4-(3-(2-(3-nitrophenyl)-2-oxoethoxy)propyl)-1H-imidazole

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-(3-(2-(3-nitrophenyl)-2-oxoethoxy)propyl)-1H-imidazole
• 英文别名: 2-(3-(1H-Imidazol-4-yl)propyloxy)-1-(3-nitrophenyl)ethanone；2-[3-(1H-imidazol-5-yl)propoxy]-1-(3-nitrophenyl)ethanone
• 化学式: C₁₄H₁₅N₃O₄
• 分子量: 289.291
• InChiKey: ZLHIXLXTEUNBFV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-溴-3'-硝基苯乙酮 在 盐酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 4-(3-(2-(3-nitrophenyl)-2-oxoethoxy)propyl)-1H-imidazole
  参考文献：
  名称：

  4-(ω-(Alkyloxy)alkyl)-1H-imidazole Derivatives as Histamine H₃ Receptor Antagonists/Agonists

  摘要：

  In an effort to develop new histamine H-3 receptor antagonists usable as pharmacological tools we present here novel unsymmetrical ether derivatives. Etherification of different omega-(1H-imidazol-4-yl)alkyl scaffolds led to compounds containing alkyl chains of increasing lengths either with or without unsaturated termini, cycloalkyl or arylalkyl moieties, or additional heteroatoms. When investigated in an in vitro assay on rat synaptosomes, the majority of compounds displayed potencies in the low nanomolar concentration range at the H-3 receptor, e.g., 4-(3-(3-cyclopentylpropyloxy)propyl)-1H-imidazole (27, K-i = 7 nM). FUB 465, 4-(3-(ethoxy)propyl)-1H-imidazole (14), a useful tool for the characterization of constitutive activity of H-3 receptors in vivo in rodents, proved to be of high oral in vivo potency in mice (ED50 = 0.26 mg/kg). Further, the influence of chosen compounds on specific [S-35]GTPgammaS binding was assayed on HEK293 cell membranes expressing the human histamine H-3 receptor revealing partial agonism of the compounds in this particular model. These distinct responses are further hints for "protean agonism" in this class of compounds. Additionally, selected compounds were functionally investigated in vitro on isolated organs of the guinea-pig at H-3, H-1, and H-2 receptors.

  DOI：

  10.1021/jm031065q

文献信息

• Imidazole derivatives as histamine receptor H3 (ANT) agonists
  申请人：Institut National de la Sante et de la Recherche Medical

  公开号：US06248765B1

  公开（公告）日：2001-06-19

  Novel imidazole derivatives as histamine receptor H3 antagonists and/or agonists, preparation thereof and therapeutical uses thereof. Chemical compounds for use as histamine receptor H3 agonists, partial agonists or antagonists, having general formula (Ia) or (Ib), the use thereof for making drugs, and methods for revealing the agonist, partial agonist or antagonist activity of such compounds in vivo, are disclosed.

  新型咪唑衍生物作为组胺受体H3拮抗剂和/或激动剂，其制备和治疗用途。用作组胺受体H3激动剂、部分激动剂或拮抗剂的化合物，具有通式(Ia)或(Ib)，其用于制备药物的用途，并公开了在体内揭示这类化合物的激动剂、部分激动剂或拮抗剂活性的方法。
• US6248765B1
  申请人：——

  公开号：US6248765B1

  公开（公告）日：2001-06-19
• 4-(<i>ω</i>-(Alkyloxy)alkyl)-1<i>H</i>-imidazole Derivatives as Histamine H₃ Receptor Antagonists/Agonists
  作者：Galina Meier、Michael Krause、Annette Hüls、Xavier Ligneau、Heinz H. Pertz、Jean-Michel Arrang、C. Robin Ganellin、Jean-Charles Schwartz、Walter Schunack、Holger Stark

  DOI：10.1021/jm031065q

  日期：2004.5.1

  In an effort to develop new histamine H-3 receptor antagonists usable as pharmacological tools we present here novel unsymmetrical ether derivatives. Etherification of different omega-(1H-imidazol-4-yl)alkyl scaffolds led to compounds containing alkyl chains of increasing lengths either with or without unsaturated termini, cycloalkyl or arylalkyl moieties, or additional heteroatoms. When investigated in an in vitro assay on rat synaptosomes, the majority of compounds displayed potencies in the low nanomolar concentration range at the H-3 receptor, e.g., 4-(3-(3-cyclopentylpropyloxy)propyl)-1H-imidazole (27, K-i = 7 nM). FUB 465, 4-(3-(ethoxy)propyl)-1H-imidazole (14), a useful tool for the characterization of constitutive activity of H-3 receptors in vivo in rodents, proved to be of high oral in vivo potency in mice (ED50 = 0.26 mg/kg). Further, the influence of chosen compounds on specific [S-35]GTPgammaS binding was assayed on HEK293 cell membranes expressing the human histamine H-3 receptor revealing partial agonism of the compounds in this particular model. These distinct responses are further hints for "protean agonism" in this class of compounds. Additionally, selected compounds were functionally investigated in vitro on isolated organs of the guinea-pig at H-3, H-1, and H-2 receptors.