N-(2-hydroxyphenyl)-2-propylpentanamide

• 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-hydroxyphenyl)-2-propylpentanamide
• 英文别名: N-(2-Hydroxyphenyl)-2-propylpentanamide
• 化学式: C₁₄H₂₁NO₂
• 分子量: 235.326
• InChiKey: GPXMBIJLAKLRAN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  丙戊酸 在 氯化亚砜 、 三乙胺 作用下， 以 乙腈 为溶剂， 反应 49.0h， 生成 N-(2-hydroxyphenyl)-2-propylpentanamide
  参考文献：
  名称：

  新型丙戊酸氨基酚酰胺具有增强的神经胶质细胞生存力效果†

  摘要：

  通过将丙戊酰氯与邻氨基苯酚偶联，合成新的丙戊酸衍生物，得到七种N-（邻羟苯基）丙酰胺。这些酰胺具有相似的结构特征，并且在没有特定取代基的情况下，或者通过包含供电子（–Me），电撤离（​​–NO 2）或pi电捐赠/ sigma电撤消（–）表现出可调节的电子和空间贡献。-Cl）取代基在芳环上。此类衍生物的身份通过使用FTIR，1 H，13的光谱表征得到证明C和HETCOR NMR，以及通过分析它们的熔点。尤其是，对于三种衍生物，确定其在结晶相中的化学结构是可行的。这三个分子都以相似的方式表现，并且表现出非常相似的构象，而与所连接的取代基无关。与VPA相比，发现该基本化合物在C6细胞中的活性高出15.8倍，在U373细胞中的活性高出4.4倍。通常，母体化合物或具有-Me取代基的化合物对C6细胞的影响要大于U373细胞。但是，在两个细胞系中，具有–NO 2和–Cl取代基以及VPA的化合物对IC 50的剂量要求相似。用–Me或–NO

  DOI：

  10.1039/c7ra00048k

文献信息

• N-(2-hydroxyphenyl)-2-propylpentanamide, a valproic acid aryl derivative designed <i>in silico</i> with improved anti-proliferative activity in HeLa, rhabdomyosarcoma and breast cancer cells
  作者：Berenice Prestegui-Martel、Jorge Antonio Bermúdez-Lugo、Alma Chávez-Blanco、Alfonso Dueñas-González、José Rubén García-Sánchez、Oscar Alberto Pérez-González、Itzia Irene Padilla-Martínez、Manuel Jonathan Fragoso-Vázquez、Jessica Elena Mendieta-Wejebe、Ana María Correa-Basurto、David Méndez-Luna、José Trujillo-Ferrara、José Correa-Basurto

  DOI：10.1080/14756366.2016.1210138

  日期：2016.11.3

  Epigenetic alterations are associated with cancer and their targeting is a promising approach for treatment of this disease. Among current epigenetic drugs, histone deacetylase (HDAC) inhibitors induce changes in gene expression that can lead to cell death in tumors. Valproic acid (VPA) is a HDAC inhibitor that has antitumor activity at mM range. However, it is known that VPA is a hepatotoxic drug. Therefore, the aim of this study was to design a set of VPA derivatives adding the arylamine core of the suberoylanilide hydroxamic acid (SAHA) with different substituents at its carboxyl group. These derivatives were submitted to docking simulations to select the most promising compound. The compound 2 (N-(2-hydroxyphenyl)-2-propylpentanamide) was the best candidate to be synthesized and evaluated in vitro as an anti-cancer agent against HeLa, rhabdomyosarcoma and breast cancer cell lines. Compound 2 showed a better IC50 (M range) than VPA (mM range) on these cancer cells. And also, 2 was particularly effective on triple negative breast cancer cells. In conclusion, 2 is an example of drugs designed in silico that show biological properties against human cancer difficult to treat as triple negative breast cancer.
• Anti-epileptic activity, toxicity and teratogenicity in CD1 mice of a novel valproic acid arylamide derivative, N-(2-hydroxyphenyl)-2-propylpentanamide
  作者：José Melesio Cristóbal-Luna、José Correa-Basurto、Humberto L. Mendoza-Figueroa、Germán Chamorro-Cevallos

  DOI：10.1016/j.taap.2020.115033

  日期：2020.7

  N-(2-hydroxyphenyl)-2-propylpentamide (HO-AAVPA) is a novel arylamide derivative of valproic acid (VPA) designed in silico, with better antioxidant and antiproliferative effect on cancer cell lines than VPA. This study was aimed to evaluate the anticonvulsant activity, the toxicity and teratogenicity produced in HO-AAVPA-treated CD1 mice using VPA as positive control. With the maximal electroshock (MES)- and pentylenetetrazole (PTZ)-induced seizure models, HO-AAVPA reduced the time of hind limb extension, stupor and recovery, the number of clonic and tonic seizures and the mortality rate in a dose-dependent manner, obtaining an ED50 of 370 and 348 mg/kg for MES and PTZ, respectively. On the rotarod test, mice administered with 600 mg/kg HO-AAVPA manifested reduced locomotor activity (2.78%); while HO-AAVPA at 300 mg/kg and VPA at 500 mg/kg gave a similar outcome (similar to 60%). The LD50 of 936.80 mg/kg herein found for HO-AAVPA reflects moderate toxicity. Concerning teratogenicity, the administration of HO-AAVPA to pregnant females at 300 and 600 mg/kg on gestation day (GD) 8.5 generated less visceral and skeletal alterations in the fetuses, as well as, minor rate of modifications in the expression pattern of the neuronal marker Tuj1 and endothelial marker PECAM1 in embryos, that those induced by VPA administration. Altered embryonic development occurred with less frequency and severity with HO-AAVPA at 600 mg/kg than VPA at 500 mg/kg. In conclusion, the protective effect against convulsions provided by HO-AAVPA was comparable to that of VPA in the MES and PZT seizure models, showed lower toxicity and less damage to embryonic and fetal development.
• Novel valproic aminophenol amides with enhanced glial cell viability effect
  作者：Andrea Alpuche-García、Xochitl Dávila-González、Leticia Arregui、Hiram I. Beltrán

  DOI：10.1039/c7ra00048k

  日期：——

  structural characteristics and exhibit tuneable electronic and steric contributions either without particular substituents, or through the inclusion of electro-donating (–Me), electro-withdrawing (–NO2) or pi electro-donating/sigma electro-withdrawing (–Cl) substituents at the aromatic ring. The identity of such derivatives was evidenced through spectroscopic characterization using FTIR, 1H, 13C and

  通过将丙戊酰氯与邻氨基苯酚偶联，合成新的丙戊酸衍生物，得到七种N-（邻羟苯基）丙酰胺。这些酰胺具有相似的结构特征，并且在没有特定取代基的情况下，或者通过包含供电子（–Me），电撤离（​​–NO 2）或pi电捐赠/ sigma电撤消（–）表现出可调节的电子和空间贡献。-Cl）取代基在芳环上。此类衍生物的身份通过使用FTIR，1 H，13的光谱表征得到证明C和HETCOR NMR，以及通过分析它们的熔点。尤其是，对于三种衍生物，确定其在结晶相中的化学结构是可行的。这三个分子都以相似的方式表现，并且表现出非常相似的构象，而与所连接的取代基无关。与VPA相比，发现该基本化合物在C6细胞中的活性高出15.8倍，在U373细胞中的活性高出4.4倍。通常，母体化合物或具有-Me取代基的化合物对C6细胞的影响要大于U373细胞。但是，在两个细胞系中，具有–NO 2和–Cl取代基以及VPA的化合物对IC 50的剂量要求相似。用–Me或–NO