1-{[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]carbonyl}-4-phenylpiperidine-4-carboxamide | 1365037-07-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-{[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]carbonyl}-4-phenylpiperidine-4-carboxamide
• 英文别名: 1-[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carbonyl]-4-phenylpiperidine-4-carboxamide
• CAS: 1365037-07-5
• 化学式: C₂₉H₂₅Cl₃N₄O₂
• 分子量: 567.902
• InChiKey: HCRHKHNIDPJLBQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  38
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  81.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-(2,4-二氯苯基)-5-对氯苯基-4-甲基-吡唑-3-甲酸 在 草酰氯 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 氯化铵 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 90.0h， 生成 1-{[5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazol-3-yl]carbonyl}-4-phenylpiperidine-4-carboxamide
  参考文献：
  名称：

  Design and Synthesis of Cannabinoid Receptor 1 Antagonists for Peripheral Selectivity

  摘要：

  Antagonists of cannabinoid receptor 1 (CB1) have potential for the treatment of several diseases such as obesity, liver disease, and diabetes. Recently, development of several CB1 antagonists was halted because of adverse central nervous system (CNS) related side effects observed with rimonabant, the first clinically approved CB1 inverse agonist. However, recent studies indicate that regulation of peripherally expressed CB1 with CNS-sparing compounds is a viable strategy to treat several important disorders. Our efforts aimed at rationally designing peripherally restricted CB1 antagonists have resulted in compounds that have limited blood-brain barrier (BBB) permeability and CNS exposure in preclinical in vitro and in vivo models. Typically, compounds with high topological polar surface areas (TPSAs) do not cross the BBB passively. Compounds with TPSAs higher than that for rimonabant (rimonabant TPSA = 50) and excellent functional activity with limited CNS penetration were identified. These compounds will serve as templates for further optimization.

  DOI：

  10.1021/jm201731z

文献信息

• [EN] PYRAZOLE DERIVATIVES AS CANNABINOID RECEPTOR 1 ANTAGONISTS<br/>[FR] DÉRIVÉS DE PYRAZOLE UTILISÉS EN TANT QU'ANTAGONISTES DU RÉCEPTEUR DE TYPE 1 DES CANNABINOÏDES
  申请人：RES TRIANGLE INST

  公开号：WO2012174362A1

  公开（公告）日：2012-12-20

  The invention provides compounds capable of acting as antagonists at cannabanoid receptors according to the following formula: Such compounds may be used to treat conditions for which the cannabinoid receptor system has been implicated, such as obesity, liver disease, diabetes, pain, and inflammation.

  该发明提供了一种能够作为大麻素受体拮抗剂的化合物，其化学式如下：这些化合物可用于治疗与大麻素受体系统有关的疾病，如肥胖、肝病、糖尿病、疼痛和炎症。
• PYRAZOLE DERIVATIVES AS CANNABINOID RECEPTOR 1 ANTAGONISTS
  申请人：Fulp Alan Bradley

  公开号：US20140107157A1

  公开（公告）日：2014-04-17

  The invention provides compounds capable of acting as antagonists at cannabanoid receptors according to the following formula: Such compounds may be used to treat conditions for which the cannabinoid receptor system has been implicated, such as obesity, liver disease, diabetes, pain, and inflammation.

  本发明提供了一种能够作为大麻素受体拮抗剂的化合物，其化学式如下：这些化合物可用于治疗与大麻素受体系统有关的疾病，如肥胖症、肝脏疾病、糖尿病、疼痛和炎症等。
• Pyrazole derivatives as cannabinoid receptor 1 antagonists
  申请人：Fulp Alan Bradley

  公开号：US09133128B2

  公开（公告）日：2015-09-15

  The invention provides compounds capable of acting as antagonists at cannabanoid receptors according to the following formula: Such compounds may be used to treat conditions for which the cannabinoid receptor system has been implicated, such as obesity, liver disease, diabetes, pain, and inflammation.

  该发明提供了一些化合物，其能够作为大麻素受体的拮抗剂，化合物的化学式如下：这些化合物可以用于治疗与大麻素受体系统有关的疾病，例如肥胖症、肝病、糖尿病、疼痛和炎症。
• US9133128B2
  申请人：——

  公开号：US9133128B2

  公开（公告）日：2015-09-15
• Design and Synthesis of Cannabinoid Receptor 1 Antagonists for Peripheral Selectivity
  作者：Alan Fulp、Katherine Bortoff、Herbert Seltzman、Yanan Zhang、James Mathews、Rodney Snyder、Tim Fennell、Rangan Maitra

  DOI：10.1021/jm201731z

  日期：2012.3.22

  Antagonists of cannabinoid receptor 1 (CB1) have potential for the treatment of several diseases such as obesity, liver disease, and diabetes. Recently, development of several CB1 antagonists was halted because of adverse central nervous system (CNS) related side effects observed with rimonabant, the first clinically approved CB1 inverse agonist. However, recent studies indicate that regulation of peripherally expressed CB1 with CNS-sparing compounds is a viable strategy to treat several important disorders. Our efforts aimed at rationally designing peripherally restricted CB1 antagonists have resulted in compounds that have limited blood-brain barrier (BBB) permeability and CNS exposure in preclinical in vitro and in vivo models. Typically, compounds with high topological polar surface areas (TPSAs) do not cross the BBB passively. Compounds with TPSAs higher than that for rimonabant (rimonabant TPSA = 50) and excellent functional activity with limited CNS penetration were identified. These compounds will serve as templates for further optimization.