2,2,2-trifluoro-N-[(4-hydroxyphenyl)methyl]acetamide | 864263-20-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 2,2,2-trifluoro-N-[(4-hydroxyphenyl)methyl]acetamide
• 英文别名: Acetamide, 2,2,2-trifluoro-N-[(4-hydroxyphenyl)methyl]-
• CAS: 864263-20-7
• 化学式: C₉H₈F₃NO₂
• 分子量: 219.163
• InChiKey: NSWUPRIBGLQXGW-UHFFFAOYSA-N

物化性质

• 沸点：
  350.8±42.0 °C(Predicted)
• 密度：
  1.373±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,2,2-trifluoro-N-[(4-hydroxyphenyl)methyl]acetamide 在 吡啶 、 草酰氯 、 potassium carbonate 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 7.0h， 生成 N-(4-amino-2-methylquinolin-6-yl)-2-[4-((trifluoroacetylamino)methyl)phenoxymethyl]benzamide
  参考文献：
  名称：

  Synthesis and pharmacological evaluation of bivalent antagonists of the nociceptin opioid receptor

  摘要：

  Bivalent ligands constituted by two identical pharmacophores structurally related to the Nociceptin Opioid Receptor (NOPr) antagonist JTC-801 were synthesized and their binding affinities for NOPr were evaluated. The novel ligands are formed by two modified JTC-801 units linked by di-iminic and di-aminic spacers with length ranging from three to ten methylene units. Moreover, the synthesis and the pharmacological characterization were extended to the corresponding univalent ligands. The latter compounds consisted in a single modified JTC-801 unit and an alkyl or alkylamino or alkylimino tail. The purpose of this study is to feature the location and surroundings of the allosteric binding site(s) of pharmacophores containing the 4-aminoquinoline structure. Most important, the bivalent ligands were exploited to reveal the eventual occurrence of a supramolecular receptorial architecture of the NOPr.All the bivalent derivatives 4 and 5 proved to be active in the nanomolar range with no outstanding dependence on the chain length. They showed potencies from three to ten times higher than the corresponding monomers. Consequently, results clearly indicated a positive role of the second pharmacophore in the ligand-protein interaction. The pharmacological profile of I he monomers 7 and 8 clarified the contribution of the linker chain to NOP receptor affinity and suggested the presence of a lipophilic acidic site neighbouring the binding site of the JTC-like ligands.Selectivity of saturated compounds 5, 7, and 8 was tested by binding experiments on delta, kappa and mu opioid receptors. Results indicated a general loss of selectivity as compared to JTC-801. In the [(35)S]GTP gamma S binding assay, all the compounds revealed antagonistic properties at the NOP Receptor.In conclusion the present study set the basis for a systematic investigation on the structural modifications that can be introduced into novel ligands for NOPr and helped to feature the surrounds of the allosteric site of NOPr. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.01.040
• 作为产物：
  描述：

  2,2,2-trifluoro-N-(4-methoxybenzyl)acetamide 、 三溴化硼 在 氮气 、 ice 、 碳酸氢钠 、 氯仿 、 Sodium sulfate-III 作用下， 以 二氯甲烷 为溶剂， 反应 16.33h， 以to obtain the desired intermediate (8.8 g, 40 mmol)的产率得到2,2,2-trifluoro-N-[(4-hydroxyphenyl)methyl]acetamide
  参考文献：
  名称：

  6 Substituted 2, 3,4,5 Tetrahydro-1H-Benzo[d]Azepines as 5-HT2c Receptor Agonist

  摘要：

  本发明提供了公式I的6-取代的2,3,4,5-四氢-1H-苯并[d]氮杂环作为选择性5-HT2C受体激动剂，用于治疗5-HT2C相关疾病，包括肥胖症、强迫症、抑郁症和焦虑症：其中：R6为—S—R14；其他取代基如规范中所定义。

  公开号：

  US20120028961A1

文献信息

• [EN] 6-SUBSTITUTED 2,3,4,5-TETRAHYDRO-1H-BENZO[D]AZEPINES AS 5-HT2C RECEPTOR AGONISTS<br/>[FR] 2,3,4,5-TETRAHYDRO-1H-BENZO[D]AZEPINES SUBSTITUES EN POSITION 6 EN TANT QU'AGONISTES DE RECEPTEUR 5-HT2C
  申请人：LILLY CO ELI

  公开号：WO2005082859A1

  公开（公告）日：2005-09-09

  The present invention provides 6-substituted 2,3,4,5-tetrahydro-1H-benzo[d]azepines of Formula I as selective 5-HT2C receptor agonists for the treatment of 5-HT2C associated disorders including obesity, obsessive/compulsive disorder, depression, and anxiety: I where: R6 is -C=C-R10, -O-R12, -S-R14, or -NR24R25; and other substituents are as defined in the specification.

  本发明提供了公式I中的6-取代的2,3,4,5-四氢-1H-苯并[d]氮杂环庚烯作为选择性5-HT2C受体激动剂，用于治疗与5-HT2C相关的疾病，包括肥胖症、强迫症/强迫性障碍、抑郁症和焦虑症：I其中：R6为-C=C-R10，-O-R12，-S-R14或-NR24R25；其他取代基如规范中所定义。
• 6-SUBSTITUTED 2,3,4,5-TETRAHYDRO-1H-BENZO[D]AZEPINES AS 5-HT2C RECEPTOR AGONISTS
  申请人：Allen John Gordon

  公开号：US20090099155A1

  公开（公告）日：2009-04-16

  The present invention provides 6-substituted 2,3,4,5-tetrahydro-1H-benzoazepines of Formula I as selective 5-HT 2C receptor agonists for the treatment of 5-HT 2C associated disorders including obesity, obsessive/compulsive disorder, depression, and anxiety: where: R 6 is -C≡C-R 10 , -O-R 12 , -S-R 14 , or -NR 24 R 25 ; and other substituents are as defined in the specification.

  本发明提供了式I的6-取代的2,3,4,5-四氢-1H-苯并氮烯作为选择性5-HT2C受体激动剂，用于治疗5-HT2C相关疾病，包括肥胖症、强迫症、抑郁症和焦虑症：其中：R6为-C≡C-R10，-O-R12，-S-R14或-NR24R25；其他取代基如规范中所定义。
• 6 Substituted 2, 3,4,5 Tetrahydro-1H-Benzo[d]Azepines as 5-HT2c Receptor Agonist
  申请人：ALLEN JOHN GORDON

  公开号：US20120028961A1

  公开（公告）日：2012-02-02

  The present invention provides 6-substituted 2,3,4,5-tetrahydro-1H-benzo[d]azepines of Formula I as selective 5-HT 2C receptor agonists for the treatment of 5-HT 2C associated disorders including obesity, obsessive/compulsive disorder, depression, and anxiety: where: R 6 is —S—R 14 ; and other substituents are as defined in the specification.

  本发明提供了公式I的6-取代的2,3,4,5-四氢-1H-苯并[d]氮杂环作为选择性5-HT2C受体激动剂，用于治疗5-HT2C相关疾病，包括肥胖症、强迫症、抑郁症和焦虑症：其中：R6为—S—R14；其他取代基如规范中所定义。
• 6-substituted 2,3,4,5-tetrahydro-1H-benzo[d]azepines as 5-HT2C receptor agonists
  申请人：Eli Lilly and Company

  公开号：US08022062B2

  公开（公告）日：2011-09-20

  The present invention provides 6-substituted 2,3,4,5-tetrahydro-1H-benzo[d]azepines of Formula I as selective 5-HT2C receptor agonists for the treatment of 5-HT2C associated disorders including obesity, obsessive/compulsive disorder, depression, and anxiety: where: R6 is —C≡C—R10, —O—R12, —S—R14, or —NR24R25; and other substituents are as defined in the specification.

  本发明提供了式I的6-取代2,3,4,5-四氢-1H-苯并[d]氮杂环化合物，作为选择性5-HT2C受体激动剂，用于治疗与5-HT2C相关的疾病，包括肥胖症、强迫症、抑郁症和焦虑症：其中：R6是—C≡C—R10，—O—R12，—S—R14或—NR24R25; 其他取代基如规范中定义。
• 6-Substituted 2,3,4,5-Tetrahydro-1H-Benzo [d]Azepines as 5-HT2C Receptor Agonists
  申请人：ELI LILLY AND COMPANY

  公开号：EP2479168A1

  公开（公告）日：2012-07-25

  The present invention provides 6-substituted 2,3,4,5-tetrahydro-1H-benzo[d]azepines of Formula I as selective 5-HT2C receptor agonists for the treatment of 5-HT2C associated disorders including obesity, obsessive/compulsive disorder, depression, and anxiety: where: R6 is -S-L-R15 and other substituents are as defined in the specification.

  本发明提供了式 I 的 6-取代 2,3,4,5-四氢-1H-苯并[d]氮杂卓作为选择性 5-HT2C 受体激动剂，用于治疗与 5-HT2C 相关的疾病，包括肥胖症、强迫症、抑郁症和焦虑症： 其中 R6 是-S-L-R15 和其他取代基如说明书中所定义。