷基），（1到6个碳原子的烷基）硫（1到6个碳原子的烷基），（1到6个碳原子的烷氧基）（1到6个碳原子的烷基）硫（1到6个碳原子的烷基），氰基（1到6个碳原子的烷基），二-低烷基氨基（1到6个碳原子的烷基），烯基，炔基或环烷基; R.sub.2和R.sub.3各自独立地为氢，1到3个碳原子的烷基，1到3个碳原子的烷氧基或卤素;以及Z为咪唑-2-基或咪唑-4-基;但是，当R.sub.1为直链或支链烷基，烯基，炔基，环烷基或氰基，而R，R.sub.2和R.sub.3为氢时，Z不是咪唑-4-基;它们的互变异构体和非毒性、药理学上可接受的酸盐也是有用的抗溃疡剂和胃酸分泌抑制剂。
• Imidazolylphenyl amidines
  申请人：Instituto de Angeli S.p.A.

  公开号：US04465841A1

  公开（公告）日：1984-08-14

  This invention relates to imidazolylphenyl amidines, the preparation thereof, and pharmaceutical compositions containing them. More particularly, this invention relates to compounds of the general formula ##STR1## in which R, R.sub.1, and R.sub.3, which may be the same or different, each represent a hydrogen atom or a lower alkyl group, and R.sub.2 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, methyl, methoxy, or methylenedioxy groups, or a substituted or unsubstituted heterocyclylalkyl or heterocyclic group which may also contain a further hetero atom, or a non-toxic, pharmacologically acceptable acid addition salt thereof. These compounds are useful in treating disorders of the gastrointestinal tract.

  本发明涉及咪唑苯基脲类化合物及其制备方法和含有它们的药物组合物。更具体地说，本发明涉及一般式为##STR1##其中，R、R.sub.1和R.sub.3可以相同也可以不同，分别代表氢原子或低碳基；R.sub.2代表线性或支链烷基、烯基或炔基、氰基、羟基、取代或未取代的环烷基或环烷基烷基、双环基、芳基或芳基烷基（可选取代卤素、甲基、甲氧基或亚甲二氧基基团）、取代或未取代的杂环基烷基或杂环基团（也可以含有另一个杂原子）或其非毒性、药理学上可接受的酸盐。这些化合物在治疗胃肠道疾病方面有用。
• Substituted heterocyclyl phenylformamidines, processes for their preparation and their pharmaceutical use
  申请人：ISTITUTO DE ANGELI S.p.A.

  公开号：EP0094727A2

  公开（公告）日：1983-11-23

  Object of the present invention are new pharmacologically active substituted heterocyclylphenylformamidines of formula in which A represents a hydrogen atom, an amino group which may be substituted by one or two alkyl groups having 1 to 3 carbon atoms or a saturated heterocyclic ring, R represents a hydrogen atom or a methyl group, R1 represents a linear or branched alkyl group which may contain 1 or 2 heteroatoms such as a sulfur, an oxygen or nitrogen atom or may form a substituted or an unsubstituted cyclic ring, an alkenyl group, an alkynyl group, a cycloalkyl group or a phenyl group, R2 and R3 which may be the same or different, represent a hydrogen atom, an alkyl or alkoxy group having 1 to 3 carbon atom or a halogen atom, m and n represent 0 or 1, Het represents a substituted or unsubstituted heterocyclic ring containing from 1 to 3 heteroatoms (except the imidazole ring when R1 is a linear or branched alkyl group not containing heteroatoms and R2 and R3 are both hydrogen atoms), tautomers thereof and acid addition salts of the aforesaid compounds. Processes for preparation of the compounds of formula (I) and their intermediates as well as pharmaceutical compositions containing them are also object of this invention. The new compounds are H2-receptor blocking agents, inhibit gastric acid secretion, and are useful antiulcer agents.

  本发明的目的是具有药理活性的新的取代杂环苯基甲脒，其式为 其中 A 代表氢原子、可被一个或两个具有 1 至 3 个碳原子的烷基或饱和杂环取代的氨基，R 代表氢原子或甲基，R1 代表直链或支链烷基，该烷基可含有 1 或 2 个杂原子，如硫原子、氧原子或氮原子，或可形成取代或未取代的环环、烯基、炔基、环烷基或苯基、R2和R3可以相同或不同，代表氢原子、具有1至3个碳原子的烷基或烷氧基或卤素原子，m和n代表0或1，Het代表含有1至3个杂原子的取代或未取代的杂环（当R1为不含杂原子的直链或支链烷基且R2和R3均为氢原子时，咪唑环除外）、其同系物以及上述化合物的酸加成盐。制备式（I）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。 新化合物是 H2 受体阻断剂，可抑制胃酸分泌，是有效的抗溃疡剂。
• Bazzano; Vavoni; Mondoni, European Journal of Medicinal Chemistry, 1986, vol. 21, # 1, p. 27 - 33
  作者：Bazzano、Vavoni、Mondoni、et al.

  DOI：——

  日期：——