3-(tert-butyloxycarbonyl)phenylacetic acid | 342624-55-9

• 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: 3-(tert-butyloxycarbonyl)phenylacetic acid
• 英文别名: 2-{3-[(Tert-butoxy)carbonyl]phenyl}acetic acid；2-[3-[(2-methylpropan-2-yl)oxycarbonyl]phenyl]acetic acid
• CAS: 342624-55-9
• 化学式: C₁₃H₁₆O₄
• 分子量: 236.268
• InChiKey: BPNNUFURMIUVRW-UHFFFAOYSA-N

物化性质

• 沸点：
  371.9±25.0 °C(Predicted)
• 密度：
  1.156±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(tert-butyloxycarbonyl)phenylacetic acid 在 N,N-二甲基甲酰胺 草酰氯 、 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 cis-3-benzyl-4-[4'-(tert-butyloxycarbonyl)benzyloxycarbonyl]-1-{3'-[tert-butyloxycarbonyl]phenylacetate}-2-azetidinone
  参考文献：
  名称：

  Design, Synthesis, and Proposed Active Site Binding Analysis of Monocyclic 2-Azetidinone Inhibitors of Prostate Specific Antigen

  摘要：

  A homology derived molecular model of prostate specific antigen (PSA) was created and refined. The active site region was investigated for specific interacting functionality and a binding model postulated for the novel 2-azetidinone acyl enzyme inhibitor 1 (IC50 = 8.98 +/- 0.90 muM) which was used as a lead compound in this study. A single low energy conformation structure II (Figure 2) was adopted as most likely to represent binding after minimization and dynamics calculations. Systematic analysis of the binding importance of all three side chains appended to the 2-azetidinone was conducted by the synthesis of several analogues. A proposed salt bridge to Lys-145 with 4 (IC50 = 5.84 +/- 0.92 muM) gave improved inhibition, but generally the binding of the N-1 side chain in a specific secondary aromatic binding site did not tolerate much structural alteration. A hydrophobic interaction of the C-4 side chain afforded inhibitor 6 (IC50 = 1.43 +/- 0.19 muM), and polar functionality could also be added in a proposed interaction with Gln-166 in 5 (IC50 = 1.34 +/- 0.05 muM). Reversal of the C-4 ester connectivity furnished inhibitors 7 (IC50 = 1 59 +/- 0 15 muM), 11 (IC50 = 3.08 +/- 0.41 muM), and 13 (IC50 = 2.19 +/- 0.36 muM) which were perceived to bind to PSA by a rotation of 180 degrees relative to the C-4 ester of normal connectivity. Incorporation of hydroxyl functionality into the C-3 side chain provided 16 (IC50 = 348 +/- 50 nM) with the greatest increase in PSA inhibition by a single modification. Multiple copy simultaneous search (MCSS) analysis of the PSA active site further supported our model and suggested that 18 would bind strongly. Asymmetric synthesis yielded 18 (IC50 = 226 +/- 10 nM) as the most potent inhibitor of PSA reported to date. It is concluded that our design approach has been successful in developing PSA inhibitors and could also be applied to the inhibition of other enzymes, especially in the absence of crystallographic information.

  DOI：

  10.1021/jm000145g
• 作为产物：
  描述：

  间苯二甲酸 在 palladium on activated charcoal 、 N,N-二甲基甲酰胺 草酰氯 、 三氟化硼乙醚 、 氢气 、 溶剂黄146 、 三乙胺 、 silver(l) oxide 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 环己烷 、 水 、 乙酸乙酯 、 苯 为溶剂， 反应 32.0h， 生成 3-(tert-butyloxycarbonyl)phenylacetic acid
  参考文献：
  名称：

  Design, Synthesis, and Proposed Active Site Binding Analysis of Monocyclic 2-Azetidinone Inhibitors of Prostate Specific Antigen

  摘要：

  A homology derived molecular model of prostate specific antigen (PSA) was created and refined. The active site region was investigated for specific interacting functionality and a binding model postulated for the novel 2-azetidinone acyl enzyme inhibitor 1 (IC50 = 8.98 +/- 0.90 muM) which was used as a lead compound in this study. A single low energy conformation structure II (Figure 2) was adopted as most likely to represent binding after minimization and dynamics calculations. Systematic analysis of the binding importance of all three side chains appended to the 2-azetidinone was conducted by the synthesis of several analogues. A proposed salt bridge to Lys-145 with 4 (IC50 = 5.84 +/- 0.92 muM) gave improved inhibition, but generally the binding of the N-1 side chain in a specific secondary aromatic binding site did not tolerate much structural alteration. A hydrophobic interaction of the C-4 side chain afforded inhibitor 6 (IC50 = 1.43 +/- 0.19 muM), and polar functionality could also be added in a proposed interaction with Gln-166 in 5 (IC50 = 1.34 +/- 0.05 muM). Reversal of the C-4 ester connectivity furnished inhibitors 7 (IC50 = 1 59 +/- 0 15 muM), 11 (IC50 = 3.08 +/- 0.41 muM), and 13 (IC50 = 2.19 +/- 0.36 muM) which were perceived to bind to PSA by a rotation of 180 degrees relative to the C-4 ester of normal connectivity. Incorporation of hydroxyl functionality into the C-3 side chain provided 16 (IC50 = 348 +/- 50 nM) with the greatest increase in PSA inhibition by a single modification. Multiple copy simultaneous search (MCSS) analysis of the PSA active site further supported our model and suggested that 18 would bind strongly. Asymmetric synthesis yielded 18 (IC50 = 226 +/- 10 nM) as the most potent inhibitor of PSA reported to date. It is concluded that our design approach has been successful in developing PSA inhibitors and could also be applied to the inhibition of other enzymes, especially in the absence of crystallographic information.

  DOI：

  10.1021/jm000145g

文献信息

• Compositions of lipopeptide antibiotic derivatives and methods of use thereof
  申请人：Cameron R. Dale

  公开号：US20050153876A1

  公开（公告）日：2005-07-14

  The present invention provides derivatives of lipopeptide antibiotics that display antimicrobial activity against microorganisms, methods and compounds for synthesizing such antimicrobial derivatives and analogues, and methods of using the compounds in a variety of contexts, including in the treatment and prevention of microbial infections.

  本发明提供了脂肽类抗生素的衍生物，对微生物显示出抗菌活性，包括合成这种抗微生物衍生物和类似物的方法和化合物，以及在多种情况下使用这些化合物的方法，包括在治疗和预防微生物感染中使用。
• US7868135B2
  申请人：——

  公开号：US7868135B2

  公开（公告）日：2011-01-11