N''-Cyano-N-methyl-N'-<4-(imidazol-4-yl)-butyl>-guanidin | 52378-57-1

• 英文名称: N''-Cyano-N-methyl-N'-<4-(imidazol-4-yl)-butyl>-guanidin
• 英文别名: 2-cyano-1-[4-(1H-imidazol-4-yl)butyl]-3-methylguanidine；VUF5420；N-cyano-N'-[4-(1(3)H-imidazol-4-yl)-butyl]-N''-methyl-guanidine；1-cyano-3-[4-(1H-imidazol-5-yl)butyl]-2-methylguanidine
• CAS: 52378-57-1
• 化学式: C₁₀H₁₆N₆
• 分子量: 220.277
• InChiKey: SESBNJZEWNWYQM-UHFFFAOYSA-N

物化性质

• 沸点：
  445.2±47.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  16
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  88.9
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  草酸 、 N''-Cyano-N-methyl-N'-<4-(imidazol-4-yl)-butyl>-guanidin 以 乙醚 、 乙醇 为溶剂， 生成 1-(4-(1H-imidazol-4-yl)butyl)-2-cyano-3-methylguanidine oxalate
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Cyanoguanidine-Type and Structurally Related Histamine H₄ Receptor Agonists

  摘要：

  Recently, we identified high-affinity human histamine H-3 (hH(3)R) and H-4 receptor (hH(4)R) ligands among a series of N-G-acylated imidazolylpropylguanidines, which were originally designed as histamine H-2 receptor (H2R) agonists. Aiming at selectivity for hH(4)R, the acylguanidine group was replaced with related moieties. Within a series of cyanoguanidines, 2-cyano-1-[4-(1H-imidazol-4-yl)butyl]-3-[(2-phenylthio)ethyl]guanidine (UR-PI376, 67) was identified as the most potent hH(4)R agonist (pEC(50) = 7.47, alpha = 0.93) showing negligible hH(1)R and hH(2)R activities and significant selectivity over the hH(3)R (pK(B) = 6.00, alpha = -0.28), as determined in steady-state GTPase assays using. membrane preparations of hH(x)R-expressing Sf9 cells. In contrast to previously described selective H4R agonists, this compound and other 3-substituted derivatives are devoid of agonistic activity at the other HR subtypes. Modeling of the binding mode of 67 suggests that the cyanoguanidine moiety forms charge-assisted hydrogen bonds not only with the conserved Asp-94 but also with the hH(4)R-specific Arg-341 residue. 2-Carbamoyl-1-[2-(1H-imidazol-4-yl)ethyl]-3-(3-phenylpropyl)guanidine (UR-PI97, 88) was unexpectedly identified as a highly potent and selective hH(3)R inverse agonist (pK(B) = 8.42, > 300-fold selectivity over the other HR subtypes).

  DOI：

  10.1021/jm900526h
• 作为产物：
  描述：

  1-cyano-3-methyl-2-phenylisourea 、 4-(1H-咪唑-5-基)丁烷-1-胺 以 乙腈 为溶剂， 反应 12.0h， 以77%的产率得到N''-Cyano-N-methyl-N'-<4-(imidazol-4-yl)-butyl>-guanidin
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Cyanoguanidine-Type and Structurally Related Histamine H₄ Receptor Agonists

  摘要：

  Recently, we identified high-affinity human histamine H-3 (hH(3)R) and H-4 receptor (hH(4)R) ligands among a series of N-G-acylated imidazolylpropylguanidines, which were originally designed as histamine H-2 receptor (H2R) agonists. Aiming at selectivity for hH(4)R, the acylguanidine group was replaced with related moieties. Within a series of cyanoguanidines, 2-cyano-1-[4-(1H-imidazol-4-yl)butyl]-3-[(2-phenylthio)ethyl]guanidine (UR-PI376, 67) was identified as the most potent hH(4)R agonist (pEC(50) = 7.47, alpha = 0.93) showing negligible hH(1)R and hH(2)R activities and significant selectivity over the hH(3)R (pK(B) = 6.00, alpha = -0.28), as determined in steady-state GTPase assays using. membrane preparations of hH(x)R-expressing Sf9 cells. In contrast to previously described selective H4R agonists, this compound and other 3-substituted derivatives are devoid of agonistic activity at the other HR subtypes. Modeling of the binding mode of 67 suggests that the cyanoguanidine moiety forms charge-assisted hydrogen bonds not only with the conserved Asp-94 but also with the hH(4)R-specific Arg-341 residue. 2-Carbamoyl-1-[2-(1H-imidazol-4-yl)ethyl]-3-(3-phenylpropyl)guanidine (UR-PI97, 88) was unexpectedly identified as a highly potent and selective hH(3)R inverse agonist (pK(B) = 8.42, > 300-fold selectivity over the other HR subtypes).

  DOI：

  10.1021/jm900526h