| 471905-83-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• CAS: 471905-83-6
• 化学式: C₅₇H₈₂N₈O₁₃
• 分子量: 1087.32
• InChiKey: LZLIOUFJCHKPNQ-PLSMQAEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  78.0
• 可旋转键数：
  24.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  311.78
• 氢给体数：
  9.0
• 氢受体数：
  14.0

反应信息

• 作为产物：
  描述：

  格尔德霉素 在 4-二甲氨基吡啶 作用下， 生成
  参考文献：
  名称：

  摘要：

  Purpose. To optimize the structure of geldanamycin (GDM) derivative moieties attached to N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers via an enzymatically degradable spacer.Methods HPMA copolymers containing different AR-GDM (AR=3-aminopropyl (AP), 6-aminohexyl (AH), and 3-amino-2-hydroxypropyl AP(OH)) were synthesized and characterized. Their cytotoxicity towards the A2780 human ovarian carcinoma cells was evaluated.Results The cytotoxic efficacy of HPMA copolymer-AR-GDM conjugates depended on the structure of AR-GDM. Particularly, HPMA copolymer-bound AH-GDM, which possessed the longest substituent at the 17-position, demonstrated the highest efficacy among the polymer-bound GDM derivatives; however the activity of free AH-GDM was lower than that of the other free AR-GDMs. The relative increase of the activity of macromolecular AH-GDM when compared to AP-GDM or AP(OH)-GDM correlated with the enhanced recognition of AH-GDM terminated oligopeptide side-chains by the active site of the lysosomal enzyme, cathepsin B. Drug stability and further stabilization upon binding to HPMA copolymer also contributed to the observed phenomena.Conclusions AH-GDM was found to be a suitable GDM derivative for the design of a drug delivery system based on HPMA copolymers and enzymatically-degradable spacers.

  DOI：

  10.1023/a:1014216712820