4-acetamido-N-[2-[[5-[[2-[[3-[[5-[[2-[[4-[[5-[[2-[[5-[[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-methylpyrrol-3-yl]carbamoyl]-1-methylimidazol-4-yl]carbamoyl]-1-methylpyrrol-3-yl]amino]-4-oxobutyl]carbamoyl]-1-methylimidazol-4-yl]carbamoyl]-1-methylpyrrol-3-yl]amino]-3-oxopropyl]carbamoyl]-1-methylimidazol-4-yl]carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylimidazol-4-yl]-1-methylimidazole-2-carboxamide | 1609185-37-6

• 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-[[2-[[3-[[5-[[2-[[4-[[5-[[2-[[5-[[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-methylpyrrol-3-yl]carbamoyl]-1-methylimidazol-4-yl]carbamoyl]-1-methylpyrrol-3-yl]amino]-4-oxobutyl]carbamoyl]-1-methylimidazol-4-yl]carbamoyl]-1-methylpyrrol-3-yl]amino]-3-oxopropyl]carbamoyl]-1-methylimidazol-4-yl]carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylimidazol-4-yl]-1-methylimidazole-2-carboxamide
• CAS: 1609185-37-6
• 化学式: C₈₉H₉₂ClN₃₁O₁₆
• 分子量: 1887.36
• InChiKey: HGLABUCOTPNCBJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  137
• 可旋转键数：
  33
• 环数：
  15.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  578
• 氢给体数：
  16
• 氢受体数：
  21

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 、 以 N,N-二甲基甲酰胺 为溶剂， 生成 4-acetamido-N-[2-[[5-[[2-[[3-[[5-[[2-[[4-[[5-[[2-[[5-[[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-methylpyrrol-3-yl]carbamoyl]-1-methylimidazol-4-yl]carbamoyl]-1-methylpyrrol-3-yl]amino]-4-oxobutyl]carbamoyl]-1-methylimidazol-4-yl]carbamoyl]-1-methylpyrrol-3-yl]amino]-3-oxopropyl]carbamoyl]-1-methylimidazol-4-yl]carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylimidazol-4-yl]-1-methylimidazole-2-carboxamide
  参考文献：
  名称：

  靶向吡咯-咪唑聚酰胺seco-CBI共轭物的Kras密码子13突变的序列特异性DNA烷基化反应。

  摘要：

  发夹Ñ -methylpyrrole- Ñ甲基咪唑聚酰胺开环-CBI缀合物2 - 6被设计为合成通过Fmoc固相合成，以及对所述K-ras的DNA烷基化的活动密码子13突变进行了比较由高分辨率变性凝胶电泳与225碱基对（bp）DNA片段。缀合物5对Kras密码子13突变位点具有高反应活性，烷基化发生在序列5'-ACGTCACC A -3 '（位点2）的A处，包括针对野生型5'-ACG C的次要1 bp-错配烷基化CACC A- 3'（站点3）。共轭6，不同于共轭5通过将一个Py单元换成β单元显示出高选择性，但仅使5'-ACGTCACC A -3 '的A弱烷基化（位点2）。发夹式聚酰胺seco- CBI共轭物5因此根据Dervan的配对规则烷基化，并具有配对识别，其中β/β对靶向T–A和A–T对。SPR和计算机最小化模型表明，5个发夹构象以高亲和力与靶序列结合，从而实现了有效的DNA烷基化。

  DOI：

  10.1002/chem.201303295

文献信息

• Alkylating agent for alkylating target with driver oncogene mutation
  申请人：CHIBA PREFECTURE

  公开号：US10350300B2

  公开（公告）日：2019-07-16

  The present invention provides a novel alkylating agent specifically binding to the genetic mutation site of a driver oncogene. There are provided are a complex formed by binding an alkylating agent to a pyrrole imidazole polyamide specifically binding to the genetic mutation site of a driver oncogene, a driver oncogene mutation-specific alkylating agent comprising the aforementioned complex, and a pharmaceutical composition comprising the aforementioned complex.

  本发明提供了一种新型烷化剂，可与驱动癌基因的基因突变位点特异性结合。本发明提供了一种通过烷化剂与吡咯咪唑聚酰胺结合形成的复合物，该复合物特异性地与驱动癌基因的基因突变位点结合；一种包含上述复合物的驱动癌基因突变特异性烷化剂；以及一种包含上述复合物的药物组合物。
• NOVEL ALKYLATING AGENT FOR ALKYLATING TARGET WITH DRIVER ONCOGENE MUTATION
  申请人：Chiba Prefecture

  公开号：US20190290773A1

  公开（公告）日：2019-09-26

  The present invention provides a novel alkylating agent specifically binding to the genetic mutation site of a driver oncogene. There are provided are a complex formed by binding an alkylating agent to a pyrrole imidazole polyamide specifically binding to the genetic mutation site of a driver oncogene, a driver oncogene mutation-specific alkylating agent comprising the aforementioned complex, and a pharmaceutical composition comprising the aforementioned complex.