O-{2-[(1,2,3-triazolyl)-4-(4-(N-maleimidomethyl)cyclohexane-1-carboxamidomethyl)]ethyl}-O'-[(N-diglycolyl-2-aminoethyl)-PAB-OCO-20-O-SN-38]heptaethyleneglycol trifluoroacetate | 1083198-48-4

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 喜树碱
• 英文名称: O-{2-[(1,2,3-triazolyl)-4-(4-(N-maleimidomethyl)cyclohexane-1-carboxamidomethyl)]ethyl}-O'-[(N-diglycolyl-2-aminoethyl)-PAB-OCO-20-O-SN-38]heptaethyleneglycol trifluoroacetate
• CAS: 1083198-48-4
• 化学式: C₂HF₃O₂*C₆₇H₈₅N₉O₂₁
• 分子量: 1466.48
• InChiKey: TUQYOTPKYFVZCK-MQMPSWLHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.19
• 重原子数：
  104.0
• 可旋转键数：
  42.0
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  392.71
• 氢给体数：
  5.0
• 氢受体数：
  27.0

反应信息

• 作为产物：
  描述：

  O-{2-[(1,2,3-triazolyl)-4-(4-(N-maleimidomethyl)cyclohexane-1-carboxamidomethyl)]ethyl}-O'-[(N-diglycolyl-2-aminoethyl)-PAB-OCO-20-O-SN-38-10-O-tert-butoxycarbonyl]heptaethyleneglycol 、 三氟乙酸 在 水 、 苯甲醚 作用下， 以 二氯甲烷 为溶剂， 反应 0.08h， 以75%的产率得到O-{2-[(1,2,3-triazolyl)-4-(4-(N-maleimidomethyl)cyclohexane-1-carboxamidomethyl)]ethyl}-O'-[(N-diglycolyl-2-aminoethyl)-PAB-OCO-20-O-SN-38]heptaethyleneglycol trifluoroacetate
  参考文献：
  名称：

  Antibody Conjugates of 7-Ethyl-10-hydroxycamptothecin (SN-38) for Targeted Cancer Chemotherapy

  摘要：

  CPT-11 is a clinically used cancer drug, and it is a prodrug of the potent topoisomerase I inhibitor, SN-38 (7-ethyl-10-hydroxycamptothecin). To bypass the need for the in vivo conversion of CPT-11 and increase the therapeutic index, bifunctional derivatives of SN-38 were prepared for use in anti body-based targeted therapy of cancer. The general synthetic scheme incorporated an acetylene-azide click cycloaddition step in the design, a short polyethylene glycol spacer for aqueous solubility, and a maleimide group conjugation. Conjugates of a humanized anti-CEACAM5 monoclonal antibody, hMN-14, prepared using, these SN-38 derivatives were evaluated in vitro for stability in buffer and human serum and for antigen-binding and cytotoxicity in a human colon adenocarcinoma cell line. Conjugates of hMN-14 and SN-38 derivatives 16 and 17 were found promising for further development.

  DOI：

  10.1021/jm800719t