tert-butyl (4-((benzyloxy)carbamoyl)phenyl)carbamate | 863666-11-9

• 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: tert-butyl (4-((benzyloxy)carbamoyl)phenyl)carbamate
• 英文别名: tert-butyl N-[4-(phenylmethoxycarbamoyl)phenyl]carbamate
• CAS: 863666-11-9
• 化学式: C₁₉H₂₂N₂O₄
• 分子量: 342.395
• InChiKey: PWRGOOPYNATTCX-UHFFFAOYSA-N

物化性质

• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  76.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (4-((benzyloxy)carbamoyl)phenyl)carbamate 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 2.0h， 生成 4-[(2-phenylacetyl)amino]-N-phenylmethoxybenzamide
  参考文献：
  名称：

  Structure-Based Optimization of Phenylbutyrate-Derived Histone Deacetylase Inhibitors

  摘要：

  Previously, we developed a strategy to develop a novel class of histone deacetylase (HDAC) inhibitors by tethering short-chain fatty acids with Zn2+-chelating motifs, which led to N-hydroxy-4-(4-phenylbutyryl-amino)benzamide (HTPB), a hydroxamate-tethered phenylbutyrate derivative with sub-micromolar potency in inhibiting HDAC activity and cancer cell proliferation. In this study, we carried out structure-based optimization of HTPB by using the framework generated by the structure of histone deacetylase-like protein (HDLP)-trichostatin A (TSA) complexes. Docking of HTPB into the HDLP binding domain suggested that the hydrophobic microenvironment encompassed by Phe-198 and Phe-200 could be exploited for structural optimization. This premise was corroborated by the greater potency of (S)-(+)-N-hydroxy-4-(3-methyl-2-phenylbutyrylamino)-benzamide [(S)-11] (IC50 in HDAC inhibition, 16 nM), of which the isopropyl moiety was favorable in interacting with this hydrophobic motif. (S)-11 at concentrations as low as 0.1 mu M was effective in causing histone hyperacetylation and p21(WAF/CIP1) overexpression and suppressing proliferation in cancer cells.

  DOI：

  10.1021/jm0503749
• 作为产物：
  描述：

  N-BOC-4-氨基苯甲酸 、 苄氧基胺盐酸盐 在 N,N-bis(2-oxo-3-oxazolidinyl)phosphoramidic chloride 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 tert-butyl (4-((benzyloxy)carbamoyl)phenyl)carbamate
  参考文献：
  名称：

  Structure-Based Optimization of Phenylbutyrate-Derived Histone Deacetylase Inhibitors

  摘要：

  Previously, we developed a strategy to develop a novel class of histone deacetylase (HDAC) inhibitors by tethering short-chain fatty acids with Zn2+-chelating motifs, which led to N-hydroxy-4-(4-phenylbutyryl-amino)benzamide (HTPB), a hydroxamate-tethered phenylbutyrate derivative with sub-micromolar potency in inhibiting HDAC activity and cancer cell proliferation. In this study, we carried out structure-based optimization of HTPB by using the framework generated by the structure of histone deacetylase-like protein (HDLP)-trichostatin A (TSA) complexes. Docking of HTPB into the HDLP binding domain suggested that the hydrophobic microenvironment encompassed by Phe-198 and Phe-200 could be exploited for structural optimization. This premise was corroborated by the greater potency of (S)-(+)-N-hydroxy-4-(3-methyl-2-phenylbutyrylamino)-benzamide [(S)-11] (IC50 in HDAC inhibition, 16 nM), of which the isopropyl moiety was favorable in interacting with this hydrophobic motif. (S)-11 at concentrations as low as 0.1 mu M was effective in causing histone hyperacetylation and p21(WAF/CIP1) overexpression and suppressing proliferation in cancer cells.

  DOI：

  10.1021/jm0503749

文献信息

• Structure-Based Optimization of Phenylbutyrate-Derived Histone Deacetylase Inhibitors
  作者：Qiang Lu、Da-Sheng Wang、Chang-Shi Chen、Yuan-Dong Hu、Ching-Shih Chen

  DOI：10.1021/jm0503749

  日期：2005.8.1

  Previously, we developed a strategy to develop a novel class of histone deacetylase (HDAC) inhibitors by tethering short-chain fatty acids with Zn2+-chelating motifs, which led to N-hydroxy-4-(4-phenylbutyryl-amino)benzamide (HTPB), a hydroxamate-tethered phenylbutyrate derivative with sub-micromolar potency in inhibiting HDAC activity and cancer cell proliferation. In this study, we carried out structure-based optimization of HTPB by using the framework generated by the structure of histone deacetylase-like protein (HDLP)-trichostatin A (TSA) complexes. Docking of HTPB into the HDLP binding domain suggested that the hydrophobic microenvironment encompassed by Phe-198 and Phe-200 could be exploited for structural optimization. This premise was corroborated by the greater potency of (S)-(+)-N-hydroxy-4-(3-methyl-2-phenylbutyrylamino)-benzamide [(S)-11] (IC50 in HDAC inhibition, 16 nM), of which the isopropyl moiety was favorable in interacting with this hydrophobic motif. (S)-11 at concentrations as low as 0.1 mu M was effective in causing histone hyperacetylation and p21(WAF/CIP1) overexpression and suppressing proliferation in cancer cells.
• From C ₁ to C ₃ : Copper‐Catalyzed <i>gem</i> ‐Bis(trifluoromethyl)olefination of α‐Diazo Esters with TMSCF ₃
  作者：Qian Wang、Chuanfa Ni、Mingyou Hu、Qiqiang Xie、Qinghe Liu、Shitao Pan、Jinbo Hu

  DOI：10.1002/anie.202002409

  日期：2020.5.25

  AbstractA Cu‐catalyzed gem‐bis(trifluoromethyl)olefination of α‐diazo esters, using TMSCF3 as the only fluorocarbon source, has been developed and provides an exquisite method to access gem‐bis(trifluoromethyl)alkenes. This unprecedented olefination process involves a carbene migratory insertion into “CuCF3” to generate the α‐CF3‐substituted organocopper species, which then undergoes β‐fluoride elimination and two consecutive addition‐elimination processes to give the desired products. The key to this efficient one‐pot C1‐to‐C3 synthetic protocol lies in the controllable double (over single and triple) trifluoromethylations of the gem‐difluoroalkene intermediates.