2-{1-(2-chlorophenyl)-5-(4-chlorophenyl)-3-[4-(4-fluorophenyl)-4-hydroxypiperidine-1-carbonyl]-1H-pyrazol-4-yl}acetamidine | 1027617-45-3

• 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: 2-{1-(2-chlorophenyl)-5-(4-chlorophenyl)-3-[4-(4-fluorophenyl)-4-hydroxypiperidine-1-carbonyl]-1H-pyrazol-4-yl}acetamidine
• 英文别名: 2-(1-(2-chlorophenyl)-5-(4-chlorophenyl)-3-(4-(4-fluorophenyl)-4-hydroxypiperidine-1-carbonyl)-1H-pyrazol-4-yl)acetimidamide；2-[1-(2-chlorophenyl)-5-(4-chlorophenyl)-3-[4-(4-fluorophenyl)-4-hydroxypiperidine-1-carbonyl]pyrazol-4-yl]ethanimidamide
• CAS: 1027617-45-3
• 化学式: C₂₉H₂₆Cl₂FN₅O₂
• 分子量: 566.462
• InChiKey: PYMDSMHRMYDTDG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  39
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-(1-(2-chlorophenyl)-5-(4-chlorophenyl)-3-(4-(4-fluorophenyl)-4-hydroxypiperidine-1-carbonyl)-1H-pyrazol-4-yl)acetonitrile 在 三甲基铝 、 氯化铵 作用下， 以 甲苯 为溶剂， 生成 2-{1-(2-chlorophenyl)-5-(4-chlorophenyl)-3-[4-(4-fluorophenyl)-4-hydroxypiperidine-1-carbonyl]-1H-pyrazol-4-yl}acetamidine
  参考文献：
  名称：

  Conversion of 4-cyanomethyl-pyrazole-3-carboxamides into CB1 antagonists with lowered propensity to pass the blood–brain-barrier

  摘要：

  A series of amides, amidines and amidoximes have been made from the corresponding nitrile compounds, to provide potent antagonists and inverse agonists for the CB1 receptor with considerably lower lipophiliciy, higher polar surface area and improved plasma/brain ratios compared to the centrally acting rimonabant. Extensive investigations of ADME and in vivo pharmacological properties led to selection of the amide series and specifically the 4-(4-fluorophenyl)piperidin-4-ol derivative D4. A clear improvement in the peripheral pro. le over rimonabant was seen, although some contribution of central effect on the pronounced weight reduction in obese mice cannot be ruled out. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.12.003

文献信息

• Conversion of 4-cyanomethyl-pyrazole-3-carboxamides into CB1 antagonists with lowered propensity to pass the blood–brain-barrier
  作者：Jean-Marie Receveur、Anthony Murray、Jean-Michel Linget、Pia K. Nørregaard、Martin Cooper、Emelie Bjurling、Peter Aadal Nielsen、Thomas Högberg

  DOI：10.1016/j.bmcl.2009.12.003

  日期：2010.1

  A series of amides, amidines and amidoximes have been made from the corresponding nitrile compounds, to provide potent antagonists and inverse agonists for the CB1 receptor with considerably lower lipophiliciy, higher polar surface area and improved plasma/brain ratios compared to the centrally acting rimonabant. Extensive investigations of ADME and in vivo pharmacological properties led to selection of the amide series and specifically the 4-(4-fluorophenyl)piperidin-4-ol derivative D4. A clear improvement in the peripheral pro. le over rimonabant was seen, although some contribution of central effect on the pronounced weight reduction in obese mice cannot be ruled out. (C) 2009 Elsevier Ltd. All rights reserved.