[5-(5-{2-[1-Chloromethyl-7-(3-dimethylamino-propylsulfamoyl)-5-nitro-1,2-dihydro-benzo[e]indole-3-carbonyl]-benzofuran-5-yl}-furan-2-yl)-benzofuran-2-yl]-(1-chloromethyl-7-(3-dimethylamino-propylsulfamoyl)-5-nitro-1,2-dihydro-benzo[e]indol-3-yl)-methanone | 1147721-43-4

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: [5-(5-{2-[1-Chloromethyl-7-(3-dimethylamino-propylsulfamoyl)-5-nitro-1,2-dihydro-benzo[e]indole-3-carbonyl]-benzofuran-5-yl}-furan-2-yl)-benzofuran-2-yl]-(1-chloromethyl-7-(3-dimethylamino-propylsulfamoyl)-5-nitro-1,2-dihydro-benzo[e]indol-3-yl)-methanone
• 英文别名: 1-(chloromethyl)-3-[5-[5-[2-[1-(chloromethyl)-7-[3-(dimethylamino)propylsulfamoyl]-5-nitro-1,2-dihydrobenzo[e]indole-3-carbonyl]-1-benzofuran-5-yl]furan-2-yl]-1-benzofuran-2-carbonyl]-N-[3-(dimethylamino)propyl]-5-nitro-1,2-dihydrobenzo[e]indole-7-sulfonamide
• CAS: 1147721-43-4
• 化学式: C₅₈H₅₄Cl₂N₈O₁₃S₂
• 分子量: 1206.15
• InChiKey: WKKUPILUDZKGNB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.5
• 重原子数：
  83
• 可旋转键数：
  18
• 环数：
  11.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  287
• 氢给体数：
  2
• 氢受体数：
  17

文献信息

• BIS-ALKYLATING AGENTS AND THEIR USE IN CANCER THERAPY
  申请人：Szekely Zoltan

  公开号：US20090118349A1

  公开（公告）日：2009-05-07

  The present invention relates to (i) conjugates comprising two DNA alkylating subunits linked by a moiety fitting to the minor groove of the DNA, (ii) to their preparation and (iii) to their use in cancer therapy. The alkylating subunits are especially cytotoxic under hypoxic conditions found in cancer cells. The compounds of the present invention and compositions thereof are useful in the treatment of cancer in a mammal, both alone or in a combination with other anti-cancer agents (e.g. checkpoint abrogators) and/or radiation. They may also be used as cytotoxic units for gene-directed enzyme-prodrug therapy (GDEPT) and antibody-directed enzyme-prodrug therapy (ADEPT). The present invention provides the compounds of Formula (I), Formula (II) and Formula (III): for treating cancer in a mammal.

  本发明涉及（i）由适合于DNA小沟的基团连接的两个DNA烷基化亚基组成的共轭物，（ii）它们的制备和（iii）它们在癌症治疗中的应用。烷基化亚基在癌细胞中发现的低氧条件下特别具有细胞毒性。本发明的化合物及其组合物在哺乳动物中治疗癌症方面具有用途，可以单独使用或与其他抗癌药物（例如检查点阻断剂）和/或放射线结合使用。它们还可以用作基因定向酶-前药疗法（GDEPT）和抗体定向酶-前药疗法（ADEPT）的细胞毒性单位。本发明提供了式（I）、式（II）和式（III）的化合物，用于哺乳动物中治疗癌症。