6-chloro-1-(2’,4’-dichlorophenyl)-N-piperidin-1-yl-1,4-di-hydroindeno[1,2-c]pyrazole-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: 6-chloro-1-(2’,4’-dichlorophenyl)-N-piperidin-1-yl-1,4-di-hydroindeno[1,2-c]pyrazole-3-carboxamide
• 英文别名: 6-chloro-1-(2,4-dichlorophenyl)-N-piperidin-1-yl-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamide；1,4-Dihydroindeno[1,2-c]-pyrazole；6-chloro-1-(2,4-dichlorophenyl)-N-piperidin-1-yl-4H-indeno[1,2-c]pyrazole-3-carboxamide
• 化学式: C₂₂H₁₉Cl₃N₄O
• 分子量: 461.778
• InChiKey: AOONPZHOPMGIMM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  50.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2,4-二氯苯肼盐酸盐 在 氢氧化钾 、 氯化亚砜 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 8.0h， 生成 6-chloro-1-(2’,4’-dichlorophenyl)-N-piperidin-1-yl-1,4-di-hydroindeno[1,2-c]pyrazole-3-carboxamide
  参考文献：
  名称：

  Tricyclic Pyrazoles. Part 1: Synthesis and Biological Evaluation of Novel 1,4-Dihydroindeno[1,2-c]pyrazol-based Ligands for CB1and CB2 Cannabinoid Receptors

  摘要：

  Cannabinoids receptors, cellular elements of the endocannabinoid system, have been the focus of extensive studies because of their potential functional role in several important physiological and pathological processes. To further evaluate the properties of CB receptors, especially CB1 and CB2 subtypes, we have designed, using SR141716A as a benchmark, a new series of rigid 1-aryl-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamides. Compounds I were synthesized from substituted 1-aryl-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxylic acids and requisite amines. The various analogues were assayed for binding both to the brain and peripheral cannabinoid receptors (CB1 and CB2). Seven of the new compounds displayed very high in vitro CB2 binding affinities, especially 1a, 1b, 1c, 1e, 1g, 1h and 1j which showed K-i values of 0.34, 0.225, 0.27, 0.23, 0.385, 0.037 and 0.9 nM, respectively. Compounds 1a, 1b, 1c and 1h showed the highest selectivity for CB2 receptor with K-i(CB1) to K-i(CB2) ratios of 6029, 5635, 5814 and 9810, respectively. Noticeably, 1h exhibited the highest affinity and selectivity for CB2 receptors. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00319-x

文献信息

• Methods and Compositions for Reducing Serum Levels of Immunoglobulin E (IGE)
  申请人：UNIVERSITY OF SOUTH FLORIDA

  公开号：US20140350052A1

  公开（公告）日：2014-11-27

  The present disclosure provides methods and pharmaceutical compositions for reducing the serum level of immunoglobulin IgE in an animal or human subject. It has been found that reducing or inhibiting the activity of the cannabinoid receptor CB2 leads to an increase in IgE in serum levels. Conversely, activation of the CB2 receptor by an agonist results in a reduction in IgE serum levels. The compositions and methods of the disclosure, therefore, provide a means to reduce or eliminate symptoms of immune system-related conditions resulting from IgE generation, such as an allergy, hay fever, and the like.
• US9289421B2
  申请人：——

  公开号：US9289421B2

  公开（公告）日：2016-03-22
• [EN] METHODS AND COMPOSITIONS FOR REDUCING SERUM LEVELS OF IMMUNOGLOBULIN E (IGE)<br/>[FR] MÉTHODES ET COMPOSITIONS VISANT À DIMINUER LES TAUX SÉRIQUES D'IMMUNOGLOBULINE E (IGE)
  申请人：UNIV SOUTH FLORIA

  公开号：WO2013033155A1

  公开（公告）日：2013-03-07

  The present disclosure provides methods and pharmaceutical compositions for reducing the serum level of immunoglobulin IgE in an animal or human subject. It has been found that reducing or inhibiting the activity of the cannabinoid receptor CB2 leads to an increase in IgE in serum levels. Conversely, activation of the CB2 receptor by an agonist results in a reduction in IgE serum levels. The compositions and methods of the disclosure, therefore, provide a means to reduce or eliminate symptoms of immune system-related conditions resulting from IgE generation, such as an allergy, hay fever, and the like.
• Tricyclic Pyrazoles. Part 1: Synthesis and Biological Evaluation of Novel 1,4-Dihydroindeno[1,2-c]pyrazol-based Ligands for CB1and CB2 Cannabinoid Receptors
  作者：Jean-Mario Mussinu、Stefania Ruiu、Antonio C Mulè、Amedeo Pau、Mauro A.M Carai、Giovanni Loriga、Gabriele Murineddu、Gérard A Pinna

  DOI：10.1016/s0968-0896(02)00319-x

  日期：2003.1

  Cannabinoids receptors, cellular elements of the endocannabinoid system, have been the focus of extensive studies because of their potential functional role in several important physiological and pathological processes. To further evaluate the properties of CB receptors, especially CB1 and CB2 subtypes, we have designed, using SR141716A as a benchmark, a new series of rigid 1-aryl-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxamides. Compounds I were synthesized from substituted 1-aryl-1,4-dihydroindeno[1,2-c]pyrazole-3-carboxylic acids and requisite amines. The various analogues were assayed for binding both to the brain and peripheral cannabinoid receptors (CB1 and CB2). Seven of the new compounds displayed very high in vitro CB2 binding affinities, especially 1a, 1b, 1c, 1e, 1g, 1h and 1j which showed K-i values of 0.34, 0.225, 0.27, 0.23, 0.385, 0.037 and 0.9 nM, respectively. Compounds 1a, 1b, 1c and 1h showed the highest selectivity for CB2 receptor with K-i(CB1) to K-i(CB2) ratios of 6029, 5635, 5814 and 9810, respectively. Noticeably, 1h exhibited the highest affinity and selectivity for CB2 receptors. (C) 2002 Elsevier Science Ltd. All rights reserved.