4-trifluoroacetamide-propofol

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-trifluoroacetamide-propofol
• 英文别名: N-(3,5-Diisopropyl-4-hydroxyphenyl)-2,2,2-trifluoroacetamide；2,2,2-trifluoro-N-[4-hydroxy-3,5-di(propan-2-yl)phenyl]acetamide
• 化学式: C₁₄H₁₈F₃NO₂
• 分子量: 289.298
• InChiKey: BTLZUTLQKYIVRA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  丙泊酚 在 吡啶 、 盐酸 、 sodium hydroxide 、 tin 、 硫酸 、 硝酸 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 4-trifluoroacetamide-propofol
  参考文献：
  名称：

  Propofol Analogues. Synthesis, Relationships between Structure and Affinity at GABA_A Receptor in Rat Brain, and Differential Electrophysiological Profile at Recombinant Human GABA_A Receptors

  摘要：

  A number of propofol (2,6-diisopropylphenol) congeners and derivatives were synthesized and their in vitro capability to affect GABA(A) receptors determined by the inhibition of the specific [S-35]-tert-butylbicyclophosphorothionate ([S-35]TBPS) binding to rat whole brain membranes. Introduction of halogen (Cl, Br, and I) and benzoyl substituents in the para position of the phenyl group resulted in ligands with higher potency at inhibiting [S-35]TBPS binding. A quantitative structure-affinity relationship (QSAR) study demonstrated that affinity is enhanced by increases in lipophilicity of the ligand whereas affinity is adversely affected by increases in size of the substituent para to the phenolic hydroxyl group. Consistent with the displacement of [S-35]TBPS and with the activation of GABA(A) receptors, we demonstrate that ligands displaying high affinity (i.e., 2-4, and 8) are able to increase GABA-stimulated chloride currents in oocytes expressing human GABA(A) receptors and to directly activate chloride currents in an electrophysiological assay. Among them, compound 4 showed a rather peculiar profile in the electrophysiological examination with cloned alpha(1) beta(2) gamma(2) GABA(A) receptors. Indeed, compared to propofol, it displayed a much greater efficacy at potentiating GABA-elicited chloride currents, but a much lower efficacy at producing a direct activation of the chloride channel in the absence of GABA. This behavior may give to compound 4 pharmacological properties that are more similar to anxiolytic and anticonvulsant drugs than to those of general anesthetics.

  DOI：

  10.1021/jm970681h

文献信息

• [EN] COMPOUNDS FOR USE IN THE TREATMENT OF PAIN<br/>[FR] COMPOSÉS POUR UTILISATION DANS LE TRAITEMENT DE LA DOULEUR
  申请人：UNIV LIVERPOOL

  公开号：WO2010067069A1

  公开（公告）日：2010-06-17

  The present invention concerns compounds derived from the anaethetic propofol. The compounds may be useful in the treatment of pain, particularly, but not exclusively, chronic pain and central pain sensitisation.

  本发明涉及从麻醉药丙泊酚衍生的化合物。这些化合物可能在治疗疼痛方面有用，尤其是慢性疼痛和中枢疼痛敏化，但不仅限于此。
• COMPOUNDS FOR USE IN THE TREATMENT OF PAIN
  申请人：The University Of Dundee

  公开号：EP2373605B1

  公开（公告）日：2014-08-13
• US8507724B2
  申请人：——

  公开号：US8507724B2

  公开（公告）日：2013-08-13
• Propofol Analogues. Synthesis, Relationships between Structure and Affinity at GABA_A Receptor in Rat Brain, and Differential Electrophysiological Profile at Recombinant Human GABA_A Receptors
  作者：Giuseppe Trapani、Andrea Latrofa、Massimo Franco、Cosimo Altomare、Enrico Sanna、Marcello Usala、Giovanni Biggio、Gaetano Liso

  DOI：10.1021/jm970681h

  日期：1998.5.1

  A number of propofol (2,6-diisopropylphenol) congeners and derivatives were synthesized and their in vitro capability to affect GABA(A) receptors determined by the inhibition of the specific [S-35]-tert-butylbicyclophosphorothionate ([S-35]TBPS) binding to rat whole brain membranes. Introduction of halogen (Cl, Br, and I) and benzoyl substituents in the para position of the phenyl group resulted in ligands with higher potency at inhibiting [S-35]TBPS binding. A quantitative structure-affinity relationship (QSAR) study demonstrated that affinity is enhanced by increases in lipophilicity of the ligand whereas affinity is adversely affected by increases in size of the substituent para to the phenolic hydroxyl group. Consistent with the displacement of [S-35]TBPS and with the activation of GABA(A) receptors, we demonstrate that ligands displaying high affinity (i.e., 2-4, and 8) are able to increase GABA-stimulated chloride currents in oocytes expressing human GABA(A) receptors and to directly activate chloride currents in an electrophysiological assay. Among them, compound 4 showed a rather peculiar profile in the electrophysiological examination with cloned alpha(1) beta(2) gamma(2) GABA(A) receptors. Indeed, compared to propofol, it displayed a much greater efficacy at potentiating GABA-elicited chloride currents, but a much lower efficacy at producing a direct activation of the chloride channel in the absence of GABA. This behavior may give to compound 4 pharmacological properties that are more similar to anxiolytic and anticonvulsant drugs than to those of general anesthetics.