GT 2286

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: GT 2286
• 英文别名: 4-(6-cyclopentylhex-3-ynyl)imidazole；4-(6-Cyclopentyl-hex-3-ynyl)-1H-imidazole；5-(6-cyclopentylhex-3-ynyl)-1H-imidazole
• 化学式: C₁₄H₂₀N₂
• 分子量: 216.326
• InChiKey: XFHACGZTJUJXHB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  28.7
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  3-(1-三苯甲游基-1H-咪唑-4-基)丙烷-1-醇 在 盐酸 、 正丁基锂 、 草酰氯 、 四甲基乙二胺 、 二甲基亚砜 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 为溶剂， 反应 7.25h， 生成 GT 2286
  参考文献：
  名称：

  Design, Synthesis, and Structure−Activity Relationships of Acetylene-Based Histamine H₃ Receptor Antagonists

  摘要：

  New, potent, and selective histamine H-3 receptor antagonists have been synthesized by employing the use of (1) an appropriately positioned nonpolar acetylene spacer group, (2) either a two-carbon straight chain linker or a conformationally restricting trans-cyclopropane ring between the C-4 position of an imidazole headgroup and the acetylene spacer, and (3) a Topliss operational scheme for side-chain substitution for optimizing the hydrophobic domain. Compounds 9-18 are examples synthesized with the two-carbon straight chain linker, whereas 26-31 are analogues prepared by incorporation of the trans-(+/-)-cyclopropane at the C-4 position of an imidazole headgroup. Synthesis of both the (1R,2R)- and (1S,2S)-cyclopropyl enantiomers of the most potent racemic compound 31 (K-i = 0.33 +/- 0.13 nM) demonstrated a stereopreference in H-3 receptor binding affinity for the (1R,2R) enantiomer 32 (K-i = 0.18 +/- 0.04 nM) versus the (1S,2S) enantiomer 33 (K-i = 5.3 +/- 0.5 nM). (1R,2R)-4-(2-(5,5-Dimethylhex-1-ynyl)cyclopropyl)- imidazole (32) is one of the most potent histamine H-3 receptor antagonists reported to date.

  DOI：

  10.1021/jm980310g

文献信息

• New acetylene based histamine H3 receptor antagonists derived from the marine natural product verongamine
  作者：Syed M. Ali、Clark E. Tedford、Rosilyn Gregory、Stephen L. Yates、James G. Phillips

  DOI：10.1016/s0960-894x(98)00181-4

  日期：1998.5

  New histamine H-3 receptor antagonists were developed using an acetylene moiety as a replacement or the amide-oxime functionality of verongamine 5. Optimization of receptor binding was performed by following aliphatic Topliss tree guidelines. These new H-3 ligands demonstrate excellent blood-brain barrier penetration. (C) 1998 Elsevier Science Ltd. All rights reserved.
• US6166060A
  申请人：——

  公开号：US6166060A

  公开（公告）日：2000-12-26
• US6448282B1
  申请人：——

  公开号：US6448282B1

  公开（公告）日：2002-09-10