4-((1S,2S)-2-ethynyl-cyclopropyl)-1-trityl-1H-imidazole | 223419-93-0

• 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: 4-((1S,2S)-2-ethynyl-cyclopropyl)-1-trityl-1H-imidazole
• 英文别名: (1S,2S)-4-(2-ethynylcyclopropyl)-1-(triphenylmethyl)imidazole；4-[(1S,2S)-2-ethynylcyclopropyl]-1-tritylimidazole
• CAS: 223419-93-0
• 化学式: C₂₇H₂₂N₂
• 分子量: 374.485
• InChiKey: SAWAYNUHKQYDOZ-OFVILXPXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  17.8
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  4-((1S,2S)-2-ethynyl-cyclopropyl)-1-trityl-1H-imidazole 在 盐酸 、 正丁基锂 、 四甲基乙二胺 作用下， 以 乙醇 为溶剂， 反应 1.25h， 生成 GT-2342
  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
• 作为产物：
  描述：

  反式尿刊酸 在 氢氧化钾 、 正丁基锂 、 硫酸 、 sodium hydride 、 二异丁基氢化铝 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 二异丙胺 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 二氯甲烷 、 氯仿 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 48.0h， 生成 4-((1S,2S)-2-ethynyl-cyclopropyl)-1-trityl-1H-imidazole
  参考文献：
  名称：

  有效的组胺H 3拮抗剂GT-2331的高效多重谱合成和绝对构型的重新评估

  摘要：

  GT-2331是一种有效的组胺H 3拮抗剂，已进入临床试验。描述了该化合物及其对映异构体的有效数克合成。文献报道GT-2331是4- [2-（5,5-二甲基己基-1-炔基）环丙基] -1 H-咪唑的右旋（+），更有效的对映异构体，其绝对构型为（1 R，2 R）-1。然而，我们发现4- [2-（5,5-二甲基己基-1-炔基）环丙基] -1 H-咪唑的右旋，更有效的对映异构体具有（1 S，2 S）绝对构型。我们建议重新考虑GT-2331的绝对配置。

  DOI：

  10.1021/jo035264t

文献信息

• Design, Synthesis, and Structure−Activity Relationships of Acetylene-Based Histamine H₃ Receptor Antagonists
  作者：Syed M. Ali、Clark E. Tedford、Rosilyn Gregory、Michael K. Handley、Stephen L. Yates、Walter W. Hirth、James G. Phillips

  DOI：10.1021/jm980310g

  日期：1999.3.1

  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.
• An Efficient Multigram Synthesis of the Potent Histamine H₃ Antagonist GT-2331 and the Reassessment of the Absolute Configuration
  作者：Huaqing Liu、Francis A. Kerdesky、Lawrence A. Black、Michael Fitzgerald、Rodger Henry、Timothy A. Esbenshade、Arthur A. Hancock、Youssef L. Bennani

  DOI：10.1021/jo035264t

  日期：2004.1.1

  GT-2331 is a potent histamine H3 antagonist which has entered clinical trials. Efficient multigram syntheses of this compound and its enantiomer are described. The literature reports that GT-2331 is the dextrorotatory (+), more potent, enantiomer of 4-[2-(5,5-dimethylhex-1-ynyl)cyclopropyl]-1H-imidazole with the absolute configuration of (1R,2R)-1. However, we found that the dextrorotatory, more potent

  GT-2331是一种有效的组胺H 3拮抗剂，已进入临床试验。描述了该化合物及其对映异构体的有效数克合成。文献报道GT-2331是4- [2-（5,5-二甲基己基-1-炔基）环丙基] -1 H-咪唑的右旋（+），更有效的对映异构体，其绝对构型为（1 R，2 R）-1。然而，我们发现4- [2-（5,5-二甲基己基-1-炔基）环丙基] -1 H-咪唑的右旋，更有效的对映异构体具有（1 S，2 S）绝对构型。我们建议重新考虑GT-2331的绝对配置。