20-[Aloc-D-Ala-Phe-Lys(Aloc)-p-aminobenzyl oxycarbonyl]-camptothecin

• 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
• 英文名称: 20-[Aloc-D-Ala-Phe-Lys(Aloc)-p-aminobenzyl oxycarbonyl]-camptothecin
• 英文别名: [(19S)-19-ethyl-14,18-dioxo-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4,6,8,10,15(20)-heptaen-19-yl] [4-[[(2S)-2-[[(2S)-3-phenyl-2-[[(2R)-2-(prop-2-enoxycarbonylamino)propanoyl]amino]propanoyl]amino]-6-(prop-2-enoxycarbonylamino)hexanoyl]amino]phenyl]methyl carbonate
• 化学式: C₅₄H₅₇N₇O₁₃
• 分子量: 1012.09
• InChiKey: JQWLVJXLCVJGOG-KQVHTCERSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  74
• 可旋转键数：
  26
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  259
• 氢给体数：
  5
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  喜树碱 、 Aloc-D-Ala-Phe-Lys(Aloc)-p-aminobenzyl oxycarbonyl p-nitrophenyl carbonate 在 4-二甲氨基吡啶 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 96.0h， 以16%的产率得到20-[Aloc-D-Ala-Phe-Lys(Aloc)-p-aminobenzyl oxycarbonyl]-camptothecin
  参考文献：
  名称：

  Novel 20-Carbonate Linked Prodrugs of Camptothecin and 9-Aminocamptothecin Designed for Activation by Tumour-Associated Plasmin

  摘要：

  The first prodrugs of camptothecin and 9-aminocamptothecin that are activated by the tumour-associated protease plasmin are reported. The tripartate prodrugs consist of a tripeptide sequence recognised by plasmin, which is linked to the 20-hydroxyl group of the camptothecins via a 1,6-elimination spacer. After selective N-protection of 9-aminocamptothecin with an Aloc group, the promoiety (tripeptide-spacer conjugate) was linked to camptothecin or 9-Aloc-9-aminocamptothecin via a 20-carbonate linkage by reacting parent drugs with the p-nitrophenyl carbonate activated promoiety in the presence of DMAP. Both prodrugs showed to be stable in buffer solution and both parent drugs were released upon incubation in the presence of plasmin. Furthermore, the prodrugs showed an average 10-fold decreased cytotoxicity with respect to their parent drugs upon incubation in seven human tumour cell lines. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00388-8

文献信息

• Novel 20-Carbonate Linked Prodrugs of Camptothecin and 9-Aminocamptothecin Designed for Activation by Tumour-Associated Plasmin
  作者：Franciscus M.H de Groot、Guuske F Busscher、René W.M Aben、Hans W Scheeren

  DOI：10.1016/s0960-894x(02)00388-8

  日期：2002.9

  The first prodrugs of camptothecin and 9-aminocamptothecin that are activated by the tumour-associated protease plasmin are reported. The tripartate prodrugs consist of a tripeptide sequence recognised by plasmin, which is linked to the 20-hydroxyl group of the camptothecins via a 1,6-elimination spacer. After selective N-protection of 9-aminocamptothecin with an Aloc group, the promoiety (tripeptide-spacer conjugate) was linked to camptothecin or 9-Aloc-9-aminocamptothecin via a 20-carbonate linkage by reacting parent drugs with the p-nitrophenyl carbonate activated promoiety in the presence of DMAP. Both prodrugs showed to be stable in buffer solution and both parent drugs were released upon incubation in the presence of plasmin. Furthermore, the prodrugs showed an average 10-fold decreased cytotoxicity with respect to their parent drugs upon incubation in seven human tumour cell lines. (C) 2002 Elsevier Science Ltd. All rights reserved.