1-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-N-(piperidin-1-yl)-1H-1,2,4-triazole-3-carboxamide

• 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-chlorophenyl)-5-(2,4-dichlorophenyl)-N-(piperidin-1-yl)-1H-1,2,4-triazole-3-carboxamide
• 英文别名: 1-(4-chloro-phenyl)-5-(2,4-dichloro-phenyl)-1H-[1,2,4]triazole-3-carboxylic acid piperidin-1-yl-amide；1-(4-chloro-phenyl)-5-(2,4-dichloro-phenyl)-1H-[1,2,4]triazole-3-carboxylic acid piperidin-1-ylamide；1-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-N-piperidin-1-yl-1H-1,2,4-triazole-3-carboxamide；1-(4-Chloro-phenyl)-5-(2,4-dichloro-phenyl)-1H-[1,2,4]triazole-3-carboxylic acid piperidin-1-ylamide; dihydrochloride；1-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-N-piperidin-1-yl-1,2,4-triazole-3-carboxamide
• 化学式: C₂₀H₁₈Cl₃N₅O
• 分子量: 450.755
• InChiKey: COXVLBFQMLJUHG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  63
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2,4-二氯苯甲酰氯 在 盐酸 、 氢氧化钾 、 sodium methylate 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 溶剂黄146 、 三乙胺 、 N,N-二异丙基乙胺 、 sodium nitrite 作用下， 以 甲醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 52.5h， 生成 1-(4-chlorophenyl)-5-(2,4-dichlorophenyl)-N-(piperidin-1-yl)-1H-1,2,4-triazole-3-carboxamide
  参考文献：
  名称：

  利莫那班吡唑部分的生物立体置换：噻唑，三唑和咪唑作为有效和选择性的CB1大麻素受体拮抗剂的合成，生物学性质和分子模型研究。

  摘要：

  基于有效的CB（1）受体拮抗剂利莫那班（SR141716A，1）中存在的1,5-二芳基吡唑基序，将噻唑，三唑和咪唑系列设计为生物等排体。合成了许多目标化合物，并在大麻素（hCB（1）和hCB（2））受体分析中进行了评估。噻唑，三唑和咪唑具有体外（）（）CB（1）拮抗活性，通常表现出相当大的CB（1）与CB（2）受体亚型选择性，从而证明是原始的二芳基吡唑类的大麻素生物等排体。咪唑系列的一些主要代表在CB激动剂诱导的低血压模型和CB激动剂诱导的低体温模型中均显示出口服给药后体内的有效药理活性。分子模型研究表明，关键化合物62和利莫那班之间存在紧密的三维结构重叠。结构-活性关系（SAR）研究表明，咪唑和吡唑系列的生物学结果之间存在密切的相关性。

  DOI：

  10.1021/jm040843r

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。
• PHARMACEUTICAL COMPOSITIONS COMPRISING CB1 CANNABINOID RECEPTOR ANTAGONISTS AND POTASSIUM CHANNEL OPENERS FOR THE TREATMENT OF DIABETES MELLITUS TYPE I, OBESITY AND RELATED CONDITIONS
  申请人：Solvay Pharmaceuticals GmbH

  公开号：EP1807063A2

  公开（公告）日：2007-07-18
• 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.