1-(4-chloro-phenyl)-2-(2,4-dichloro-phenyl)-5-methanesulfonyl-1H-imidazole-4-carboxylic acid piperidin-1-ylamide | 847474-88-8

• 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-methanesulfonyl-1H-imidazole-4-carboxylic acid piperidin-1-ylamide
• 英文别名: 1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-(methylsulfonyl)-N-piperidin-1-yl-1H-imidazole-4-carboxamide；1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-methylsulfonyl-N-(piperidin-1-yl)-1H-imidazole-4-carboxamide；1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-methylsulfonyl-N-piperidin-1-ylimidazole-4-carboxamide
• CAS: 847474-88-8
• 化学式: C₂₂H₂₁Cl₃N₄O₃S
• 分子量: 527.859
• InChiKey: XHUGETFAQBCPHR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  33
• 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：
  92.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-methylsulfonyl-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 乙腈 为溶剂， 以84%的产率得到1-(4-chloro-phenyl)-2-(2,4-dichloro-phenyl)-5-methanesulfonyl-1H-imidazole-4-carboxylic acid piperidin-1-ylamide
  参考文献：
  名称：

  Probing the cannabinoid CB1/CB2 receptor subtype selectivity limits of 1,2-diarylimidazole-4-carboxamides by fine-tuning their 5-substitution pattern

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2010.03.068

文献信息

• 1 H-imidazole derivatives having CB1 agonistic, CB1 partial agonistic or CB1-antagonistic activity
  申请人：Kruse G. Cornelis

  公开号：US20050054679A1

  公开（公告）日：2005-03-10

  The present invention relates to a group of novel 1H-imidazole derivatives, to methods for the preparation of these compounds, and to pharmaceutical compositions containing one or more of these compounds as an active component. These 1H-imidazole derivatives are potent cannabinoid-CB 1 receptor agonists, partial agonists or antagonists, useful for the treatment of psychiatric and neurological disorders, as well as and other diseases involving cannabinoid neurotransmission. The compounds have the general formula (I) wherein R and R 1 -R 4 have the meanings given in the specification.

  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。
• Tetrasubstituted imidazole derivatives as cannabinoid CB1 receptor modulators with a high CB1/CB2 receptor subtype selectivity
  申请人：Lange H.M. Josephus

  公开号：US20050267161A1

  公开（公告）日：2005-12-01

  The present invention relates to 1,2,4,5-tetrasubstituted imidazole derivatives as selective cannabinoid CB 1 receptor modulators, in particular CB 1 receptor antagonists or inverse agonists having a high CB 1 /CB 2 receptor subtype selectivity, to methods for the preparation of these compounds and to novel intermediates useful for the synthesis of said imidazole derivatives. The invention also relates to the use of a compound disclosed herein for the manufacture of a medicament giving a beneficial effect. A beneficial effect is disclosed herein or apparent to a person skilled in the art from the specification and general knowledge in the art. The invention also relates to the use of a compound of the invention for the manufacture of a medicament for treating or preventing a disease or condition. More particularly, the invention relates to a new use for the treatment of a disease or condition disclosed herein or apparent to a person skilled in the art from the specification and general knowledge in the art. In embodiments of the invention specific compounds disclosed herein are used for the manufacture of a medicament useful in the treatment of psychiatric and neurological disorders. The compounds have the general formula (I) wherein the symbols have the meanings given in the specification.

  本发明涉及1,2,4,5-四取代咪唑衍生物作为选择性大麻素CB1受体调节剂，特别是具有高CB1/CB2受体亚型选择性的CB1受体拮抗剂或反向激动剂，以及制备这些化合物的方法和用于合成所述咪唑衍生物的新型中间体。本发明还涉及使用本文所述的化合物制备具有有益效果的药物。本文披露或在本领域的规范和一般知识中，对于一个熟练的技术人员来说，有益效果是显而易见的。本发明还涉及使用本发明的化合物制备用于治疗或预防疾病或病症的药物。更具体地，本发明涉及用于治疗本文所披露或在本领域的规范和一般知识中显而易见的疾病或病症的新用途。在本发明的实施例中，具体披露的化合物用于制备用于治疗精神和神经疾病的药物。这些化合物具有通式(I)，其中符号具有规范中给出的含义。
• Tetrasubstituted imidazole derivatives as cannabinoid CB1 receptor modulators with a high CB1/CB2 receptor subtype selectivity
  申请人：Solvay Pharmaceuticals, B.V.

  公开号：US07524867B2

  公开（公告）日：2009-04-28

  The present invention relates to 1,2,4,5-tetrasubstituted imidazole derivatives as selective cannabinoid CB1 receptor modulators, in particular CB1 receptor antagonists or inverse agonists having a high CB1/CB2 receptor subtype selectivity, to methods for the preparation of these compounds and to novel intermediates useful for the synthesis of said imidazole derivatives. The invention also relates to the use of a compound disclosed herein for the manufacture of a medicament giving a beneficial effect. A beneficial effect is disclosed herein or apparent to a person skilled in the art from the specification and general knowledge in the art. The invention also relates to the use of a compound of the invention for the manufacture of a medicament for treating or preventing a disease or condition. More particularly, the invention relates to a new use for the treatment of a disease or condition disclosed herein or apparent to a person skilled in the art from the specification and general knowledge in the art. In embodiments of the invention specific compounds disclosed herein are used for the manufacture of a medicament useful in the treatment of psychiatric and neurological disorders. The compounds have the general formula (I) wherein the symbols have the meanings given in the specification.

  本发明涉及1,2,4,5-四取代咪唑衍生物作为选择性大麻素CB1受体调节剂，特别是具有高CB1/CB2受体亚型选择性的CB1受体拮抗剂或反向激动剂，以及用于制备这些化合物的方法和用于合成所述咪唑衍生物的新型中间体。本发明还涉及使用本文所披露的化合物制造具有有益效果的药物。有益效果在本文或根据本文所披露的技术规范和一般技术知识对熟练技术人员是明显的。本发明还涉及使用本发明的化合物制造用于治疗或预防疾病或症状的药物。更具体地，本发明涉及用于治疗本文所披露的疾病或症状或根据本文所披露的技术规范和一般技术知识对熟练技术人员是明显的疾病或症状的新用途。在本发明实施例中，特定的化合物用于制造用于治疗精神和神经疾病的药物。这些化合物具有通式（I），其中符号具有规范中所给出的含义。
• 1H-imidazole derivatives having CB1 agonistic, CB1 partial agonistic or CB1-antagonistic activity
  申请人：Solvay Pharmaceuticals B.V.

  公开号：US07109216B2

  公开（公告）日：2006-09-19

  The present invention relates to a group of novel 1H-imidazole derivatives, to methods for the preparation of these compounds, and to pharmaceutical compositions containing one or more of these compounds as an active component. These 1H-imidazole derivatives are potent cannabinoid-CB1 receptor agonists, partial agonists or antagonists, useful for the treatment of psychiatric and neurological disorders, as well as and other diseases involving cannabinoid neurotransmission. The compounds have the general formula (I) wherein R and R1–R4 have the meanings given in the specification.

  本发明涉及一组新型1H-咪唑衍生物，涉及制备这些化合物的方法，以及含有其中一种或多种化合物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，可用于治疗精神和神经系统疾病，以及其他涉及大麻素神经递质的疾病。这些化合物具有一般式（I），其中R和R1-R4在规范中给出的含义。
• 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。