N-cyclohexyl-2,2,2-triphenylacetamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: N-cyclohexyl-2,2,2-triphenylacetamide
• 化学式: C₂₆H₂₇NO
• 分子量: 369.506
• InChiKey: RJCTYKOBJOHGTQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 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：

  三苯基乙酸 在 4-二甲氨基吡啶 、 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 60.0h， 生成 N-cyclohexyl-2,2,2-triphenylacetamide
  参考文献：
  名称：

  Synthesis and Identification of Small Molecules that Potently Induce Apoptosis in Melanoma Cells through G1 Cell Cycle Arrest

  摘要：

  Late-stage malignant melanoma is a cancer that is refractory to current chemotherapeutic treatments. The average survival time for patients with such a diagnosis is 6 months. In general, the vast majority of anticancer drugs operate through induction of cell cycle arrest and cell death in either the DNA synthesis (S) or mitosis (M) phase of the cell cycle. Unfortunately, the same mechanisms that melanocytes possess to protect cells from DNA damage often confer resistance to drugs that derive their toxicity from S or M phase arrest. Described herein is the synthesis of a combinatorial library of potential proapoptotic agents and the subsequent identification of a class of small molecules (triphenyl methylamides, TPMAs) that arrest the growth of melanoma cells in the G1 phase of the cell cycle. Several of these TPMAs are quite potent inducers of apoptotic death in melanoma cell lines (IC50 similar to 0.5 mu M), and importantly, some TPMAs are comparatively nontoxic to normal cells isolated from the bone marrow of healthy donors. Furthermore, the TPMAs were found to dramatically reduce the level of active nuclear factor kappa-B (NF kappa B) in the cell; NF kappa B is known to be constitutively active in melanoma, and this activity is critical for the proliferation of melanoma cells and their evasion of apoptosis. Compounds that reduce the level of NF kappa B and arrest cells in the G1 phase of the cell cycle can provide insights into the biology of melanoma and may be effective antimelanoma agents.

  DOI：

  10.1021/ja042913p

文献信息

• Amine Activation:<i>N</i>-Arylamino Acid Amide Synthesis from Isothioureas and Amino Acids
  作者：Yan-Ping Zhu、Pieter Mampuys、Sergey Sergeyev、Steven Ballet、Bert U. W. Maes

  DOI：10.1002/adsc.201700134

  日期：2017.7.17

  functional group compatibility, with respect to side chain functionality of the amino acid (e. g. aliphatic and aromatic OH, (hetero)aromatic NH, amide NH, thioether), and the chiral amino acids do not undergo epimerization. The mechanism of the new amide synthesis has been studied.

  Ñ -arylamino酰胺已经通过基于新方法被合成ñ -芳基胺活化成异硫脲，随后用下铁催化氨基酸反应。可以使用三组分反应与市售试剂叔丁基异氰化物和S-苯基苯硫代磺酸盐轻松地制备活化的N-芳基胺。相对于氨基酸（例如脂族和芳族OH，（杂）芳族NH，酰胺NH，硫醚）的侧链官能度，该方案显示出广泛的官能团相容性，并且手性氨基酸不发生差向异构化。已经研究了新酰胺合成的机理。
• Nickel-Catalyzed Reductive Addition of Aryl/Benzyl Halides and Pseudohalides to Carbodiimides for the Synthesis of Amides
  作者：Farhad Panahi、Fereshteh Jamedi、Nasser Iranpoor

  DOI：10.1002/ejoc.201501349

  日期：2016.2

  A Nickel-catalyzed reductive process is described for the direct amidation of benzyl and aryl halides using carbodiimides as the amidating agent. Moreover, aryl and benzyl C–O electrophiles such as triflate, acetate, tosylate, trityl ether, and pivalate were converted into amides using this method. The in-situ-generated Ni0 acts as a catalyst for the reaction at room temperature for benzylic substrates

  描述了使用碳二亚胺作为酰胺化剂直接酰胺化苄基和芳基卤化物的镍催化还原方法。此外，芳基和苄基 C-O 亲电试剂，如三氟甲磺酸酯、乙酸酯、甲苯磺酸酯、三苯甲基醚和新戊酸酯，使用该方法转化为酰胺。原位生成的 NiO 充当室温下苄基底物和 70°C 芳基亲电试剂反应的催化剂。这种新的镍催化还原偶联方案为使用碳二亚胺合成各种酰胺提供了一种通用且操作简单的方法。带有大取代基的酰胺可以通过这种策略以高产率合成，这证明了其在酰胺合成中的有效性。
• Indifference to Hydrogen Bonding in a Family of Secondary Amides
  作者：D. Tyler McQuade、Sonya L. McKay、Douglas R. Powell、Samuel H. Gellman

  DOI：10.1021/ja9711019

  日期：1997.9.1

  N-H stretch region IR spectroscopy has been used to probe the hydrogen bond-donating properties of six structurally related secondary amides in which the amide group is flanked by sterically bulky groups. For three of the compounds, solid state IR analysis reveals N-R stretch bands >3400 cm(-1), which suggests the absence of intermolecular N-H-O=C hydrogen bonds. Crystallographic data for these three amides confirm the absence of a standard N-H-O=C interaction. For the other three amides, N-H stretch bands in the range 3370-3290 cm(-1) suggest the occurrence of intermolecular N-H-O=C hydrogen bonds in the solid state, but high quality crystals could not be grown. Steric hindrance to hydrogen bond donation by these amides is manifested in IR data obtained in DMSO: although this solvent is a strong hydrogen bond acceptor, N-H stretch bands are observed for both solvent-hydrogen bonded and non-hydrogen bonded amide groups. The amides described here and related compounds should be useful for calibrating spectroscopic methods that are intended to detect hydrogen bond formation.
• Synthesis and Identification of Small Molecules that Potently Induce Apoptosis in Melanoma Cells through G1 Cell Cycle Arrest
  作者：Robin S. Dothager、Karson S. Putt、Brittany J. Allen、Benjamin J. Leslie、Vitaliy Nesterenko、Paul J. Hergenrother

  DOI：10.1021/ja042913p

  日期：2005.6.1

  Late-stage malignant melanoma is a cancer that is refractory to current chemotherapeutic treatments. The average survival time for patients with such a diagnosis is 6 months. In general, the vast majority of anticancer drugs operate through induction of cell cycle arrest and cell death in either the DNA synthesis (S) or mitosis (M) phase of the cell cycle. Unfortunately, the same mechanisms that melanocytes possess to protect cells from DNA damage often confer resistance to drugs that derive their toxicity from S or M phase arrest. Described herein is the synthesis of a combinatorial library of potential proapoptotic agents and the subsequent identification of a class of small molecules (triphenyl methylamides, TPMAs) that arrest the growth of melanoma cells in the G1 phase of the cell cycle. Several of these TPMAs are quite potent inducers of apoptotic death in melanoma cell lines (IC50 similar to 0.5 mu M), and importantly, some TPMAs are comparatively nontoxic to normal cells isolated from the bone marrow of healthy donors. Furthermore, the TPMAs were found to dramatically reduce the level of active nuclear factor kappa-B (NF kappa B) in the cell; NF kappa B is known to be constitutively active in melanoma, and this activity is critical for the proliferation of melanoma cells and their evasion of apoptosis. Compounds that reduce the level of NF kappa B and arrest cells in the G1 phase of the cell cycle can provide insights into the biology of melanoma and may be effective antimelanoma agents.