(S)-ethyl 4-(4-(4-(4-((7-methoxy-5-oxo-2,3,5,11a-tetrahydro-1Hpyrrolo[2,1-c][1,4]benzodiazepin-8-yl)oxy)butanamido)phenyl)-1-methyl-1H-pyrrole-2-carboxamido)-1-methyl-1H-imidazole-2-carboxylate | 1428305-87-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: (S)-ethyl 4-(4-(4-(4-((7-methoxy-5-oxo-2,3,5,11a-tetrahydro-1Hpyrrolo[2,1-c][1,4]benzodiazepin-8-yl)oxy)butanamido)phenyl)-1-methyl-1H-pyrrole-2-carboxamido)-1-methyl-1H-imidazole-2-carboxylate
• 英文别名: (S)-ethyl 4-(4-(4-(4-(7-methoxy-5-oxo-2,3,5,11a-tetrahydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-8-yloxy)butanamido)phenyl)-1-methyl-1H-pyrrole-2-carboxamido)-1-methyl-1H-imidazole-2-carboxylate；ethyl 4-[[4-[4-[4-[[(6aS)-2-methoxy-11-oxo-6a,7,8,9-tetrahydropyrrolo[2,1-c][1,4]benzodiazepin-3-yl]oxy]butanoylamino]phenyl]-1-methylpyrrole-2-carbonyl]amino]-1-methylimidazole-2-carboxylate
• CAS: 1428305-87-6
• 化学式: C₃₆H₃₉N₇O₇
• 分子量: 681.748
• InChiKey: SVTPGRBHRQOEOO-VWLOTQADSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  50
• 可旋转键数：
  13
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  158
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  在 四氢吡咯 、 四(三苯基膦)钯 、 三苯基膦 作用下， 反应 0.5h， 生成 (S)-ethyl 4-(4-(4-(4-((7-methoxy-5-oxo-2,3,5,11a-tetrahydro-1Hpyrrolo[2,1-c][1,4]benzodiazepin-8-yl)oxy)butanamido)phenyl)-1-methyl-1H-pyrrole-2-carboxamido)-1-methyl-1H-imidazole-2-carboxylate
  参考文献：
  名称：

  GC-Targeted C8-Linked Pyrrolobenzodiazepine–Biaryl Conjugates with Femtomolar in Vitro Cytotoxicity and in Vivo Antitumor Activity in Mouse Models

  摘要：

  DNA binding 4-(1-methyl-1H-pyrrol-3-yl)-benzenamine (MPB) building blocks have been developed that span two DNA base pairs with a strong preference for GC-rich DNA. They have been conjugated to a pyrrolo[2,1-c][1,4]benzodiazepine (PBD) molecule to produce C8-linked PBD MPB hybrids that can stabilize GC-rich DNA by up to 13-fold compared to AT-rich DNA. Some have subpicomolar IC50 values in human tumor cell lines and in primary chronic lymphocytic leukemia cells, while being up to 6 orders less cytotoxic in the non-tumor cell line WI38, suggesting that key DNA sequences may be relevant targets in these ultrasensitive cancer cell lines. One conjugate, 7h (KMR-28-39), which has femtomolar activity in the breast cancer cell line MDA-MB-231, has significant dose-dependent antitumor activity in MDA-MB-231 (breast) and MIA PaCa-2 (pancreatic) human tumor xenograft mouse models with insignificant toxicity at therapeutic doses. Preliminary studies suggest that 7h may sterically inhibit interaction of the transcription factor NF-kappa B with its cognate DNA binding sequence.

  DOI：

  10.1021/jm301882a