O-(2-azidoethyl)-O'-[(N-diglycolyl-2-aminoethyl)-PAB-OCO-20-O-SN-38-10-O-tert-butoxycarbonyl]heptaethyleneglycol | 1036847-93-4

• 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-azidoethyl)-O'-[(N-diglycolyl-2-aminoethyl)-PAB-OCO-20-O-SN-38-10-O-tert-butoxycarbonyl]heptaethyleneglycol
• 英文别名: [(19S)-19-[[4-[[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-(2-azidoethoxy)ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethylamino]-2-oxoethoxy]acetyl]amino]phenyl]methoxycarbonyloxy]-10,19-diethyl-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaen-7-yl] tert-butyl carbonate
• CAS: 1036847-93-4
• 化学式: C₅₇H₇₅N₇O₂₀
• 分子量: 1178.26
• InChiKey: PBSRFPXTEDEUMH-SMWREMLRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  84
• 可旋转键数：
  43
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  286
• 氢给体数：
  2
• 氢受体数：
  23

反应信息

• 作为反应物：
  描述：

  4-((2,5-二氧代-2,5-二氢-1H-吡咯-1-基)甲基)-N-(丙-2-炔-1-基)环己烷甲 、 O-(2-azidoethyl)-O'-[(N-diglycolyl-2-aminoethyl)-PAB-OCO-20-O-SN-38-10-O-tert-butoxycarbonyl]heptaethyleneglycol 在 copper(I) bromide 作用下， 以 水 、 二甲基亚砜 为溶剂， 反应 0.67h， 以84%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-38-10-O-tert-butoxycarbonyl]heptaethyleneglycol
  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
• 作为产物：
  描述：

  tert-butyl [(19S)-19-chlorocarbonyloxy-10,19-diethyl-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaen-7-yl]carbonate 、 O-(2-azidoethyl)-O'-[(N-diglycolyl-2-aminoethyl)-PAB-OH]heptaethyleneglycol 以 二氯甲烷 为溶剂， 以0.14 g的产率得到O-(2-azidoethyl)-O'-[(N-diglycolyl-2-aminoethyl)-PAB-OCO-20-O-SN-38-10-O-tert-butoxycarbonyl]heptaethyleneglycol
  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