N-(4-acetylphenyl)hexanamide | 348163-48-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-(4-acetylphenyl)hexanamide
• CAS: 348163-48-4
• 化学式: C₁₄H₁₉NO₂
• mdl: MFCD00442528
• 分子量: 233.31
• InChiKey: ZTTZMEJRHAFANA-UHFFFAOYSA-N

物化性质

• 沸点：
  426.0±28.0 °C(Predicted)
• 密度：
  1.060±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.428
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(4-acetylphenyl)hexanamide 、 氨基硫脲 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 1-(4-hexanamidophenyl)ethylidenethiosemicarbazide
  参考文献：
  名称：

  Structure-based modification of 3-/4-aminoacetophenones giving a profound change of activity on tyrosinase: From potent activators to highly efficient inhibitors

  摘要：

  In this study, we developed 3-/4-aminoacetophenones and their structure-based 3-/4-aminophenylethylidenethiosemicarbazide derivatives, respectively, as novel tyrosinase activators and inhibitors. Notably, all the obtained thiosemicarbazones displayed more potent tyrosinase inhibitory activities than kojic acid. Especially, compound 7k was found to be the most active tyrosinase inhibitor with IC50 value of 0.291 mu M. The structure-activity relationships (SARs) analysis showed that: (1) the amine group was absolutely necessarily for determining the tyrosinase activation activity; (2) the introduction of thiosemicarbazide group played a very vital role in transforming tyrosinase activators into tyrosinase inhibitors; (3) the phenylethylenethiosemicarbazide moiety was crucial for determining the tyrosinase inhibitory activity; (4) the type of acyl group had no obvious effect on the inhibitory activity; (5) the position of amide substituent on the phenyl ring influenced the tyrosinase inhibitory potency. Moreover, the inhibition mechanism and inhibition kinetics study revealed that compound 7k was reversible and non-competitive inhibitor, and compound 8h was reversible and competitive-uncompetitive mixed-II type inhibitor. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.02.013
• 作为产物：
  描述：

  己酰胺 、 对氯苯乙酮 在 tris-(dibenzylideneacetone)dipalladium(0) potassium phosphate 、 3 A molecular sieve 作用下， 以 叔丁醇 为溶剂， 反应 19.0h， 以83%的产率得到N-(4-acetylphenyl)hexanamide
  参考文献：
  名称：

  Pd-Catalyzed Amidations of Aryl Chlorides Using Monodentate Biaryl Phosphine Ligands:  A Kinetic, Computational, and Synthetic Investigation

  摘要：

  We present results on the amidation of aryl halides and sulfonates utilizing a monodentate biaryl phosphine-Pd catalyst. Our results are in accord with a previous report that suggests that the formation of K-2-amidate complexes is deleterious to the effectiveness of a catalyst for this transformation and that their formation can be prevented by the use of appropriate bidentate ligands. We now provide data that suggest that the use of certain monodentate ligands can also prevent the formation of the K-2-amidate complexes and thereby generate more stable catalysts for the amination of aryl chlorides. Furthermore, computational studies shed light on the importance of the key feature(s) of the biaryl phosphines (a methyl group ortho to the phosphorus center) that enable the coupling to occur. The use of ligands that possess a methyl group ortho to the phosphorus center allows a variety of aryl and heteroaryl chlorides with various amides to be coupled in high yield.

  DOI：

  10.1021/ja0717414

文献信息

• Improvement of Pharmacological Properties of Irreversible Thyroid Receptor Coactivator Binding Inhibitors
  作者：Jong Yeon Hwang、Leggy A. Arnold、Fangyi Zhu、Aaron Kosinski、Thomas J. Mangano、Vincent Setola、Bryan L. Roth、R. Kiplin Guy

  DOI：10.1021/jm9002704

  日期：2009.7.9

  We have previously reported the discover), and preliminary structure activity relationships of a series of beta-aminoketones that disrupt the binding of coactivators to TR. However, the most active compounds had moderate inhibitory potency and relatively high cytotoxicity, resulting in narrow therapeutic index. Additionally, preliminary evaluation of in vivo toxicology revealed a significant dose related cardiotoxicity. Here we describe the improvement of pharmacological properties of thyroid hormone receptor coactivator binding inhibitors. A comprehensive Survey of the effects of substitutents in key areas of the molecule was carried out based on mechanistic insight from the earlier report. This study revealed that both electron withdrawing and hydrophobic substituents on the aromatic ring led to higher potency. On the other hand, moving from an alkyl to a sulfonyl alkyl side chain led to reduced cytotoxicity, Finally, utilization of airline moieties having low pK(a)'s resulted in lowered ion channel activity without any loss of pharmacological activity.