phenyl 2-(2-((1-azido-13-oxo-3,6,9-trioxa-12-azaheptadecan-16-yl)disulfaneyl)phenyl)acetate | 1613697-63-4

• 分子结构分类: 有机化合物 - 苯类化合物
• 英文名称: phenyl 2-(2-((1-azido-13-oxo-3,6,9-trioxa-12-azaheptadecan-16-yl)disulfaneyl)phenyl)acetate
• CAS: 1613697-63-4
• 化学式: C₂₇H₃₆N₄O₆S₂
• 分子量: 576.738
• InChiKey: SCABRALHQBCCIO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.22
• 重原子数：
  39.0
• 可旋转键数：
  21.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  131.85
• 氢给体数：
  1.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  phenyl 2-(2-((1-azido-13-oxo-3,6,9-trioxa-12-azaheptadecan-16-yl)disulfaneyl)phenyl)acetate 、 [(1S,2S,3R,4S,7R,9S,10S,12R,15S)-15-[(2R,3S)-2-[2-[2-[[5-[2-[[4-[2-[2-[2-[2-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]ethoxy]ethoxy]ethoxy]ethylamino]-6-(prop-2-ynylamino)-1,3,5-triazin-2-yl]amino]ethylamino]-5-oxopentan-2-yl]disulfanyl]phenyl]acetyl]oxy-5-methyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]hex-4-enoyl]oxy-4-acetyloxy-12-(cyclopropanecarbonyloxy)-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate 在 copper(ll) sulfate pentahydrate 、 维生素 C 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 15.0h， 以79%的产率得到[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-15-[(2R,3S)-2-[2-[2-[[5-[2-[[4-[2-[2-[2-[2-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]ethoxy]ethoxy]ethoxy]ethylamino]-6-[[1-[2-[2-[2-[2-[4-[[2-(2-oxo-2-phenoxyethyl)phenyl]disulfanyl]pentanoylamino]ethoxy]ethoxy]ethoxy]ethyl]triazol-4-yl]methylamino]-1,3,5-triazin-2-yl]amino]ethylamino]-5-oxopentan-2-yl]disulfanyl]phenyl]acetyl]oxy-5-methyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]hex-4-enoyl]oxy-4-acetyloxy-12-(cyclopropanecarbonyloxy)-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.03,10.04,7]heptadec-13-en-2-yl] benzoate
  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：

  4-(2-pyridyldithio)-pentanoic acid 在 吡啶 、 4-二甲氨基吡啶 、 氢氟酸 、 三乙胺 、 N,N'-二异丙基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 50.0h， 生成 phenyl 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