4-(4-苯基甲氧基羰基苯氧基)苯甲酸 | 918797-35-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-(4-苯基甲氧基羰基苯氧基)苯甲酸
• 英文名称: 4-(4-(benzyloxycarbonyl)phenoxy)benzoic acid
• 英文别名: 4-{4-[(Benzyloxy)carbonyl]phenoxy}benzoic acid；4-(4-phenylmethoxycarbonylphenoxy)benzoic acid
• CAS: 918797-35-0
• 化学式: C₂₁H₁₆O₅
• 分子量: 348.355
• InChiKey: NNVHGXFZJRNFFY-UHFFFAOYSA-N

物化性质

• 沸点：
  530.9±40.0 °C(Predicted)
• 密度：
  1.284±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(4-苯基甲氧基羰基苯氧基)苯甲酸 在 palladium on activated charcoal N-甲基吗啉 、 氢气 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 propyl (2S)-2-[[(2S)-2-[[4-[4-[[(2S,3S)-1-[[(3S,4S)-1-(butylamino)-3-hydroxy-6-methyl-1-oxoheptan-4-yl]amino]-3-methyl-1-oxopentan-2-yl]carbamoyl]phenoxy]benzoyl]amino]-4-methylpentanoyl]amino]-6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoate
  参考文献：
  名称：

  High Antiplasmodial Activity of Novel Plasmepsins I and II Inhibitors

  摘要：

  The aim of this study was to develop new antiplasmodial compounds acting through distinct mechanisms during both the liver and the blood stages of the parasite life cycle. Compounds were designed on the basis of the "double-drug" approach: primaquine, which has been linked to statine-based inhibitors of plasmepsins (PLMs), the plasmodial aspartic proteases involved in degradation of hemeoglobin. The compounds were tested in vitro for anti-PLM I/PLM II activities and against chloroquine-sensitive (D10) and chloroquine-resistant (W2) strains of P. falciparum. An antiplasmodial activity (IC50) as low as 0.1 mu M was obtained, an excellent improvement in comparison with inhibitors previously reported (IC50 = 2 - 20 mu M). The killing activity was equally directed against both P. falciparum strains and was correlated to lipophilicity (calculated as ALogP), for all compounds but one (9). All compounds inhibited PLM I and PLM II in the nanomolar range (K-i = 1 - 700 nM). The most promising compounds (2, 6, 10) were not cytotoxic against human fibroblasts at 100 mu M and were highly selective for PLMs vs human cathepsin D.

  DOI：

  10.1021/jm061033d
• 作为产物：
  描述：

  4,4'-二苯醚二甲酸 、 溴甲苯 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以32%的产率得到4-(4-苯基甲氧基羰基苯氧基)苯甲酸
  参考文献：
  名称：

  High Antiplasmodial Activity of Novel Plasmepsins I and II Inhibitors

  摘要：

  The aim of this study was to develop new antiplasmodial compounds acting through distinct mechanisms during both the liver and the blood stages of the parasite life cycle. Compounds were designed on the basis of the "double-drug" approach: primaquine, which has been linked to statine-based inhibitors of plasmepsins (PLMs), the plasmodial aspartic proteases involved in degradation of hemeoglobin. The compounds were tested in vitro for anti-PLM I/PLM II activities and against chloroquine-sensitive (D10) and chloroquine-resistant (W2) strains of P. falciparum. An antiplasmodial activity (IC50) as low as 0.1 mu M was obtained, an excellent improvement in comparison with inhibitors previously reported (IC50 = 2 - 20 mu M). The killing activity was equally directed against both P. falciparum strains and was correlated to lipophilicity (calculated as ALogP), for all compounds but one (9). All compounds inhibited PLM I and PLM II in the nanomolar range (K-i = 1 - 700 nM). The most promising compounds (2, 6, 10) were not cytotoxic against human fibroblasts at 100 mu M and were highly selective for PLMs vs human cathepsin D.

  DOI：

  10.1021/jm061033d

文献信息

• Discovery of oxybisbenzoylamides as a new class of antimalarial agents
  作者：A. Pancotti、S. Parapini、M. Dell'Agli、L. Gambini、C. Galli、E. Sangiovanni、N. Basilico、E. Bosisio、D. Taramelli、S. Romeo

  DOI：10.1039/c5md00115c

  日期：——

  A new antimalarial pharmacophore has been obtained starting from previously described dual inhibitors of Plasmodium falciparum.

  从先前描述的疟原虫的双重抑制剂出发，得到了一种新的抗疟药物药效团。
• Antiplasmodial activities of 4-aminoquinoline–statine compounds
  作者：Nadia Vaiana、Melissa Marzahn、Silvia Parapini、Peng Liu、Mario Dell’Agli、Andrea Pancotti、Enrico Sangiovanni、Nicoletta Basilico、Enrica Bosisio、Ben M. Dunn、Donatella Taramelli、Sergio Romeo

  DOI：10.1016/j.bmcl.2012.07.069

  日期：2012.9

  We report the discovery of new potent inhibitors of the growth of Plasmodium falciparum chloroquine (CQ)-resistant W2 strain. These compounds were designed using the double drug approach by introducing a residue able to enhance the accumulation of plasmepsins inhibitors into the food vacuole. Some of the molecules were more active than CQ against CQ-resistant strain and showed good selectivity against cathepsin D. (C) 2012 Elsevier Ltd. All rights reserved.
• Plasmepsin II inhibition and antiplasmodial activity of Primaquine–Statine `double-drugs'
  作者：Sergio Romeo、Mario Dell'Agli、Silvia Parapini、Luca Rizzi、Germana Galli、Monica Mondani、Anna Sparatore、Donatella Taramelli、Enrica Bosisio

  DOI：10.1016/j.bmcl.2004.03.030

  日期：2004.6

  Statine-based inhibitors of Plasmepsin II (PLMII) coupled with Primaquine have been designed using the 'double-drug' approach. The IC50 values for PLMII inhibition ranged from 0.59 to 400 nM and the best IC50 value for inhibition of Plasmodium falciparum growth in vitro was 0.4 muM, which represent a remarkable improvement compared to other statine-based PLMII inhibitors. (C) 2004 Elsevier Ltd. All rights reserved.
• High Antiplasmodial Activity of Novel Plasmepsins I and II Inhibitors
  作者：Mario Dell'Agli、Silvia Parapini、Germana Galli、Nadia Vaiana、Donatella Taramelli、Anna Sparatore、Peng Liu、Ben M. Dunn、Enrica Bosisio、Sergio Romeo

  DOI：10.1021/jm061033d

  日期：2006.12.1

  The aim of this study was to develop new antiplasmodial compounds acting through distinct mechanisms during both the liver and the blood stages of the parasite life cycle. Compounds were designed on the basis of the "double-drug" approach: primaquine, which has been linked to statine-based inhibitors of plasmepsins (PLMs), the plasmodial aspartic proteases involved in degradation of hemeoglobin. The compounds were tested in vitro for anti-PLM I/PLM II activities and against chloroquine-sensitive (D10) and chloroquine-resistant (W2) strains of P. falciparum. An antiplasmodial activity (IC50) as low as 0.1 mu M was obtained, an excellent improvement in comparison with inhibitors previously reported (IC50 = 2 - 20 mu M). The killing activity was equally directed against both P. falciparum strains and was correlated to lipophilicity (calculated as ALogP), for all compounds but one (9). All compounds inhibited PLM I and PLM II in the nanomolar range (K-i = 1 - 700 nM). The most promising compounds (2, 6, 10) were not cytotoxic against human fibroblasts at 100 mu M and were highly selective for PLMs vs human cathepsin D.