4-[2-(imidazol-4-yl)ethyl]piperidine

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 4-[2-(imidazol-4-yl)ethyl]piperidine
• 英文别名: 4-[2-(1H-imidazol-5-yl)ethyl]piperidine
• 化学式: C₁₀H₁₇N₃
• 分子量: 179.265
• InChiKey: XSOYKCANSOSZRB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  40.7
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  3-(1-Benzyl-piperidin-4-yl)-propan-1-ol 在 palladium on activated charcoal 草酰氯 、 氰化钠 、 氨 、 甲酸铵 、 二甲基亚砜 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 29.75h， 生成 4-[2-(imidazol-4-yl)ethyl]piperidine
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of Conformationally Constrained Histamine H₃ Receptor Agonists

  摘要：

  Immepip, a conformationally constrained analogue of the histamine congener imbutamine, shows high affinity and functional activity on the human H-3 receptor. Using histamine and its homologues as prototypes, other rigid analogues containing either a piperidine or pyrrolidine ring in the side chain were synthesized and tested for their activities at the human H-3 receptor and the closely related H-4 receptor. In the series of piperidine containing analogues, immepip was found to be the most potent H-3 receptor agonist, whereas its propylene analogue 13a was identified as a high-affinity neutral antagonist for the human H-3 receptor. Moreover, replacement of the piperidine ring of immepip by a pyrrolidine ring led to a pair of enantiomers that show a distinct stereoselectivity at the human H-3 and H-4 receptor.

  DOI：

  10.1021/jm030905y

文献信息

• An Efficient and Convenient Synthesis of 4-Vinylimidazoles Using a Novel Horner-Wadsworth-Emmons (HWE) Reagent: Synthetic Studies Toward Novel Histamine H3-Ligands
  作者：Shinya Harusawa、Shuji Koyabu、Yasutoshi Inoue、Yasuhiko Sakamoto、Lisa Araki、Takushi Kurihara

  DOI：10.1055/s-2002-31951

  日期：——

  A novel Horner-Wadsworth-Emmons (HWE)-type reagent 1 reacted readily with various aldehydes and ketones to produce (E)-vinylimidazoles 2 in good yields. The synthetic utility of 1 was demonstrated by the efficient preparation of four histamine H 3 ligands 3 by simple hydrogenation of 2.

  一种新型的 Horner-Wadsworth-Emmons (HWE) 型试剂 1 很容易与各种醛和酮反应，以良好的收率生产 (E)-乙烯基咪唑 2。1 的合成效用通过简单氢化 2 有效制备四种组胺 H 3 配体 3 得到证明。
• <i>N</i>-Substituted Piperidinyl Alkyl Imidazoles:  Discovery of Methimepip as a Potent and Selective Histamine H₃ Receptor Agonist
  作者：Ruengwit Kitbunnadaj、Takeshi Hashimoto、Enzo Poli、Obbe P. Zuiderveld、Alessandro Menozzi、Ryoko Hidaka、Iwan J. P. de Esch、Remko A. Bakker、Wiro M. P. B. Menge、Atsushi Yamatodani、Gabriella Coruzzi、Henk Timmerman、Rob Leurs

  DOI：10.1021/jm049475h

  日期：2005.3.1

  efforts toward the development of potent and highly selective histamine H(3) receptor agonists. We introduced various alkyl or aryl alkyl groups on the piperidine nitrogen of the known H(3)/H(4) agonist immepip and its analogues (1-3a). We observed that N-methyl-substituted immepip (methimepip) exhibits high affinity and agonist activity at the human histamine H(3) receptor (pK(i) = 9.0 and pEC(50) = 9

  在这项研究中，我们继续努力发展有效和高度选择性的组胺H（3）受体激动剂。我们在已知的H（3）/ H（4）激动剂impipip及其类似物（1-3a）的哌啶氮上引入了各种烷基或芳基烷基。我们观察到N-甲基取代的immepip（methimepip）对人类组胺H（3）受体（pK（i）= 9.0和pEC（50）= 9.5）表现出高亲和力和激动剂活性，在该处的选择性是2000倍。人类H（3）受体超过人类H（4）受体，选择性超过人类H组胺H（1）和H（2）受体的10000倍以上。Methimepip在豚鼠回肠中作为H（3）受体激动剂也非常有效（pD（2）= 8.26）。而且，
• Production of imidazole derivatives and novel intermediates of the derivatives
  申请人：Sakamoto Yasuhiko

  公开号：US20050043277A1

  公开（公告）日：2005-02-24

  An improvement in the production of imidazole derivatives including histamine H 3 agonist immepip and histamine H 3 antagonist VUF4929. Desired imidazole derivatives can be easily obtained in high yield by using novel intermediates represented by the general formula (I): (I) wherein R 1 is an amino-protecting group; R 2 and R 3 are each independently hydrogen, lower alkyl, or hydroxylated lower alkyl; R 4 is lower alkyl, halogenated lower alkyl, or substituted or unsubstituted phenyl; and A is C 1-3 alkylene.

  生产咪唑衍生物，包括组胺H3激动剂immepip和组胺H3拮抗剂VUF4929的方法得到了改进。使用由通式（I）表示的新型中间体，可以轻松地高产得到所需的咪唑衍生物：（I）其中，R1是氨基保护基；R2和R3各自独立地是氢、低碳基或羟基化的低碳基；R4是低碳基、卤代低碳基或取代或未取代的苯基；A是C1-3烷基。
• IMPROVEMENT IN THE PRODUCTION OF IMIDAZOLE DERIVATIVES AND NOVEL INTERMEDIATES OF THE DERIVATIVES
  申请人：Azwell Inc.

  公开号：EP1477487A1

  公开（公告）日：2004-11-17

  The invention provides an improvement in the production of imidazole derivatives including histamine H3 agonist immepip and histamine H3 antagonist VUF4929. Desired imidazole derivatives can be easily obtained in high yield by using novel intermediates represented by the general formula (I): wherein R1 is an amino-protecting group; R2 and R3 are each independently hydrogen, lower alkyl, or hydroxy-(lower alkyl); R4 is lower alkyl, halogenated lower alkyl, or substituted or unsubstituted phenyl; and A is C1-3 alkylene.

  本发明改进了组胺 H3 激动剂 immepip 和组胺 H3 拮抗剂 VUF4929 等咪唑衍生物的生产工艺。利用通式 (I) 所代表的新型中间体，可以很容易地以高产率获得所需的咪唑衍生物： 其中 R1 是氨基保护基团；R2 和 R3 各自独立地是氢、低级烷基或羟基-（低级烷基）；R4 是低级烷基、卤代低级烷基或取代或未取代的苯基；A 是 C1-3 亚烷基。
• US6951944B2
  申请人：——

  公开号：US6951944B2

  公开（公告）日：2005-10-04