N-(azepan-1-yl)-1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-(methylthio)-1H-imidazole-4-carboxamide | 871314-89-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-(azepan-1-yl)-1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-(methylthio)-1H-imidazole-4-carboxamide
• 英文别名: N-(azepan-1-yl)-1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-methylsulfanylimidazole-4-carboxamide
• CAS: 871314-89-5
• 化学式: C₂₃H₂₃Cl₃N₄OS
• 分子量: 509.887
• InChiKey: NHUPNEJSRIUIAU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  75.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-methylsulfanyl-1H-imidazole-4-carboxylic acid 、 1-氨基高哌啶 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， 反应 16.0h， 以73%的产率得到N-(azepan-1-yl)-1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-(methylthio)-1H-imidazole-4-carboxamide
  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

• 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：EP1756066B1

  公开（公告）日：2008-08-20
• US7524867B2
  申请人：——

  公开号：US7524867B2

  公开（公告）日：2009-04-28
• 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.