[(19S)-10,19-diethyl-7-hydroxy-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-19-yl] 2-[[4-[[(2S)-2-[[(2S)-2-[[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[4-[[[4-[(2,5-dioxopyrrol-1-yl)methyl]cyclohexanecarbonyl]amino]methyl]triazol-1-yl]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethylamino]-2-oxoethoxy]acetyl]amino]-3-phenylpropanoyl]amino]-6-[[(4-methoxyphenyl)-diphenylmethyl]amino]hexanoyl]amino]phenyl]methoxycarbonylamino]acetate | 1084888-85-6

• 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: [(19S)-10,19-diethyl-7-hydroxy-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-19-yl] 2-[[4-[[(2S)-2-[[(2S)-2-[[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[4-[[[4-[(2,5-dioxopyrrol-1-yl)methyl]cyclohexanecarbonyl]amino]methyl]triazol-1-yl]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethylamino]-2-oxoethoxy]acetyl]amino]-3-phenylpropanoyl]amino]-6-[[(4-methoxyphenyl)-diphenylmethyl]amino]hexanoyl]amino]phenyl]methoxycarbonylamino]acetate
• CAS: 1084888-85-6
• 化学式: C₁₀₄H₁₂₅N₁₃O₂₅
• 分子量: 1957.21
• InChiKey: FCTNUWHRURMWGT-UOZBKXISSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  142
• 可旋转键数：
  62
• 环数：
  13.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  462
• 氢给体数：
  8
• 氢受体数：
  29

反应信息

• 作为反应物：
  描述：

  [(19S)-10,19-diethyl-7-hydroxy-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-19-yl] 2-[[4-[[(2S)-2-[[(2S)-2-[[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[4-[[[4-[(2,5-dioxopyrrol-1-yl)methyl]cyclohexanecarbonyl]amino]methyl]triazol-1-yl]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethylamino]-2-oxoethoxy]acetyl]amino]-3-phenylpropanoyl]amino]-6-[[(4-methoxyphenyl)-diphenylmethyl]amino]hexanoyl]amino]phenyl]methoxycarbonylamino]acetate 在 水 、 苯甲醚 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以90%的产率得到O-{2-[(1,2,3-triazolyl)-4-[4-(N-maleimidomethyl)cyclohexane-1-carboxamidomethyl]]ethyl}-O'-[(N-diglycolyl-2-aminoethyl)-Phe-Lys-PAB-OCO-Gly-20-O-SN-38]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：

  O-(2-azidoethyl)-O'-[(N-diglycolyl-2-aminoethyl)-Phe-Lys(MMT)-PAB-OCO-Gly-20-O-SN-38]heptaethyleneglycol 、 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 在 copper(I) bromide 作用下， 以 水 、 二甲基亚砜 为溶剂， 反应 1.0h， 以76%的产率得到[(19S)-10,19-diethyl-7-hydroxy-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-19-yl] 2-[[4-[[(2S)-2-[[(2S)-2-[[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[4-[[[4-[(2,5-dioxopyrrol-1-yl)methyl]cyclohexanecarbonyl]amino]methyl]triazol-1-yl]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethylamino]-2-oxoethoxy]acetyl]amino]-3-phenylpropanoyl]amino]-6-[[(4-methoxyphenyl)-diphenylmethyl]amino]hexanoyl]amino]phenyl]methoxycarbonylamino]acetate
  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