4-acetamido-N-[2-[[5-[[3-[[5-[[4-[[2-[[3-[[5-[[2-[1-(chloromethyl)-5-hydroxy-1,2-dihydrobenzo[e]indole-3-carbonyl]-1H-indol-5-yl]carbamoyl]-1-methylpyrrol-3-yl]amino]-3-oxopropyl]carbamoyl]-1-methylimidazol-4-yl]amino]-4-oxobutyl]carbamoyl]-1-methylpyrrol-3-yl]amino]-3-oxopropyl]carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylimidazol-4-yl]-1-methylimidazole-2-carboxamide | 1361049-38-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: 4-acetamido-N-[2-[[5-[[3-[[5-[[4-[[2-[[3-[[5-[[2-[1-(chloromethyl)-5-hydroxy-1,2-dihydrobenzo[e]indole-3-carbonyl]-1H-indol-5-yl]carbamoyl]-1-methylpyrrol-3-yl]amino]-3-oxopropyl]carbamoyl]-1-methylimidazol-4-yl]amino]-4-oxobutyl]carbamoyl]-1-methylpyrrol-3-yl]amino]-3-oxopropyl]carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylimidazol-4-yl]-1-methylimidazole-2-carboxamide
• CAS: 1361049-38-8
• 化学式: C₆₇H₇₀ClN₂₁O₁₂
• 分子量: 1396.88
• InChiKey: ASIVHVBQIVIUGB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  101
• 可旋转键数：
  25
• 环数：
  11.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  416
• 氢给体数：
  12
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  NH2-indole-seco-1,2,9,9a-tetrahydrocyclopropa[1,2-c]benz[1,2-e]indol-4-one 、 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以14%的产率得到4-acetamido-N-[2-[[5-[[3-[[5-[[4-[[2-[[3-[[5-[[2-[1-(chloromethyl)-5-hydroxy-1,2-dihydrobenzo[e]indole-3-carbonyl]-1H-indol-5-yl]carbamoyl]-1-methylpyrrol-3-yl]amino]-3-oxopropyl]carbamoyl]-1-methylimidazol-4-yl]amino]-4-oxobutyl]carbamoyl]-1-methylpyrrol-3-yl]amino]-3-oxopropyl]carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylimidazol-4-yl]-1-methylimidazole-2-carboxamide
  参考文献：
  名称：

  Synthesis and Biological Properties of Highly Sequence-Specific-Alkylating N-Methylpyrrole–N-Methylimidazole Polyamide Conjugates

  摘要：

  Four new alkylating N-methylpyrrole-N-methylimidazole (PI) polyamide conjugates (1-4) with seven-base-pair (bp) recognition ability were synthesized. Evaluation of their DNA-alkylating activity clearly showed accurate alkylation at match site(s). The cytotconcities of conjugates 1-4 were determined against six human cancer cell lines, and the effect of these conjugates on the expression levels of the whole human genome in A549 cells were also investigated. A few genes among the top 20 genes were commonly downregulated by each conjugate, which reflects their sequence specificity. Conversely, many of the top 10 genes were commonly upregulated, which may have been caused by alkylation damage to DNA. Moreover, the antitumor activities of the PI polyamide conjugates 2 and 3 were investigated using nude mice transplanted with DU145 or A549. The intravenous administration of each liposomal conjugate in water yielded tumor-suppressing effects specifically toward DU145 cells and not A549 cells, which was pertinent to cytotoxicity.

  DOI：

  10.1021/jm201225z

文献信息

• Synthesis and Biological Properties of Highly Sequence-Specific-Alkylating <i>N</i>-Methylpyrrole–<i>N</i>-Methylimidazole Polyamide Conjugates
  作者：Gengo Kashiwazaki、Toshikazu Bando、Tomofumi Yoshidome、Seiji Masui、Toshiki Takagaki、Kaori Hashiya、Ganesh N. Pandian、Junichi Yasuoka、Kazunari Akiyoshi、Hiroshi Sugiyama

  DOI：10.1021/jm201225z

  日期：2012.3.8

  Four new alkylating N-methylpyrrole-N-methylimidazole (PI) polyamide conjugates (1-4) with seven-base-pair (bp) recognition ability were synthesized. Evaluation of their DNA-alkylating activity clearly showed accurate alkylation at match site(s). The cytotconcities of conjugates 1-4 were determined against six human cancer cell lines, and the effect of these conjugates on the expression levels of the whole human genome in A549 cells were also investigated. A few genes among the top 20 genes were commonly downregulated by each conjugate, which reflects their sequence specificity. Conversely, many of the top 10 genes were commonly upregulated, which may have been caused by alkylation damage to DNA. Moreover, the antitumor activities of the PI polyamide conjugates 2 and 3 were investigated using nude mice transplanted with DU145 or A549. The intravenous administration of each liposomal conjugate in water yielded tumor-suppressing effects specifically toward DU145 cells and not A549 cells, which was pertinent to cytotoxicity.