2-(1-(2-chlorophenyl)-5-(4-chlorophenyl)-3-(4-(4-fluorophenyl)-4-hydroxypiperidine-1-carbonyl)-1H-pyrazol-4-yl)acetonitrile | 1207865-20-0

• 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)acetonitrile
• 英文别名: 2-[1-(2-chlorophenyl)-5-(4-chlorophenyl)-3-[4-(4-fluorophenyl)-4-hydroxypiperidine-1-carbonyl]pyrazol-4-yl]acetonitrile
• CAS: 1207865-20-0
• 化学式: C₂₉H₂₃Cl₂FN₄O₂
• 分子量: 549.432
• InChiKey: KGGOHKJYYUEGMG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 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：
  82.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  4-(4-氟苯基)-哌啶-4-醇盐酸盐 、 5-(4-chlorophenyl)-1-(2-chlorophenyl)-4-cyanomethyl-1H-pyrazole-3-carboxylic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 生成 2-(1-(2-chlorophenyl)-5-(4-chlorophenyl)-3-(4-(4-fluorophenyl)-4-hydroxypiperidine-1-carbonyl)-1H-pyrazol-4-yl)acetonitrile
  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.
• Exploring SAR features in diverse library of 4-cyanomethyl-pyrazole-3-carboxamides suitable for further elaborations as CB1 antagonists
  作者：Martin Cooper、Jean-Marie Receveur、Emelie Bjurling、Pia K. Nørregaard、Peter Aadal Nielsen、Niklas Sköld、Thomas Högberg

  DOI：10.1016/j.bmcl.2009.11.047

  日期：2010.1

  A chemically diverse library of secondary and tertiary 4-cyanomethyl-1,5-diphenyl-1H-pyrazole-3-carboxamides was synthesized to enable mapping of the SAR, in the eastern amide region, with regard to CB1 antagonist activity, This study was initiated as a prelude to the design and synthesis of possible CB1 antagonists that do not readily pass the blood-brain-barrier. In general a range of modi. cations were found to be tolerated in this part of the molecule, although polar and especially charged groups did to a degree reduce the CB1 antagonistic activity. Several compounds with single-digit or even sub-nanomolar potency, suitable for further elaboration of the nitrile moiety, were identified. (C) 2009 Elsevier Ltd. All rights reserved.