2-(tert-butyldimethylsilyl)-5-(8-chlorooctyl)-1-(N,N-dimethylsulfamoyl)imidazole | 160815-37-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(tert-butyldimethylsilyl)-5-(8-chlorooctyl)-1-(N,N-dimethylsulfamoyl)imidazole
• 英文别名: 2-[tert-butyl(dimethyl)silyl]-5-(8-chlorooctyl)-N,N-dimethylimidazole-1-sulfonamide
• CAS: 160815-37-2
• 化学式: C₁₉H₃₈ClN₃O₂SSi
• 分子量: 436.134
• InChiKey: QBFAQZQJKOJCOZ-UHFFFAOYSA-N

物化性质

• 沸点：
  509.855±52.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.079±0.14 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.38
• 重原子数：
  27
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  63.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(tert-butyldimethylsilyl)-5-(8-chlorooctyl)-1-(N,N-dimethylsulfamoyl)imidazole 在 盐酸 、 氢溴酸 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 65.0h， 生成 4-(8-Pyrrolidin-1-yl-octyl)-1H-imidazole
  参考文献：
  名称：

  Synthesis and Pharmacological Identification of Neutral Histamine H₁-Receptor Antagonists

  摘要：

  In the present study we searched for neutral antagonists for the human histamine H-1-receptor (H,R) by screening newly synthesized ligands that are structurally related to H1R agonists for their affinity using radioligand displacement studies and by assessing their functional activity via performing a NF-kappaB driven reporter-gene assay that allows for the detection of both agonistic and inverse agonistic responses. Starting from the endogenous agonist for the H1R, histamine, we synthesized and tested various analogues and ultimately identified several compounds with partial inverse agonistic properties and two neutral Hi-receptor antagonists, namely 2-[2-(4,4diphenylbutyl)-1H-imidazol-4-yl]ethylamine (histabudifen, 18d) (pK(i) = 5.8, alpha = 0.02) and 2-[2-(5,5-diphenylpentyl)-1H-imidazol-4-yl]ethylamine (histapendifen, 18e) (pK(i) = 5.9, alpha = -0.09).

  DOI：

  10.1021/jm030936t
• 作为产物：
  描述：

  N,N-二甲基咪唑-1-磺酰胺 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 1.25h， 生成 2-(tert-butyldimethylsilyl)-5-(8-chlorooctyl)-1-(N,N-dimethylsulfamoyl)imidazole
  参考文献：
  名称：

  Synthesis and Pharmacological Identification of Neutral Histamine H₁-Receptor Antagonists

  摘要：

  In the present study we searched for neutral antagonists for the human histamine H-1-receptor (H,R) by screening newly synthesized ligands that are structurally related to H1R agonists for their affinity using radioligand displacement studies and by assessing their functional activity via performing a NF-kappaB driven reporter-gene assay that allows for the detection of both agonistic and inverse agonistic responses. Starting from the endogenous agonist for the H1R, histamine, we synthesized and tested various analogues and ultimately identified several compounds with partial inverse agonistic properties and two neutral Hi-receptor antagonists, namely 2-[2-(4,4diphenylbutyl)-1H-imidazol-4-yl]ethylamine (histabudifen, 18d) (pK(i) = 5.8, alpha = 0.02) and 2-[2-(5,5-diphenylpentyl)-1H-imidazol-4-yl]ethylamine (histapendifen, 18e) (pK(i) = 5.9, alpha = -0.09).

  DOI：

  10.1021/jm030936t

文献信息

• Homologs of Histamine as Histamine H3 Receptor Antagonists: A New Potent and Selective H3 Antagonist, 4(5)-(5-Aminopentyl)-1H-imidazole
  作者：Roeland C. Vollinga、Wiro M. P. B. Menge、Rob Leurs、Hendrik Timmerman

  DOI：10.1021/jm00002a008

  日期：1995.1

  The influence of alkyl chain length variation on the histamine H-3 receptor activity of histamine homologs 1 was investigated. A series of 4(5)-(omega-aminoalkyl)-1H-imidazoles 1 was prepared with an alkyl chain length varying from one methylene group to 10 methylene groups. Besides the H-3 activity, the affinities of these compounds for the H-1 and H-2 receptors were determined. The ethylene chain of histamine is optimal for agonistic activity on all three histamine receptor subtypes. For the H-3 receptor, elongation of the alkyl chain from three methylene groups on leads to compounds with antagonistic properties. 4(5)-(5-Aminopentyl)-1H-imidazole (impentamine, 1e) is the most potent and selective H-3 antagonist from this series of 4(5)-(omega-aminoalkyl)-1H-imidazoles 1, with a pA(2) value of 8.4 (on guinea pig jejunum). A specific antagonistic binding site for this compound is proposed.
• Synthesis and Pharmacological Identification of Neutral Histamine H₁-Receptor Antagonists
  作者：Marinella Govoni、Remko A. Bakker、Ineke van de Wetering、Martine J. Smit、Wiro M. B. P. Menge、Henk Timmerman、Sigurd Elz、Walter Schunack、Rob Leurs

  DOI：10.1021/jm030936t

  日期：2003.12.1

  In the present study we searched for neutral antagonists for the human histamine H-1-receptor (H,R) by screening newly synthesized ligands that are structurally related to H1R agonists for their affinity using radioligand displacement studies and by assessing their functional activity via performing a NF-kappaB driven reporter-gene assay that allows for the detection of both agonistic and inverse agonistic responses. Starting from the endogenous agonist for the H1R, histamine, we synthesized and tested various analogues and ultimately identified several compounds with partial inverse agonistic properties and two neutral Hi-receptor antagonists, namely 2-[2-(4,4diphenylbutyl)-1H-imidazol-4-yl]ethylamine (histabudifen, 18d) (pK(i) = 5.8, alpha = 0.02) and 2-[2-(5,5-diphenylpentyl)-1H-imidazol-4-yl]ethylamine (histapendifen, 18e) (pK(i) = 5.9, alpha = -0.09).