1-[1-triphenylmethyl-1H-imidazol-4-yl]-6-cyclohexyl-3-hexyne | 223419-71-4

• 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: 1-[1-triphenylmethyl-1H-imidazol-4-yl]-6-cyclohexyl-3-hexyne
• 英文别名: 4-(6-cyclohexylhex-3-ynyl)-1-tritylimidazole
• CAS: 223419-71-4
• 化学式: C₃₄H₃₆N₂
• 分子量: 472.673
• InChiKey: NQTNCYZXQBETIP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.3
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 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：

  1-[1-triphenylmethyl-1H-imidazol-4-yl]-6-cyclohexyl-3-hexyne 在 盐酸 作用下， 反应 2.0h， 生成 GT 2260
  参考文献：
  名称：

  New acetylene based histamine H3 receptor antagonists derived from the marine natural product verongamine

  摘要：

  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.

  DOI：

  10.1016/s0960-894x(98)00181-4
• 作为产物：
  描述：

  3-(1-三苯甲游基-1H-咪唑-4-基)丙醛 在 正丁基锂 、 四甲基乙二胺 、 三苯基膦 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 6.58h， 生成 1-[1-triphenylmethyl-1H-imidazol-4-yl]-6-cyclohexyl-3-hexyne
  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：US06166060A1

  公开（公告）日：2000-12-26

  The present invention provides, in its principal aspect, compounds of the general formula: ##STR1## when A is --NHCO--, --N(CH.sub.3)--CO--, --NHCH.sub.2 --, --N(CH.sub.3)--CH.sub.2 --, --CH.dbd.CH--, --COCH.sub.2 --, CH.sub.2 CH.sub.2 --, --CH(OH)CH.sub.2 -- or --C.tbd.C--; X can be H, CH.sub.3, NH.sub.2, NH(CH.sub.3),N(CH.sub.3).sub.2, OH, OCH.sub.3, SH, R.sub.2 is hydrogen or a methyl or ethyl group; R.sub.3 is hydrogen or a methyl or ethyl group; n is 0, 1, 2, 3, 4, 5 or 6; R.sub.1 is selected from the group consisting of (a) alkyl; (b) C.sub.3 to C.sub.8 cycloalkyl; (c) phenyl or substituted phenyl; (d) heteroocyclic; and (f) decahydronaphthalene or octahydroindane; and When R.sub.1 and X taken together denote a 5, 6 or 6, 6 saturated bicyclic ring structure, X can be NH, O, S, SO.sub.2, When X is constrained in a 5, 6 or 6, 6, saturated bicyclic ring structure, then for example, when X.dbd.NH, R.sub.1 and X taken together mean an octahydroindole ring structure directly attached to A.

  本发明在其主要方面提供了一般式化合物：##STR1## 当A为--NHCO--，--N(CH.sub.3)--CO--，--NHCH.sub.2--，--N(CH.sub.3)--CH.sub.2--，--CH.dbd.CH--，--COCH.sub.2--，CH.sub.2CH.sub.2--，--CH(OH)CH.sub.2--或--C.tbd.C--；X可以是H，CH.sub.3，NH.sub.2，NH(CH.sub.3)，N(CH.sub.3).sub.2，OH，OCH.sub.3，SH，R.sub.2为氢或甲基或乙基基团；R.sub.3为氢或甲基或乙基基团；n为0, 1, 2, 3, 4, 5或6；R.sub.1选自（a）烷基；（b）C.sub.3至C.sub.8环烷基；（c）苯基或取代苯基；（d）杂环；和（f）去氢萘或八氢萘；当R.sub.1和X一起表示5, 6或6, 6饱和的双环环结构时，X可以是NH，O，S，SO.sub.2，当X被约束在5, 6或6, 6饱和的双环环结构中时，例如，当X.dbd.NH时，R.sub.1和X一起表示直接连接到A的八氢吲哚环结构。
• 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
• 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.
• 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.