1-(tert-butoxycarbonyl)-2-(2-phenylethylsulfonyl)-1-[3-(1-trityl-1H-imidazol-4-yl)propyl]guanidine | 1192560-17-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 1-(tert-butoxycarbonyl)-2-(2-phenylethylsulfonyl)-1-[3-(1-trityl-1H-imidazol-4-yl)propyl]guanidine
• 英文别名: tert-butyl N-[N-(2-phenylethylsulfonyl)-N'-[3-(1-tritylimidazol-4-yl)propyl]carbamimidoyl]carbamate
• CAS: 1192560-17-0
• 化学式: C₃₉H₄₃N₅O₄S
• 分子量: 677.868
• InChiKey: ITTCACOJUVYKPZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  49
• 可旋转键数：
  16
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  123
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(tert-butoxycarbonyl)-2-(2-phenylethylsulfonyl)-1-[3-(1-trityl-1H-imidazol-4-yl)propyl]guanidine 、 三氟乙酸 以 二氯甲烷 为溶剂， 反应 5.0h， 以71%的产率得到1-[3-(1H-imidazol-4-yl)propyl]-2-(2-phenylethylsulfonyl)guanidine trifluoroacetate
  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：

  N1-(tert-butoxycarbonyl)-N2-[3-(1-trityl-1H-imidazol-4-yl)propyl]guanidine 、 2-苯基-乙烷磺酰氯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以50%的产率得到1-(tert-butoxycarbonyl)-2-(2-phenylethylsulfonyl)-1-[3-(1-trityl-1H-imidazol-4-yl)propyl]guanidine
  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

文献信息

• Synthesis and Structure−Activity Relationships of Cyanoguanidine-Type and Structurally Related Histamine H₄ Receptor Agonists
  作者：Patrick Igel、Roland Geyer、Andrea Strasser、Stefan Dove、Roland Seifert、Armin Buschauer

  DOI：10.1021/jm900526h

  日期：2009.10.22

  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).