2,9-dimethyl-1,2-dihydroellipticine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2,9-dimethyl-1,2-dihydroellipticine
• 英文别名: 6H-Pyrido[4, 1,2-dihydro-2,5,9,11-tetra-methyl-；2,5,9,11-tetramethyl-1,6-dihydropyrido[4,3-b]carbazole
• 化学式: C₁₉H₂₀N₂
• 分子量: 276.381
• InChiKey: LOCXAALEVBWMBX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  21
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  19
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  2,9-dimethylellipticinium acetate 在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 反应 18.0h， 以83%的产率得到2,9-dimethyl-1,2-dihydroellipticine
  参考文献：
  名称：

  Design and Synthesis of Ellipticinium Salts and 1,2-Dihydroellipticines with High Selectivities against Human CNS Cancers in vitro

  摘要：

  9-Methoxy-2-methylellipticinium acetate (6), along with the 9-methyl and 9-chloro derivatives (7, and 8, respectively) have shown remarkable selectivities in vitro against the NCI human CNS cancer subpanel. In order to target these types of compounds to the CNS in vivo, a series of 1,2-dihydroellipticines was synthesized. 9-Methoxy-2-methyl-1,2-dihydroellipticine (9) retained the potency and selectivity of the parent compound 6 but was unstable toward oxidation to 6. In order to improve the stability of 9, it was converted to the vinylogous amide 33 by introduction of a formyl group in the 4-position. Compound 33 proved to be much more stable than 9, but it was also less potent than 9 by about 1 order of magnitude, and it was less selective for the CNS subpanel than 9. To overcome the limited water solubilities of the ellipticines and dihydroellipticines, several ellipticine analogues incorporating polar groups on the N-2 nitrogen were prepared. The 2-(methoxymethyl)ellipticinium salts 24 and 25, as well as the (methylthio)methyl congener 26, were relatively potent anticancer agents which displayed cytotoxicity selectivity profiles similar to compound 6. The cytotoxic dihydroellipticines 9 and 10 exhibited potencies approaching that of ellipticine itself in facilitating the formation of a ''cleavable complex'', while the least cytotoxic ellipticine derivatives exhibited no cleavage above background.

  DOI：

  10.1021/jm00040a011

文献信息

• US5272146A
  申请人：——

  公开号：US5272146A

  公开（公告）日：1993-12-21
• US5441941A
  申请人：——

  公开号：US5441941A

  公开（公告）日：1995-08-15
• Design and Synthesis of Ellipticinium Salts and 1,2-Dihydroellipticines with High Selectivities against Human CNS Cancers in vitro
  作者：Jurjus Jurayj、Rudiger D. Haugwitz、Ravi K. Varma、Kenneth D. Paull、John F. Barrett、Mark Cushman

  DOI：10.1021/jm00040a011

  日期：1994.7

  9-Methoxy-2-methylellipticinium acetate (6), along with the 9-methyl and 9-chloro derivatives (7, and 8, respectively) have shown remarkable selectivities in vitro against the NCI human CNS cancer subpanel. In order to target these types of compounds to the CNS in vivo, a series of 1,2-dihydroellipticines was synthesized. 9-Methoxy-2-methyl-1,2-dihydroellipticine (9) retained the potency and selectivity of the parent compound 6 but was unstable toward oxidation to 6. In order to improve the stability of 9, it was converted to the vinylogous amide 33 by introduction of a formyl group in the 4-position. Compound 33 proved to be much more stable than 9, but it was also less potent than 9 by about 1 order of magnitude, and it was less selective for the CNS subpanel than 9. To overcome the limited water solubilities of the ellipticines and dihydroellipticines, several ellipticine analogues incorporating polar groups on the N-2 nitrogen were prepared. The 2-(methoxymethyl)ellipticinium salts 24 and 25, as well as the (methylthio)methyl congener 26, were relatively potent anticancer agents which displayed cytotoxicity selectivity profiles similar to compound 6. The cytotoxic dihydroellipticines 9 and 10 exhibited potencies approaching that of ellipticine itself in facilitating the formation of a ''cleavable complex'', while the least cytotoxic ellipticine derivatives exhibited no cleavage above background.