etoposide 4'-dimethylglycine | 1220508-24-6

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 木脂素内酯
• 英文名称: etoposide 4'-dimethylglycine
• 英文别名: [4-[(5S,5aR,8aR,9R)-5-[[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-methyl-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy]-8-oxo-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-9-yl]-2,6-dimethoxyphenyl] 2-(dimethylamino)acetate
• CAS: 1220508-24-6
• 化学式: C₃₃H₃₉NO₁₄
• 分子量: 673.671
• InChiKey: XKBVMJXPJPTGHS-AAGORTAFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  48
• 可旋转键数：
  9
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  170
• 氢给体数：
  2
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  戊二酸酐 、 etoposide 4'-dimethylglycine 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 以40%的产率得到etoposide 4'-dimethylglycine 2''-hemiglutarate
  参考文献：
  名称：

  New Angiopep-Modified Doxorubicin (ANG1007) and Etoposide (ANG1009) Chemotherapeutics With Increased Brain Penetration

  摘要：

  This report describes the synthesis and preliminary biological characterization of 2 (ANG1007) and 3 (ANG1009), two new chemical entities under development for the treatment of primary and secondary brain cancers. 2 consists of three doxorubicin molecules conjugated to Angiopep-2, a 19-mer peptide that crosses the blood brain barrier (BBB) by an LRP-1 receptor-mediated transcytosis mechanism. 3 has a similar structure, with the exception that three etoposide moieties are conjugated to Angiopep-2. Both agents killed cancer cell lines in vitro with similar IC50 values and with apparently similar cytotoxic mechanisms as unconjugated doxorubicin and etoposide. 2 and 3 exhibited dramatically higher BBB influx rate constants than unconjugated doxorubicin and etoposide and pooled within brain parenchymal tissue. Passage through the BBB was similar in Mdr1a (-/-) and wild type mice. These results provide further evidence of the potential of this drug development platform in the isolation of novel therapeutics with increased brain penetration.

  DOI：

  10.1021/jm9016637
• 作为产物：
  描述：

  (二甲基氨基)乙酰氯 、 依托泊苷 在 4-二甲氨基吡啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.83h， 以67%的产率得到etoposide 4'-dimethylglycine
  参考文献：
  名称：

  New Angiopep-Modified Doxorubicin (ANG1007) and Etoposide (ANG1009) Chemotherapeutics With Increased Brain Penetration

  摘要：

  This report describes the synthesis and preliminary biological characterization of 2 (ANG1007) and 3 (ANG1009), two new chemical entities under development for the treatment of primary and secondary brain cancers. 2 consists of three doxorubicin molecules conjugated to Angiopep-2, a 19-mer peptide that crosses the blood brain barrier (BBB) by an LRP-1 receptor-mediated transcytosis mechanism. 3 has a similar structure, with the exception that three etoposide moieties are conjugated to Angiopep-2. Both agents killed cancer cell lines in vitro with similar IC50 values and with apparently similar cytotoxic mechanisms as unconjugated doxorubicin and etoposide. 2 and 3 exhibited dramatically higher BBB influx rate constants than unconjugated doxorubicin and etoposide and pooled within brain parenchymal tissue. Passage through the BBB was similar in Mdr1a (-/-) and wild type mice. These results provide further evidence of the potential of this drug development platform in the isolation of novel therapeutics with increased brain penetration.

  DOI：

  10.1021/jm9016637

文献信息

• ETOPOSIDE AND DOXORUBICIN CONJUGATES FOR DRUG DELIVERY
  申请人：Angiochem Inc.

  公开号：US20150038429A1

  公开（公告）日：2015-02-05

  The invention relates to improvements in the field of drug delivery. More particularly, the invention relates to polypeptides having a hydrolyzable covalent bond to a therapeutic agent that includes, etoposide, etoposide 4′-dimethylglycine or doxorubicin. These polypeptide conjugates can be used as vectors to transport the podophyllotoxin derivative across the blood brain barrier (BBB) or into particular cell types such as ovary, liver, lung, or kidney. The invention also relates to pharmaceutical compositions that include the compounds of the invention and to uses thereof in methods of treatment.
• New Angiopep-Modified Doxorubicin (ANG1007) and Etoposide (ANG1009) Chemotherapeutics With Increased Brain Penetration
  作者：Christian Ché、Gaoqiang Yang、Carine Thiot、Marie-Claude Lacoste、Jean-Christophe Currie、Michel Demeule、Anthony Régina、Richard Béliveau、Jean-Paul Castaigne

  DOI：10.1021/jm9016637

  日期：2010.4.8

  This report describes the synthesis and preliminary biological characterization of 2 (ANG1007) and 3 (ANG1009), two new chemical entities under development for the treatment of primary and secondary brain cancers. 2 consists of three doxorubicin molecules conjugated to Angiopep-2, a 19-mer peptide that crosses the blood brain barrier (BBB) by an LRP-1 receptor-mediated transcytosis mechanism. 3 has a similar structure, with the exception that three etoposide moieties are conjugated to Angiopep-2. Both agents killed cancer cell lines in vitro with similar IC50 values and with apparently similar cytotoxic mechanisms as unconjugated doxorubicin and etoposide. 2 and 3 exhibited dramatically higher BBB influx rate constants than unconjugated doxorubicin and etoposide and pooled within brain parenchymal tissue. Passage through the BBB was similar in Mdr1a (-/-) and wild type mice. These results provide further evidence of the potential of this drug development platform in the isolation of novel therapeutics with increased brain penetration.