(+/-)-N-[2-(2,5-dimethoxyphenyl)-1-methylethyl]-2,2,2-trifluoroacetamide | 79315-43-8

• 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: (+/-)-N-[2-(2,5-dimethoxyphenyl)-1-methylethyl]-2,2,2-trifluoroacetamide
• 英文别名: N-(trifluoroacetyl)-1-(2,5-dimethoxyphenyl)-2-aminopropane；N-[1-(2,5-dimethoxyphenyl)propan-2-yl]-2,2,2-trifluoroacetamide
• CAS: 79315-43-8
• 化学式: C₁₃H₁₆F₃NO₃
• 分子量: 291.27
• InChiKey: CKEYUNCNEBUQDJ-UHFFFAOYSA-N

物化性质

• 沸点：
  378.4±42.0 °C(Predicted)
• 密度：
  1.201±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (+/-)-N-[2-(2,5-dimethoxyphenyl)-1-methylethyl]-2,2,2-trifluoroacetamide 在 sodium hydroxide 作用下， 反应 14.0h， 生成 4-(2-氯乙基)-1,2-二甲氧基苯
  参考文献：
  名称：

  [125I] -1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷：一种碘标记的放射性配体，专门标记了5-HT2 5-羟色胺受体的激动剂高亲和力状态。

  摘要：

  DOI：

  10.1021/jm00396a003
• 作为产物：
  描述：

  2-氨基-4-苯基丙烷盐酸盐 、 三氟乙酸酐 反应 2.0h， 以74%的产率得到(+/-)-N-[2-(2,5-dimethoxyphenyl)-1-methylethyl]-2,2,2-trifluoroacetamide
  参考文献：
  名称：

  A structure-affinity study of the binding of 4-substituted analogs of 1-(2,5-dimethoxyphenyl)-2-aminopropane at 5-HT2 serotonin receptors

  摘要：

  With [3H]ketanserin as the radioligand, structure-affinity relationships (SAFIRs) for binding at central 5-HT2 serotonin receptors (rat frontal cortex) were examined for a series of 27 4-substituted 1-(2,5-dimethoxyphenyl)-2-aminopropane derivatives (2,5-DMAs). The affinity (Ki values) ranged over a span of several orders of magnitude. It appears that the lipophilic character of the 4-position substituent plays a major role in determining the affinity of these agents for 5-HT2 receptors, 2,5-DMAs with polar 4-substituents (e.g. OH, NH2, COOH) display a very low affinity (Ki greater than 25,000 nM) for these receptors, whereas those with lipophilic functions display a significantly higher affinity. The results of these studies prompted us to synthesize and evaluate examples of newer lipophilic derivatives and several of these (e.g. n-hexyl, n-octyl) bind with very high (Ki values = 2.5 and 3 nM, respectively) affinities at central 5-HT2 sites. Although, 2,5-DMAs are generally considered to be 5-HT2 agonists, preliminary studies with isolated rat thoracic aorta suggest that some of the more lipophilic derivatives (e.g. the n-hexyl and n-octyl derivatives) are 5-HT2 antagonists.

  DOI：

  10.1021/jm00165a023

文献信息

• 1-[4-(3-Phenylalkyl)phenyl]-2-aminopropanes as 5-HT_2A Partial Agonists
  作者：Cynthia S. Dowd、Katharine Herrick-Davis、Christina Egan、Ann DuPre、Carol Smith、Milt Teitler、Richard A. Glennon

  DOI：10.1021/jm9906062

  日期：2000.8.1

  Phenylalkylamines such as 1-(4-bromo-2,5-dimethoxyphenyl)-2-aminopropane (DOB; Pa) and its corresponding iodo derivative DOI (2) are commonly used 5-HT2 serotonin agonists. Previous studies have established that the 2,5-dimethoxy substitution pattern found in these compounds is optimal for high affinity at 5-HT2A receptors and that substituents at the 4-position can modulate affinity over a wide range. We have previously shown, however, that when the 4-position is substituted with a 3-phenylpropyl substituent (i.e., 3), the compound binds with an affinity comparable to that of Pa but that it possesses 5-HT2A antagonist character. The present study examined the structure-affinity relationships of 3, and the results were very much unexpected. That is, the 2,5-dimethoxy substitution pattern of 3 is not required for high affinity. Either of the two methoxy groups can be removed without untoward effect on affinity, and relocation of the methoxy substituents actually enhances affinity by as much as an order of magnitude. None of the compounds displayed more than 20-fold selectivity for 5-HT2A over 5-HT2C receptors. In addition, several were demonstrated to act as 5-HT2A partial agonists. As such, the results of this study suggest that the structure-affinity relationships of phenylalkylamines as 5-HT2A ligands now be reinvestigated in greater detail.
• Synthesis of 2,3-dimethoxy-5-iodobenzoic acid
  作者：Eddy W. Yue、John M. Gerdes、Chester A. Mathis

  DOI：10.1021/jo00018a048

  日期：1991.8
• COENEN H. H., J. LABELLED COMPOUNDS AND RADIOPHARM., 1981, 18, NO 5, 739-746
  作者：COENEN H. H.

  DOI：——

  日期：——
• A structure-affinity study of the binding of 4-substituted analogs of 1-(2,5-dimethoxyphenyl)-2-aminopropane at 5-HT2 serotonin receptors
  作者：Mark R. Seggel、M. Y. Yousif、Robert A. Lyon、Milt Titeler、Bryan L. Roth、Eva A. Suba、Richard A. Glennon

  DOI：10.1021/jm00165a023

  日期：1990.3

  With [3H]ketanserin as the radioligand, structure-affinity relationships (SAFIRs) for binding at central 5-HT2 serotonin receptors (rat frontal cortex) were examined for a series of 27 4-substituted 1-(2,5-dimethoxyphenyl)-2-aminopropane derivatives (2,5-DMAs). The affinity (Ki values) ranged over a span of several orders of magnitude. It appears that the lipophilic character of the 4-position substituent plays a major role in determining the affinity of these agents for 5-HT2 receptors, 2,5-DMAs with polar 4-substituents (e.g. OH, NH2, COOH) display a very low affinity (Ki greater than 25,000 nM) for these receptors, whereas those with lipophilic functions display a significantly higher affinity. The results of these studies prompted us to synthesize and evaluate examples of newer lipophilic derivatives and several of these (e.g. n-hexyl, n-octyl) bind with very high (Ki values = 2.5 and 3 nM, respectively) affinities at central 5-HT2 sites. Although, 2,5-DMAs are generally considered to be 5-HT2 agonists, preliminary studies with isolated rat thoracic aorta suggest that some of the more lipophilic derivatives (e.g. the n-hexyl and n-octyl derivatives) are 5-HT2 antagonists.
• Iodine-125 labeled 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane: an iodinated radioligand that specifically labels the agonist high-affinity state of 5-HT2 serotonin receptors
  作者：Richard A. Glennon、Mark R. Seggel、William H. Soine、Katherine Herrick-Davis、Robert A. Lyon、Milt Titeler

  DOI：10.1021/jm00396a003

  日期：1988.1