4-phenyl-4-[1-(phenylmethyl)-1H-imidazol-2-yl]piperidine | 516521-17-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-phenyl-4-[1-(phenylmethyl)-1H-imidazol-2-yl]piperidine
• 英文别名: 4-(1-benzylimidazol-2-yl)-4-phenylpiperidine
• CAS: 516521-17-8
• 化学式: C₂₁H₂₃N₃
• 分子量: 317.434
• InChiKey: QVPDDQUTTXHSGV-UHFFFAOYSA-N

物化性质

• 沸点：
  501.6±50.0 °C(Predicted)
• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  29.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-phenyl-4-[1-(phenylmethyl)-1H-imidazol-2-yl]piperidine 、 异氰酸酯 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 4-(1-benzyl-1H-imidazol-2-yl)-4-phenylpiperidine-1-carboxamide
  参考文献：
  名称：

  4-Phenyl-4-[1H-imidazol-2-yl]-piperidine derivatives, a novel class of selective δ-opioid agonists

  摘要：

  A novel series of 4-phenyl-4-[1H-imidazol-2-yl]-piperidine derivatives has been prepared and their synthesis described herein. In vitro affinities for delta-, mu-, and kappa-opioid receptors, as well as the functional activity in the [S-35]GTP gamma S assay are reported. The most potent and selective delta-opioid agonist 18a exhibited a K-i of 18 nM, and was > 258-fold and 28-fold selective over mu- and kappa-receptors, respectively; the compound is a full agonist with an EC50 value of 14 nM. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.09.025
• 作为产物：
  描述：

  4-(1-Benzyl-1H-imidazol-2-yl)-4-hydroxy-piperidine-1-carboxylic acid ethyl ester 、 苯 在 三氯化铝 作用下， 反应 1.0h， 以54%的产率得到4-phenyl-4-[1-(phenylmethyl)-1H-imidazol-2-yl]piperidine
  参考文献：
  名称：

  4-Phenyl-4-[1H-imidazol-2-yl]-piperidine derivatives, a novel class of selective δ-opioid agonists

  摘要：

  A novel series of 4-phenyl-4-[1H-imidazol-2-yl]-piperidine derivatives has been prepared and their synthesis described herein. In vitro affinities for delta-, mu-, and kappa-opioid receptors, as well as the functional activity in the [S-35]GTP gamma S assay are reported. The most potent and selective delta-opioid agonist 18a exhibited a K-i of 18 nM, and was > 258-fold and 28-fold selective over mu- and kappa-receptors, respectively; the compound is a full agonist with an EC50 value of 14 nM. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.09.025

文献信息

• Substituted 4-phenyl-4-[1h-imidazol-2-yl]-piperidine derivatives as selective non-peptide delta opiod agonists with antidepressant and anxiolytic activity
  申请人：Steckler Horst Wolfgang Thomas

  公开号：US20060287345A1

  公开（公告）日：2006-12-21

  The present invention relates to the use of 4-phenyl-4-[1H-imidazol-2-yl]-piperidine derivatives according to Formula (I) the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the tautomeric forms thereof and the N-oxide forms thereof as selective non-peptide δ-opioid agonists for use in the prevention and/or treatment of various central nervous system disorders, in particular as selective antidepressant and anxiolytic non-peptide δ-opioid agonists. In particular are claimed compounds according to Formula (I) in which A=B is C═O or SO 2 , X is a covalent bond, R 1 is allyloxy, alkyloxyalkyl, Ar or NR 9 R 10 , wherein R 9 and R 10 each independently are hydrogen or Ar; or A=B and R 1 together form a benzoxazolyl radical; p is zero, R 3 is benzyl optionally substituted with hydroxy, alkyl or alkyloxycarbonyl and R 4 and R 5 each are hydrogen.

  本发明涉及使用公式（I）中的4-苯基-4-[1H-咪唑-2-基]-哌啶衍生物及其药学上可接受的酸或碱盐、其立体化学异构体、互变异构体和N-氧化物形式作为选择性非肽δ-阿片受体激动剂，用于预防和/或治疗各种中枢神经系统疾病，尤其是作为选择性抗抑郁和抗焦虑的非肽δ-阿片受体激动剂。特别地，本发明要求公式（I）中A=B为C═O或SO2，X为共价键，R1为烯丙氧基、烷氧烷基、Ar或NR9R10，其中R9和R10各自独立地为氢或Ar；或者A=B且R1构成苯并噁唑基基团；p为零，R3为苄基，可选择性地取代羟基、烷基或烷氧羰基，而R4和R5各自为氢。
• Novel substituted 4-phenyl-4-{1h-imidazol-2-yl}-piperidine derivatives and their use as selective non-peptide delta opioid agonists
  申请人：——

  公开号：US20040260096A1

  公开（公告）日：2004-12-23

  The present invention relates to novel 4-phenyl-4-[ 1 H-imidazol-2-yl]-piperidine derivatives according to Formula (I) 1 the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the tautomeric forms thereof and the N-oxide forms thereof. In particular are claimed compounds according to Formula (I) in which A=B is C═O or SO 2 , X is a covalent bond, R 1 is alkyloxy, alkyloxyalkyl, Ar or NR 9 R 10 , wherein R 9 and R 10 each independently are hydrogen or Ar; or A=B and R 1 together form a benzoxazolyl radical; p is zero, R 3 is benzyl optionally substituted with hydroxy, alkyl or alkyloxycarbonyl and R 4 and R 5 each are hydrogen. The invention also relates to processes for the preparation of the compounds according to the invention and their use in medicine, in particular as selective non-peptide &dgr;-opioid agonists for use in the treatment of various pain conditions.

  本发明涉及新型 4-苯基-4-&lsqb； 1 H-咪唑-2-基]-哌啶衍生物。 1 其药学上可接受的酸或碱加成盐、其立体化学异构体形式、其同分异构体形式和其 N-氧化物形式。特别是根据式 (I) 所述的化合物，其中 A=B 是 C═O 或 SO 2 X为共价键，R 1 是烷氧基、烷氧基烷基、Ar 或 NR 9 R 10 其中 R 9 和 R 10 各自独立地为氢或 Ar；或 A=B 和 R 1 共同形成一个苯并恶唑基；p 为零，R 3 是任选被羟基、烷基或烷氧羰基取代的苄基，R 4 和 R 5 均为氢。本发明还涉及根据本发明制备化合物的工艺及其在医学中的用途，特别是作为选择性非肽类阿片激动剂用于治疗各种疼痛病症。
• Substituted 4-phenyl-4-[1h-imidazol-2-yl]-piperidine derivatives for reducing ischaemic damage
  申请人：Janssens Eduard Frans

  公开号：US20050004170A1

  公开（公告）日：2005-01-06

  The present invention relates to an agent for reducing ischaemic damage to an organ, in particular to a heart and a brain, pharmaceutical compositions comprising said agent and the use of said agent for the treatment of ischaemic diseases to the heart and the brain. The agent comprises a substituted 4-phenyl-4-[1H-imidazol-2-yl]-piperidine derivative according to Formula (I) the pharmaceutically acceptable acid or base addition salts thereof, the stereochemically isomeric forms thereof, the tautomeric forms thereof, the N-oxide forms thereof and the prodrugs thereof. In particular are claimed the compounds according to Formula (I) in which A=B is C═O or SO 2 , X is a covalent bond, R 1 is alkyloxy, alkyloxyalkyl, Ar or NR 9 R 10 , wherein R 9 and R 10 each independently are hydrogen or Ar; or A=B and R 1 together form a benzoxazolyl radical; p is zero, R 3 is benzyl optionally substituted with hydroxy, alkyl or alkyloxycarbonyl and R 4 and R 5 each are hydrogen. The use of said agents has important clinical ramifications with regard to the reduction of ischaemic damage to an organ in a mammal, in particular to a heart and/or a brain, the prevention of coronary artery diseases in a mammal by inducing a cardioprotective effect and the treatment and prevention of stroke.

  本发明涉及一种减少器官（尤其是心脏和大脑）缺血性损伤的制剂、包含所述制剂的药物组合物以及使用所述制剂治疗心脏和大脑缺血性疾病的方法。所述制剂包括符合式 (I) 的取代的 4-苯基-4-[1H-咪唑-2-基]-哌啶衍生物 其药学上可接受的酸或碱加成盐、其立体化学异构体形式、其同分异构体形式、其 N-氧化物形式和其原药。特别是根据式 (I) 所述的化合物，其中 A=B 是 C═O 或 SO 2 X为共价键，R 1 是烷氧基、烷氧基烷基、Ar 或 NR 9 R 10 其中 R 9 和 R 10 各自独立地为氢或 Ar；或 A=B 和 R 1 共同形成一个苯并恶唑基；p 为零，R 3 是任选被羟基、烷基或烷氧羰基取代的苄基，R 4 和 R 5 均为氢。上述制剂的使用在以下方面具有重要的临床意义：减少哺乳动物器官的缺血性损伤，特别是心脏和/或大脑；通过诱导心脏保护作用预防哺乳动物的冠状动脉疾病；治疗和预防中风。
• SUBSTITUTED 4-PHENYL-4-(1H-IMIDAZOL-2-YL)-PIPERIDINE DERIVATIVES FOR REDUCING ISCHAEMIC DAMAGE
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP1438049A2

  公开（公告）日：2004-07-21
• NOVEL SUBSTITUTED 4-PHENYL-4- 1H-IMIDAZOL-2-YL]-PIPERIDINE DERIVATIVES AND THEIR USE AS SELECTIVE NON-PEPTIDE DELTA OPIOID AGONISTS
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP1438304A1

  公开（公告）日：2004-07-21