etoposide 4'-dimethylglycine 3''-hemiglutarate | 1220508-26-8

• 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 3''-hemiglutarate
• 英文别名: 5-[[(2R,4aR,6R,7R,8R,8aR)-6-[[(5S,5aR,8aR,9R)-9-[4-[2-(dimethylamino)acetyl]oxy-3,5-dimethoxyphenyl]-8-oxo-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[6,5-f][1,3]benzodioxol-5-yl]oxy]-7-hydroxy-2-methyl-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxin-8-yl]oxy]-5-oxopentanoic acid
• CAS: 1220508-26-8
• 化学式: C₃₈H₄₅NO₁₇
• 分子量: 787.772
• InChiKey: XIGYCAWAYPOOMI-CTLQCHHOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  56
• 可旋转键数：
  15
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  214
• 氢给体数：
  2
• 氢受体数：
  18

反应信息

• 作为产物：
  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