3-methoxymethoxy-3-(4-nitrophenyl)-propan-1-ol | 263392-94-5

• 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-methoxymethoxy-3-(4-nitrophenyl)-propan-1-ol
• 英文别名: 3-methoxymethoxy-3-(4-nitrophenyl)propan-1-ol；3-(Methoxymethoxy)-3-(4-nitrophenyl)propan-1-ol
• CAS: 263392-94-5
• 化学式: C₁₁H₁₅NO₅
• 分子量: 241.244
• InChiKey: NTYNPRKRQGQHLB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  84.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-methoxymethoxy-3-(4-nitrophenyl)-propan-1-ol 在 sodium azide 、 15-冠醚-5 、 B-溴代邻苯二氧硼烷 、 水 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 37.75h， 生成 3-amino-1-(4-nitrophenyl)-propan-1-ol
  参考文献：
  名称：

  Nitroaryl Phosphoramides as Novel Prodrugs for E. coli Nitroreductase Activation in Enzyme Prodrug Therapy

  摘要：

  Cyclic and acyclic nitroaryl phosphoramide mustard analogues were activated by E. coli nitroreductase, an enzyme explored in GDEPT. The more active acyclic 4-nitrobenzyl phosphoramide mustard (7) showed 167 500x selective cytotoxicity toward nitroreductase-expressing V79 cells with an IC50 as low as 0.4 nM. This is about 100 x more active and 27x more selective than CB1954 (1). The superior activity was attributed to its better substrate activity (k(cat)/K-m 19x better than 1) and/or excellent cytotoxicity of phosphoramide mustard released.

  DOI：

  10.1021/jm034133h
• 作为产物：
  描述：

  1-methoxymethoxy-1-(4-nitrophenyl)-2-propene 在 硼烷四氢呋喃络合物 、 sodium hydroxide 、 双氧水 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 5.5h， 以78%的产率得到3-methoxymethoxy-3-(4-nitrophenyl)-propan-1-ol
  参考文献：
  名称：

  Nitroaryl phosphoramide compositions and methods for targeting and inhibiting undesirable cell growth or proliferation

  摘要：

  本发明涉及硝基芳基取代的磷酰胺前药化合物及其制备方法，用于靶向和抑制不良细胞生长或增殖。

  公开号：

  US20040214798A1

文献信息

• A Simple One-Pot Procedure for the Direct Conversion of Alcohols to Azides via Phosphate Activation
  作者：Chengzhi Yu、Bin Liu、Longqin Hu

  DOI：10.1021/ol0060376

  日期：2000.6.1

  A one-pot procedure was developed to prepare efficiently alkyl azides from alkanols using bis(2,4-dichlorophenyl) phosphate activation. 4-(Dimethylamino)pyridine was used as a base, and phosphorylpyridinium azide is believed to be the activating agent under this condition.

  开发了一锅法以使用双（2,4-二氯苯基）磷酸酯活化从烷醇有效制备烷基叠氮化物。使用4-（二甲基氨基）吡啶作为碱，在这种条件下，叠氮化磷酸吡啶被认为是活化剂。
• Nitroaryl phosphoramide compositions and methods for targeting and inhibiting undesirable cell growth or proliferation
  申请人：——

  公开号：US20040214798A1

  公开（公告）日：2004-10-28

  The present invention relates to nitroaryl-substituted phosphoramide prodrug compounds and methods of producing the same for use in targeting and inhibiting undesirable cell growth or proliferation.

  本发明涉及硝基芳基取代的磷酰胺前药化合物及其制备方法，用于靶向和抑制不良细胞生长或增殖。
• Nitroaryl Phosphoramides as Novel Prodrugs for <i>E. coli</i> Nitroreductase Activation in Enzyme Prodrug Therapy
  作者：Longqin Hu、Chengzhi Yu、Yongying Jiang、Jiye Han、Zhuorong Li、Patrick Browne、Paul R. Race、Richard J. Knox、Peter F. Searle、Eva I. Hyde

  DOI：10.1021/jm034133h

  日期：2003.11.1

  Cyclic and acyclic nitroaryl phosphoramide mustard analogues were activated by E. coli nitroreductase, an enzyme explored in GDEPT. The more active acyclic 4-nitrobenzyl phosphoramide mustard (7) showed 167 500x selective cytotoxicity toward nitroreductase-expressing V79 cells with an IC50 as low as 0.4 nM. This is about 100 x more active and 27x more selective than CB1954 (1). The superior activity was attributed to its better substrate activity (k(cat)/K-m 19x better than 1) and/or excellent cytotoxicity of phosphoramide mustard released.
• A modified procedure for the deprotection of methoxymethyl ether
  作者：Chengzhi Yu、Bin Liu、Longqin Hu

  DOI：10.1016/s0040-4039(99)02200-5

  日期：2000.2

  A new modified procedure using a combination of catechol boron bromide with acetic acid was developed to deprotect methoxymethyl group to form 1,3-diols and 1,3-aminoalcohols. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Design, Synthesis, and Biological Evaluation of Cyclic and Acyclic Nitrobenzylphosphoramide Mustards for <i>E. </i><i>c</i><i>oli </i>Nitroreductase Activation
  作者：Yongying Jiang、Jiye Han、Chengzhi Yu、Simon O. Vass、Peter F. Searle、Patrick Browne、Richard J. Knox、Longqin Hu

  DOI：10.1021/jm051246n

  日期：2006.7.1

  In efforts to obtain anticancer prodrugs for antibody-directed or gene-directed enzyme prodrug therapy using E. coli nitroreductase, a series of nitrobenzylphosphoramide mustards were designed and synthesized incorporating a strategically placed nitro group in a position para to the benzylic carbon for reductive activation. All analogues were good substrates of E. coli nitroreductase with half-lives between 2.9 and 11.9 min at pH 7.0 and 37 degrees C. Isomers of the 4-nitrophenylcyclophosphamide analogues 3 and 5 with a benzylic oxygen para to the nitro group showed potent selective cytotoxicity in nitroreductase (NTR) expressing cells, while analogues 4 and 6 with a benzylic nitrogen para to the nitro group showed little selective cytotoxicity despite their good substrate activity. These results suggest that good substrate activity and the benzylic oxygen are both required for reductive activation of 4-nitrophenylcyclophosphamide analogues by E. coli nitroreductase. Isomers of analogue 3 showed 23000-29000 x selective cytotoxicity toward NTR-expressing V79 cells with an IC50 as low as 27 nM. They are about as active as and 3-4x more selective than 5-aziridinyl-2,4-dinitrobenzamide (CB1954). The acyclic 4-nitrobenzylphosphoramide mustard ((+/-)-7) was found to be the most active and most selective compound for activation by NTR with 170000x selective cytotoxicity toward NTR-expressing V79 cells and an IC50 of 0.4 nM. Compound (+/-)-7 also exhibited good bystander effect compared to 5-aziridinyl-2,4-dinitrobenzamide. The low IC50, high selectivity, and good bystander effects of nitrobenzylphosphoramide mustards in NTR-expressing cells suggest that they could be used in combination with E. coli nitroreductase in enzyme prodrug therapy.