4-(4,4-dibromobut-3-enyl)-1-(triphenylmethyl)imidazole | 209599-08-6

• 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-(4,4-dibromobut-3-enyl)-1-(triphenylmethyl)imidazole
• 英文别名: 4-(4,4-dibromobut-3-enyl)-1-tritylimidazole
• CAS: 209599-08-6
• 化学式: C₂₆H₂₂Br₂N₂
• 分子量: 522.282
• InChiKey: XIRWHNOSKHVZEG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.4
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 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-(4,4-dibromobut-3-enyl)-1-(triphenylmethyl)imidazole 在 正丁基锂 、 四甲基乙二胺 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 3.25h， 生成 4-Non-3-ynyl-1-trityl-1H-imidazole
  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：

  3-(1-三苯甲游基-1H-咪唑-4-基)丙烷-1-醇 在 草酰氯 、 二甲基亚砜 、 三乙胺 、 三苯基膦 作用下， 反应 3.5h， 生成 4-(4,4-dibromobut-3-enyl)-1-(triphenylmethyl)imidazole
  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

• 1H-4(5)-substituted imidazole derivatives
  申请人：Gliatech, Inc.

  公开号：US06448282B1

  公开（公告）日：2002-09-10

  The present invention provides, in its principal aspect, compounds of the general formula: where A is —NHCO—, —N(CH3)—CO—, —NHCH2—, —N(CH3)—CH2—, —COCH2—, —CH2CH2—, or —CH(OH)CH2—, X is H, CH3, NH2, NH(CH3), N(CH3)2, OCH3, or SH; R2 is hydrogen or a methyl or ethyl group; R3 is hydrogen or a methyl or ehtyl group; n is 0, 1, 2, 3, 4, 5 or 6; R1 is selected from the group consisting of (a) alkyl; (b) C3 to C8 cycloalkyl; (c) phenyl or substituted phenyl; (d) heterocyclic; (e) decahydronaphthalene and (f) octahydroindane; or R1 and X may be taken together to denote a 5,6 or 6,6 saturated bicycle ring structure. The compounds of the present invention have H3 histamine receptor antagonist activity. This invention also provides pharmaceutical compositions comprising a pharmaceutically acceptable carrier in combination with an effective amount of a compound of formula 1.0. The present invention also provides a method of treating conditions in which antagonism of histamine H3 receptors may of therapeutic importance.

  本发明主要提供一般式化合物，其中A为—NHCO—、—N(CH3)—CO—、—NHCH2—、—N(CH3)—CH2—、—COCH2—、—CH2CH2—或—CH(OH)CH2—，X为H、CH3、NH2、NH(CH3)、N(CH3)2、OCH3或SH；R2为氢或甲基或乙基基团；R3为氢或甲基或乙基基团；n为0、1、2、3、4、5或6；R1选自以下组成的群体：(a)烷基；(b)C3到C8环烷基；(c)苯基或取代苯基；(d)杂环；(e)十氢萘或(f)八氢萘；或R1和X可以一起表示为一个5,6或6,6饱和双环环状结构。本发明化合物具有H3组胺受体拮抗活性。本发明还提供了包括药用载体和一定量的1.0式化合物的药物组合物。本发明还提供了一种治疗组胺H3受体拮抗剂可能具有治疗重要性的疾病的方法。
• 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
• 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.