(E)-3-(1H-imidazol-4-yl)propyl 3,7-dimethylocta-2,6-dienylcarbamate | 1308816-39-8

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (E)-3-(1H-imidazol-4-yl)propyl 3,7-dimethylocta-2,6-dienylcarbamate
• 英文别名: (E)-3-(1H-Imidazol-4-yl)propyl3,7-dimethylocta-2,6-dienylcarbamate hydrogenmaleate；3-(1H-imidazol-5-yl)propyl N-[(2E)-3,7-dimethylocta-2,6-dienyl]carbamate
• CAS: 1308816-39-8
• 化学式: C₁₇H₂₇N₃O₂
• 分子量: 305.42
• InChiKey: ZWUFKVVEDTWJAT-OQLLNIDSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  22
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  67
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  香叶醇 在 甲烷 、 一水合肼 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醇 、 乙酸乙酯 、 乙腈 为溶剂， 反应 3.0h， 生成 (E)-3-(1H-imidazol-4-yl)propyl 3,7-dimethylocta-2,6-dienylcarbamate
  参考文献：
  名称：

  N-Alkenyl and cycloalkyl carbamates as dual acting histamine H3 and H4 receptor ligands

  摘要：

  Previous studies have shown that several imidazole derivatives posses affinity to histamine H-3 and H-4 receptors. Continuing our study on structural requirements responsible for affinity and selectivity for H-3/H-4 receptor subtypes, two series of 3-(1H-imidazol-4-yl) propyl carbamates were prepared: a series of unsaturated alkyl derivatives (1-9) and a series possessing a cycloalkyl group different distances to the carbamate moiety (10-13). The compounds were tested for their affinities at the human histamine H3 receptor, stably expressed in CHO-K1 cells. Compounds 1, 2, 5-7, 10-13 were investigated for their affinities at the human histamine H-4 receptor co-expressed with G alpha(i2) and G beta(1)gamma(2) subunits in Sf9 cells. To expand the pharmacological profile, compounds were further tested for their H3 receptor antagonist activity on guinea pig ileum and in vivo after oral administration to mice. All tested compounds exhibited good affinity for the human histamine H-3 receptor with K-i values in the range from 14 to 194 nM. All compounds were active in vivo after peroral administration (p.o.) to Swiss mice, thus demonstrating their ability to cross the blood-brain barrier. The most potent H-3 receptor ligand of these series was compound 5, 3-(1H-imidazol-4-yl) propyl pent-4-enylcarbamate with the highest affinity (K-i = 14 nM). Additionally, compound 3 showed remarkable central nervous system (CNS) H3R activity, increasing the N-tau-methylhistamine levels in mice with an ED50 value of 0.55 mg/kg, p.o. evidencing therefore, a twofold increase of inverse agonist/antagonist potency compared to the reference inverse agonist/antagonist thioperamide. In this study, the imidazole propyloxy carbamate moiety was kept constant. The different lipophilic moieties connected to the carbamate functionality in the eastern part of the molecule had a range of influences on the human H-4 receptor affinity (154-1326 nM). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.03.046

文献信息

• N-Alkenyl and cycloalkyl carbamates as dual acting histamine H3 and H4 receptor ligands
  作者：Małgorzata Więcek、Tim Kottke、Xavier Ligneau、Walter Schunack、Roland Seifert、Holger Stark、Jadwiga Handzlik、Katarzyna Kieć-Kononowicz

  DOI：10.1016/j.bmc.2011.03.046

  日期：2011.5

  Previous studies have shown that several imidazole derivatives posses affinity to histamine H-3 and H-4 receptors. Continuing our study on structural requirements responsible for affinity and selectivity for H-3/H-4 receptor subtypes, two series of 3-(1H-imidazol-4-yl) propyl carbamates were prepared: a series of unsaturated alkyl derivatives (1-9) and a series possessing a cycloalkyl group different distances to the carbamate moiety (10-13). The compounds were tested for their affinities at the human histamine H3 receptor, stably expressed in CHO-K1 cells. Compounds 1, 2, 5-7, 10-13 were investigated for their affinities at the human histamine H-4 receptor co-expressed with G alpha(i2) and G beta(1)gamma(2) subunits in Sf9 cells. To expand the pharmacological profile, compounds were further tested for their H3 receptor antagonist activity on guinea pig ileum and in vivo after oral administration to mice. All tested compounds exhibited good affinity for the human histamine H-3 receptor with K-i values in the range from 14 to 194 nM. All compounds were active in vivo after peroral administration (p.o.) to Swiss mice, thus demonstrating their ability to cross the blood-brain barrier. The most potent H-3 receptor ligand of these series was compound 5, 3-(1H-imidazol-4-yl) propyl pent-4-enylcarbamate with the highest affinity (K-i = 14 nM). Additionally, compound 3 showed remarkable central nervous system (CNS) H3R activity, increasing the N-tau-methylhistamine levels in mice with an ED50 value of 0.55 mg/kg, p.o. evidencing therefore, a twofold increase of inverse agonist/antagonist potency compared to the reference inverse agonist/antagonist thioperamide. In this study, the imidazole propyloxy carbamate moiety was kept constant. The different lipophilic moieties connected to the carbamate functionality in the eastern part of the molecule had a range of influences on the human H-4 receptor affinity (154-1326 nM). (C) 2011 Elsevier Ltd. All rights reserved.