methyl 2-(2-methoxyethoxy)-4-nitrobenzoate | 304015-31-4

• 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: methyl 2-(2-methoxyethoxy)-4-nitrobenzoate
• 英文别名: 2-methoxyethoxy-4-nitro-benzoic acid methyl ester
• CAS: 304015-31-4
• 化学式: C₁₁H₁₃NO₆
• 分子量: 255.227
• InChiKey: JHTCIXRVRGUSPC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  90.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 2-(2-methoxyethoxy)-4-nitrobenzoate 在 二异丁基氢化铝 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 1.0h， 以91%的产率得到2-[2-(methoxy)ethoxy]-4-nitrobenzyl alcohol
  参考文献：
  名称：

  Structure−Activity Relationships for 4-Nitrobenzyl Carbamates of 5-Aminobenz[e]indoline Minor Groove Alkylating Agents as Prodrugs for GDEPT in Conjunction with E. coli Nitroreductase

  摘要：

  Twelve substituted 4-nitrobenzyl carbamate prodrugs of the 5-aminobenz[e]indoline class of DNA minor groove alkylating agents were prepared and tested as prodrugs for gene-directed enzyme prodrug therapy (GDEPT) using a two-electron nitroreductase (NTR) from E. coli B. The prodrugs and effectors were tested in a cell line panel comprising parental and transfected human (SKOV/Skov-NTRneo, WiDr/WiDr-NTRneo), Chinese hamster (V79(puro)/VN79-NTRpuro), and murine (EMT6/EMT6-NTRpuro) cell line pairs. In the human cell line pairs, several analogues bearing neutral methoxyethoxy-, 2-hydroxyethoxy-, or 3-hydroxypropoxy-substituted side chains were good substrates for NTR as measured by cytotoxicity ratios, with NTR-ve/NTR+ve ratios similar to the established NTR substrates CB1954 (an aziridinyl dinitrobenzamide) and the analogous bromomustard. Selectivity for NTR decreased with increasing side-chain size or the presence of a basic amine group. Low to modest selectivity was observed in the Chinese hamster-derived cell line pair; however, in the murine EMT6/EMT6-NTRpuro cell line pair, the above hydroxyalkoxy analogues again showed significant selectivity for NTR. The activity of the 2-hydroxyethoxy analogue was evaluated against NTR-expressing EMT6 tumors comprising ca. 10% NTR+ve cells at the time of tumor treatment. A small decrease in NTR+ve cells was observed after treatment, with a lesser effect against NTR-ve target cells, but these effects were not statistically significant and were much less than for the dinitrobenzamides. These results suggest that useful GDEPT prodrugs based on the 4-nitrobenzyl carbamate and 5-aminobenz[e]indoline motifs may be developed if optimization of pharmacokinetics can be addressed.

  DOI：

  10.1021/jm0205191
• 作为产物：
  描述：

  2-羟基-4-硝基苯甲酸甲酯 、 2-溴乙基甲基醚 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 以98%的产率得到methyl 2-(2-methoxyethoxy)-4-nitrobenzoate
  参考文献：
  名称：

  Structure−Activity Relationships for 4-Nitrobenzyl Carbamates of 5-Aminobenz[e]indoline Minor Groove Alkylating Agents as Prodrugs for GDEPT in Conjunction with E. coli Nitroreductase

  摘要：

  Twelve substituted 4-nitrobenzyl carbamate prodrugs of the 5-aminobenz[e]indoline class of DNA minor groove alkylating agents were prepared and tested as prodrugs for gene-directed enzyme prodrug therapy (GDEPT) using a two-electron nitroreductase (NTR) from E. coli B. The prodrugs and effectors were tested in a cell line panel comprising parental and transfected human (SKOV/Skov-NTRneo, WiDr/WiDr-NTRneo), Chinese hamster (V79(puro)/VN79-NTRpuro), and murine (EMT6/EMT6-NTRpuro) cell line pairs. In the human cell line pairs, several analogues bearing neutral methoxyethoxy-, 2-hydroxyethoxy-, or 3-hydroxypropoxy-substituted side chains were good substrates for NTR as measured by cytotoxicity ratios, with NTR-ve/NTR+ve ratios similar to the established NTR substrates CB1954 (an aziridinyl dinitrobenzamide) and the analogous bromomustard. Selectivity for NTR decreased with increasing side-chain size or the presence of a basic amine group. Low to modest selectivity was observed in the Chinese hamster-derived cell line pair; however, in the murine EMT6/EMT6-NTRpuro cell line pair, the above hydroxyalkoxy analogues again showed significant selectivity for NTR. The activity of the 2-hydroxyethoxy analogue was evaluated against NTR-expressing EMT6 tumors comprising ca. 10% NTR+ve cells at the time of tumor treatment. A small decrease in NTR+ve cells was observed after treatment, with a lesser effect against NTR-ve target cells, but these effects were not statistically significant and were much less than for the dinitrobenzamides. These results suggest that useful GDEPT prodrugs based on the 4-nitrobenzyl carbamate and 5-aminobenz[e]indoline motifs may be developed if optimization of pharmacokinetics can be addressed.

  DOI：

  10.1021/jm0205191

文献信息

• Radiohalogenated benzamide derivatives and their use in tumor diagnosis and tumor therapy
  申请人：Friebe Matthias

  公开号：US20050207972A1

  公开（公告）日：2005-09-22

  This invention relates to new radiohalogenated benzamide derivatives and their use in tumor diagnosis and tumor therapy. The radiohalogenated benzamide derivatives according to the invention exhibit novel and especially advantageous properties, in particular with respect to tumor concentration and retardation, liver concentration and blood accumulation. The radiation-therapy doses to be achieved in the tumor, compared to healthy body tissue, are advantageous for the compounds according to the invention.

  这项发明涉及新的放射性卤代苯甲酰胺衍生物及其在肿瘤诊断和肿瘤治疗中的应用。根据本发明，放射性卤代苯甲酰胺衍生物表现出新颖和特别有利的特性，特别是在肿瘤浓集和延迟、肝脏浓集和血液积聚方面。与健康身体组织相比，本发明的化合物在肿瘤中实现的放射治疗剂量具有优势。
• Radiohalogenated Benzamide Derivatives And Their Use In Tumor Diagnosis And Tumor Therapy
  申请人：Friebe Matthias

  公开号：US20090012090A1

  公开（公告）日：2009-01-08

  This invention relates to new radiohalogenated benzamide derivatives and their use in tumor diagnosis and tumor therapy. The radiohalogenated benzamide derivatives according to the invention exhibit novel and especially advantageous properties, in particular with respect to tumor concentration and retardation, liver concentration and blood accumulation. The radiation-therapy doses to be achieved in the tumor, compared to healthy body tissue, are advantageous for the compounds according to the invention.

  这项发明涉及新的放射性卤代苯甲酰胺衍生物及其在肿瘤诊断和肿瘤治疗中的应用。根据本发明，放射性卤代苯甲酰胺衍生物表现出新颖和特别有利的性质，特别是在肿瘤浓度和延迟、肝脏浓度和血液积累方面。与健康体组织相比，本发明中化合物在肿瘤中所需的放射治疗剂量具有优势。
• N-PROTECTED AMINES AND THEIR USE AS PRODRUGS
  申请人：CANCER RESEARCH CAMPAIGN TECHNOLOGY LIMITED

  公开号：EP1173414A1

  公开（公告）日：2002-01-23
• RADIOHALOGENATED BENZAMIDE DERIVATIVES AND THEIR USE IN TUMOR DIAGNOSIS AND TUMOR THERAPY
  申请人：Schering AG

  公开号：EP1722827A2

  公开（公告）日：2006-11-22
• US7427390B2
  申请人：——

  公开号：US7427390B2

  公开（公告）日：2008-09-23