| 1613697-59-8

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 喜树碱
• CAS: 1613697-59-8
• 化学式: C₃₃H₃₀N₂O₇S₂
• 分子量: 630.742
• InChiKey: BRXTWWAGPIZSSF-NDYPJNEKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.87
• 重原子数：
  44.0
• 可旋转键数：
  10.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  124.79
• 氢给体数：
  1.0
• 氢受体数：
  10.0

反应信息

• 作为反应物：
  描述：

  、 1-氨基-11-叠氮-3,6,9-三氧杂十一烷 在 N,N'-二异丙基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以71%的产率得到(S)-4-ethyl-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-4-yl 2-(2-((1-azido-13-oxo-3,6,9-trioxa-12-azaheptadecan-16-yl)disulfaneyl)phenyl)acetate
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluations of Tumor-Targeting Dual-Warhead Conjugates for a Taxoid–Camptothecin Combination Chemotherapy

  摘要：

  Novel tumor-targeting dual-warhead conjugates, 2 (DW-1) and 3 (DW-2), which consist of a next-generation taxoid, 1 (SB-T-1214), and camptothecin as two warheads, self-immolative disulfide linkers for drug release, biotin as the tumor-targeting moiety, and 1,3,5-triazine as the tripod splitter module, were designed and synthesized. The potency of 2 was evaluated against MX-1, MCF-7, ID8, L1210FR (BR+, biotin receptor overexpressed) and WI38 (BR-, normal) cell lines in the absence and presence of glutathione (GSH), which is an endogenous thiol that triggers drug release inside the cancer cells. With the GSH and resuspension protocol, 2 exhibited IC50 values of 3.22-9.80 nM against all BR+ cancer cell lines, and 705 nM against WI38. Thus, there was a two orders of magnitude higher selectivity to cancer cells. Also, a clear cooperative effect was observed for the taxoid-camptothecin combination when two drugs were delivered to the cancer cells specifically in the form of a dual-warhead conjugate.

  DOI：

  10.1021/jm500631u
• 作为产物：
  描述：

  triisopropylsilyl 4-((2-(2-(((S)-4-ethyl-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-4-yl)oxy)-2-oxoethyl)phenyl)disulfaneyl)pentanoate 在 吡啶 、 氢氟酸 作用下， 以 乙腈 为溶剂， 反应 5.0h， 以85%的产率得到
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluations of Tumor-Targeting Dual-Warhead Conjugates for a Taxoid–Camptothecin Combination Chemotherapy

  摘要：

  Novel tumor-targeting dual-warhead conjugates, 2 (DW-1) and 3 (DW-2), which consist of a next-generation taxoid, 1 (SB-T-1214), and camptothecin as two warheads, self-immolative disulfide linkers for drug release, biotin as the tumor-targeting moiety, and 1,3,5-triazine as the tripod splitter module, were designed and synthesized. The potency of 2 was evaluated against MX-1, MCF-7, ID8, L1210FR (BR+, biotin receptor overexpressed) and WI38 (BR-, normal) cell lines in the absence and presence of glutathione (GSH), which is an endogenous thiol that triggers drug release inside the cancer cells. With the GSH and resuspension protocol, 2 exhibited IC50 values of 3.22-9.80 nM against all BR+ cancer cell lines, and 705 nM against WI38. Thus, there was a two orders of magnitude higher selectivity to cancer cells. Also, a clear cooperative effect was observed for the taxoid-camptothecin combination when two drugs were delivered to the cancer cells specifically in the form of a dual-warhead conjugate.

  DOI：

  10.1021/jm500631u