N-[[4-(aminomethyl)cyclohexyl]methyl]-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide | 1338604-32-2

• 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-[[4-(aminomethyl)cyclohexyl]methyl]-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide
• CAS: 1338604-32-2
• 化学式: C₂₅H₂₇Cl₃N₄O
• 分子量: 505.875
• InChiKey: SAZOOZOCEZSXGN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  72.9
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-[[4-(aminomethyl)cyclohexyl]methyl]-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide 在 磺酰胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 16.0h， 生成 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-({4-[(sulfamoylamino)methyl]cyclohexyl}methyl)-1H-pyrazole-3-carboxamide
  参考文献：
  名称：

  Towards rational design of cannabinoid receptor 1 (CB1) antagonists for peripheral selectivity

  摘要：

  CB1 receptor antagonists that are peripherally restricted were targeted. Compounds with permanent charge as well as compounds that have increased polar surface area were made and tested against CB1 for binding and activity. Sulfonamide and sulfamide with high polar surface area and good activity at CB1 were rationally designed and pharmacologically tested. Further optimization of these compounds and testing could lead to the development of a new class of therapeutics to treat disorders where the CB1 receptor system has been implicated. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.08.032
• 作为产物：
  描述：

  1,4-环己烷双(甲基胺) 、 1-(2,4-二氯苯基)-5-对氯苯基-4-甲基-吡唑-3-甲酸 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 作用下， 以 四氢呋喃 为溶剂， 生成 N-[[4-(aminomethyl)cyclohexyl]methyl]-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methylpyrazole-3-carboxamide
  参考文献：
  名称：

  Towards rational design of cannabinoid receptor 1 (CB1) antagonists for peripheral selectivity

  摘要：

  CB1 receptor antagonists that are peripherally restricted were targeted. Compounds with permanent charge as well as compounds that have increased polar surface area were made and tested against CB1 for binding and activity. Sulfonamide and sulfamide with high polar surface area and good activity at CB1 were rationally designed and pharmacologically tested. Further optimization of these compounds and testing could lead to the development of a new class of therapeutics to treat disorders where the CB1 receptor system has been implicated. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.08.032

文献信息

• 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.
• Towards rational design of cannabinoid receptor 1 (CB1) antagonists for peripheral selectivity
  作者：Alan Fulp、Katherine Bortoff、Yanan Zhang、Herbert Seltzman、Rodney Snyder、Rangan Maitra

  DOI：10.1016/j.bmcl.2011.08.032

  日期：2011.10

  CB1 receptor antagonists that are peripherally restricted were targeted. Compounds with permanent charge as well as compounds that have increased polar surface area were made and tested against CB1 for binding and activity. Sulfonamide and sulfamide with high polar surface area and good activity at CB1 were rationally designed and pharmacologically tested. Further optimization of these compounds and testing could lead to the development of a new class of therapeutics to treat disorders where the CB1 receptor system has been implicated. (C) 2011 Elsevier Ltd. All rights reserved.