(S)-2-(4-isobutylphenyl)-N-((R)-1-phenylethyl)acetamide | 92761-68-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (S)-2-(4-isobutylphenyl)-N-((R)-1-phenylethyl)acetamide
• 英文别名: (2S)-N-benzyl-2-[4-(2-methylpropyl)phenyl]propanamide；(S)-N-benzyl-2-(4-isobutyl-phenyl)-propionamide；(S)-N-benzyl-2-(4-isobutylphenyl)propanamide；N-(benzyl)-2-(4-isobutylphenyl)propionamide；(S)-ibuprofen benzylamide
• CAS: 92761-68-7
• 化学式: C₂₀H₂₅NO
• 分子量: 295.425
• InChiKey: QQLPOACSDWBZPR-INIZCTEOSA-N

物化性质

• 沸点：
  483.5±34.0 °C(Predicted)
• 密度：
  1.022±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  (S)-(+)-布洛芬 在 吡啶 、 氯化亚砜 作用下， 以 丙酮 、 苯 为溶剂， 反应 17.0h， 生成 (S)-2-(4-isobutylphenyl)-N-((R)-1-phenylethyl)acetamide
  参考文献：
  名称：

  <p>Dexibuprofen amide derivatives as potential anticancer agents: synthesis, in silico docking, bioevaluation, and molecular dynamic simulation</p>

  摘要：

  Background: The amide derivatives of nonsteroidal anti-inflammatory drugs have been reported to possess antitumor activity. The present work describes the synthesis of dexibuprofen amide analogues (4a-j) as potential anticancer agents.Methods: The title amides (4a-j) were obtained by simple nucleophilic substitution reaction of dexibuprofen acid chloride with substituted amines in good yield and chemical structures were confirmed by FTIR, H-1 NMR, C-13 NMR and mass spectral data.Results: The brine shrimp lethality assay results showed that all of the synthesized compounds are non-toxic to shrimp larvae. The inhibitory effects on tumor growth were evaluated and it was observed that N-(2,5-dichlorophenyl)-2-(4-isobutylphenyl) propionamide (4e) and N-(2-chlorophenyl)-2-(4-isobutylphenyl) propionamide (4g) exhibited excellent antitumor activity compared to all other derivatives. The compound 4e bearing 2,5-dichloro substituted phenyl ring and 4g possesses 2-chioro substituted phenyl ring exhibited 100% inhibition of the tumor growth. The anticancer activity was evaluated against breast carcinoma cell line (MCF-7) and it was observed that derivative 4e exhibited excellent growth inhibition of cancer cells with IC50, value of 0.01 +/- 0.002 mu m, which is better than the standard drugs. The docking studies against breast cancer type 1 susceptibility protein BRCA1 (PDBID 3K0H) exhibited good binding affinities, which are in good agreement with the wet lab results. The compounds 4e and 4g showed the binding energy values of -6.39 and -6.34 Kcal/mol, respectively. The molecular dynamic (MD) simulation was also carried out to evaluate the residual flexibility of the best docking complexes of compounds 4e and 4g. The MD simulation analysis assured that the 4e formed a more stable complex with the target protein than the 4g. The synthesized amide derivatives exhibited were devoid of gastrointestinal side effects and no cytotoxic effects against human normal epithelial breast cell line (MCF-12A) were found.Conclusion: Based upon our wet lab and dry lab findings we propose that dexibuprofen analogue 4e may serve as a lead structure for the design of more potent anticancer drugs.

  DOI：

  10.2147/dddt.s178595

文献信息

• Palladium-Catalyzed Highly Regio- and Enantioselective Hydroesterification of Aryl Olefins with Phenyl Formate
  作者：Jingfu Li、Wenju Chang、Wenlong Ren、Jie Dai、Yian Shi

  DOI：10.1021/acs.orglett.6b02467

  日期：2016.11.4

  An effective Pd-catalyzed regio- and enantioselective hydroesterification of aryl olefins with phenyl formate is described. A variety of phenyl 2-arylpropanoates can be obtained in good yields with high b/l ratios and ee’s without using toxic CO gas.

  描述了芳基烯烃与甲酸苯基酯的有效的Pd催化的区域和对映选择性加氢酯化。无需使用有毒的CO气体，就可以以高的b / l比和ee以高收率获得各种2-芳基丙酸苯基酯。
• 光活性的2-芳基丙酸及其衍生物的合成方法
  申请人：南京大学

  公开号：CN106431919A

  公开（公告）日：2017-02-22

  本发明提供了一种光活性的2‑芳基丙酸及其衍生物的合成方法，所述方法通过金属钯盐、手性双磷配体为催化剂，使用原料易得的芳基烯烃与甲酸苯酯或一氧化碳、苯酚反应，得到光活性2‑芳基丙酸苯酯，并通过水解或者胺解得到光活性2‑芳基丙酸及其衍生物。所述合成方法反应条件温和、步骤简便、便于操作，且得到的光活性2‑芳基丙酸及其衍生物，对映体过量值(ee值)最高可达到95％。
• Catalytic Chemical Amide Synthesis at Room Temperature: One More Step Toward Peptide Synthesis
  作者：Tharwat Mohy El Dine、William Erb、Yohann Berhault、Jacques Rouden、Jérôme Blanchet

  DOI：10.1021/acs.joc.5b00378

  日期：2015.5.1

  An efficient method has been developed for direct amide bond synthesis between carboxylic acids and amines via (2-(thiophen-2-ylmethyl)phenyl)boronic acid as a highly active bench-stable catalyst. This catalyst was found to be very effective at room temperature for a large range of substrates with slightly higher temperatures required for challenging ones. This methodology can be applied to aliphatic

  已经开发出一种有效的方法，可以通过（2-（噻吩-2-基甲基）苯基）硼酸作为一种高活性的台式稳定催化剂，直接在羧酸和胺之间合成酰胺键。发现该催化剂在室温下对于大范围的底物非常有效，而具有挑战性的底物需要稍高的温度。该方法可以应用于脂族，α-羟基，芳族和杂芳族酸以及伯，仲，杂环，甚至官能化胺。值得注意的是，N -Boc保护的氨基酸以良好的产率成功地偶联，而消旋作用很小。报道了催化二肽合成的一个例子。
• Direct Synthesis of Amides from Carboxylic Acids and Amines Using B(OCH₂CF₃)₃
  作者：Rachel M. Lanigan、Pavel Starkov、Tom D. Sheppard

  DOI：10.1021/jo400509n

  日期：2013.5.3

  range of amines. In most cases, the amide products can be purified by a simple filtration procedure using commercially available resins, with no need for aqueous workup or chromatography. The amidation of N-protected amino acids with both primary and secondary amines proceeds effectively, with very low levels of racemization. B(OCH2CF3)3 can also be used for the formylation of a range of amines in good

  B(OCH 2 CF 3 ) 3由易得的B 2 O 3和2,2,2-三氟乙醇制备，是一种有效的试剂，可用于多种羧酸与多种胺的直接酰胺化。在大多数情况下，可以使用市售树脂通过简单的过滤程序纯化酰胺产物，无需进行水处理或色谱法。N-保护的氨基酸与伯胺和仲胺的酰胺化有效进行，外消旋化水平非常低。B(OCH 2 CF 3 ) 3 通过二甲基甲酰胺的转酰胺基作用，也可用于一系列胺的甲酰化反应，收率良好至极好。
• Amidation of unactivated ester derivatives mediated by trifluoroethanol
  作者：Christopher G. McPherson、Nicola Caldwell、Craig Jamieson、Iain Simpson、Allan J. B. Watson

  DOI：10.1039/c7ob00593h

  日期：——

  A catalytic amidation protocol mediated by 2,2,2-trifluoroethanol has been developed, facilitating the condensation of unactivated esters and amines, furnishing both secondary and tertiary amides. The complete scope and limitations of the method are described, along with modified conditions for challenging substrates such as acyclic secondary amines and chiral esters with retention of chiral integrity

  已经开发了由2,2,2-三氟乙醇介导的催化酰胺化方案，可促进未活化的酯和胺的缩合，同时提供仲酰胺和叔酰胺。描述了该方法的完整范围和局限性，以及具有挑战性的底物（如无环仲胺和手性酯）的修饰条件，并保留了手性完整性。