1-(4-chloro-phenyl)-2-(2,4-dichloro-phenyl)-5-hydroxymethyl-1H-imidazole-4-carboxylic acid piperidin-1-ylamide | 847474-69-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(4-chloro-phenyl)-2-(2,4-dichloro-phenyl)-5-hydroxymethyl-1H-imidazole-4-carboxylic acid piperidin-1-ylamide
• 英文别名: 1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-(hydroxymethyl)-N-piperidin-1-yl-1H-imidazole-4-carboxamide；1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-hydroxymethyl-N-(piperidin-1-yl)-1H-imidazole-4-carboxamide；1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-(hydroxymethyl)-N-(piperidin-1-yl)-1H-imidazole-4-carboxamide；1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-(hydroxymethyl)-N-piperidin-1-ylimidazole-4-carboxamide
• CAS: 847474-69-5
• 化学式: C₂₂H₂₁Cl₃N₄O₂
• 分子量: 479.793
• InChiKey: PHWDIDWKGGEYRL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  70.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-hydroxymethyl-1H-imidazole-4-carboxylic acid 、 1-氨基哌啶 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以37%的产率得到1-(4-chloro-phenyl)-2-(2,4-dichloro-phenyl)-5-hydroxymethyl-1H-imidazole-4-carboxylic acid piperidin-1-ylamide
  参考文献：
  名称：

  1 H-imidazole derivatives having CB1 agonistic, CB1 partial agonistic or CB1-antagonistic activity

  摘要：

  本发明涉及一组新颖的1H-咪唑衍生物，以及制备这些化合物的方法和含有这些化合物中的一个或多个作为活性成分的药物组合物。这些1H-咪唑衍生物是有效的大麻素-CB1受体激动剂、部分激动剂或拮抗剂，可用于治疗精神疾病和神经系统疾病，以及其他涉及大麻素神经传递的疾病。这些化合物具有通式（I），其中R和R1-R4的含义如规范中所述。

  公开号：

  US20050054679A1

文献信息

• Pharmaceutical compositions comprising CB1 cannabinoid receptor antagonists and potassium channel openers for the treatment of obesity and related conditions
  申请人：Firnges Michael

  公开号：US20060128673A1

  公开（公告）日：2006-06-15

  Described is a novel combination therapy for diabetes mellitus type I and/or for obesity and its concomitant and/or secondary diseases or conditions, in particular the metabolic syndrome and/or syndrome X, and/or diabetes mellitus type II, by administering a combination of at least one K ATP channel opener as a first active agent and at least one CB 1 cannabinoid receptor antagonist as a second active agent. The invention is further directed to such novel combination therapy wherein a dually acting compound with combined K ATP channel opening and CB 1 antagonistic properties is used. The invention also relates to novel pharmaceutical compositions comprising K ATP channel openers and CB 1 antagonists and the use of said pharmaceutical compositions in the treatment, delayed progression, delayed onset of and/or inhibition of diabetes mellitus type 1, and the prophylaxis and treatment, of obesity as well as the prophylaxis, treatment, delayed onset and/or inhbition of its concomitant and/or secondary diseases or conditions, in particular the metabolic syndrome and/or syndrome X, and/or diabetes mellitus type II, in mammals and humans. The invention is further directed to such novel pharmaceutical compositions comprising a dually acting compound with combined K ATP channel opening and CB 1 antagonistic properties.

  所述的是一种新型组合疗法，用于治疗 I 型糖尿病和/或肥胖症及其伴随和/或继发疾病或病症，特别是代谢综合征和/或 X 综合征和/或 II 型糖尿病，其方法是给药至少一种 K ATP 通道开启剂作为第一活性剂与至少一种 CB 1 大麻素受体拮抗剂作为第二活性制剂。本发明进一步涉及这种新型组合疗法，其中一种双重作用的化合物联合 K ATP 通道开放和 CB 1 拮抗特性的双重作用化合物。本发明还涉及包含 K ATP 通道开启剂和 CB 1 拮抗剂的新型药物组合物，以及将所述药物组合物用于治疗、延缓进展、延缓发病和/或抑制 1 型糖尿病，预防和治疗肥胖症，以及预防、治疗、延缓发病和/或抑制其伴随和/或继发疾病或病症，特别是哺乳动物和人类的代谢综合征和/或 X 综合征和/或 II 型糖尿病。本发明进一步涉及这种新型药物组合物，其中包含一种具有联合 K ATP 通道开放和 CB 1 拮抗特性的双重作用化合物。
• Probing the cannabinoid CB1/CB2 receptor subtype selectivity limits of 1,2-diarylimidazole-4-carboxamides by fine-tuning their 5-substitution pattern
  作者：Jos H.M. Lange、Martina A.W. van der Neut、Alice J.M. Borst、Mahmut Yildirim、Herman H. van Stuivenberg、Bernard J. van Vliet、Chris G. Kruse

  DOI：10.1016/j.bmcl.2010.03.068

  日期：2010.5

  The cannabinoid CB1/CB2 receptor subtype selectivity in the 1,2-diarylimidazole-4-carboxamide series was boosted by fine-tuning its 5-substitution pattern. The presence of the 5-methylsulfonyl group in 11 led to a greater than similar to 840-fold CB1/CB2 subtype selectivity. The compounds 10, 18 and 19 were found more active than rimonabant (1) in a CB1-mediated rodent hypotension model after oral administration. Our findings suggest a limited brain exposure of the P-glycoprotein substrates 11, 12 and 21. (C) 2010 Elsevier Ltd. All rights reserved.
• USE OF CBX CANNABINOID RECEPTOR MODULATORS AS POTASSIUM CHANNEL MODULATORS
  申请人：Solvay Pharmaceuticals GmbH

  公开号：EP2012775A1

  公开（公告）日：2009-01-14
• PHARMACEUTICAL COMPOSITIONS COMPRISING CBX CANNABINOID RECEPTOR MODULATORS AND POTASSIUM CHANNEL MODULATORS
  申请人：Solvay Pharmaceuticals GmbH

  公开号：EP2026798A1

  公开（公告）日：2009-02-25
• Use of CBx cannabinoid receptor modulators as potassium channel modulators
  申请人：Antel Jochen

  公开号：US20070254863A1

  公开（公告）日：2007-11-01

  Methods of treating one or more medical conditions by administering to a subject in need thereof an effective amount of a CB x modulator having K ATP channel modulating properties are described herein. Also described are methods of using a CB x modulator having K ATP channel modulating properties to treat one or more medical conditions.