(6aS,8R)-4-cyclopropyl-11-fluoro-8-hydroxy-1,6-dioxo-1,4,5,6,6a,7,8,9-octahydropyrido[2,3-f]pyrrolo[1,2-a]quinoxaline-2-carboxylic acid | 957780-93-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: (6aS,8R)-4-cyclopropyl-11-fluoro-8-hydroxy-1,6-dioxo-1,4,5,6,6a,7,8,9-octahydropyrido[2,3-f]pyrrolo[1,2-a]quinoxaline-2-carboxylic acid
• 英文别名: (13R,15S)-3-cyclopropyl-9-fluoro-13-hydroxy-6,16-dioxo-3,11,17-triazatetracyclo[8.7.0.02,7.011,15]heptadeca-1,4,7,9-tetraene-5-carboxylic acid
• CAS: 957780-93-7
• 化学式: C₁₈H₁₆FN₃O₅
• 分子量: 373.341
• InChiKey: IDFREVDPBJMFAR-PELKAZGASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  110
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (2''S,4''R)-7-(2''-carboxypyrrolidin-1-yl)-1-cyclopropyl-6-fluoro-4''-hydroxy-8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 在 sodium dithionite 、 potassium carbonate 作用下， 以46%的产率得到(6aS,8R)-4-cyclopropyl-11-fluoro-8-hydroxy-1,6-dioxo-1,4,5,6,6a,7,8,9-octahydropyrido[2,3-f]pyrrolo[1,2-a]quinoxaline-2-carboxylic acid
  参考文献：
  名称：

  Heterocycles [h]-Fused onto 4-oxoquinoline-3-carboxylic acid, III.1 Facile synthesis and antitumor activity of model heterocycles [a]-fused onto pyrido[2,3-f]quinoxaline-3-carboxylic acids

  摘要：

  Direct interaction between 7-chloro-1-cyclopropyl-6-fluoro-8-nitro-4oxo-1,4-dihydroquinoline-3-carboxylic acid and each of (S)-proline, (2S,4R)-4hydroxyproline and (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid in hot aqueous ethanolic NaHCO3 yielded the corresponding optically pure N-(4-oxoquinolin-7-yl)-alpha-amino acids. The latter derivatives underwent reductive lactamization upon treatment with Na2S2O4 in aqueous ethanol to afford moderate yields of the respective pyrido[2,3-f]quinoxaline-3-carboxylic acid [fused]- to tetrahydropyrrolo[1,2-a]-, tetrahydrohydroxylpyrrolo [1,2-a] -and tetrahydroisoquinolino[2,3-a]heterocyclics 10-12, respectively. The antitumor activity against four human tumor cell lines showed that 10-12 displayed high levels of cytotoxicity as compared with Cisplatin. Interestingly, these compounds were more potent against breast carcinoma cell lines (MCF-7 and T-47D) than the lymphoid origin tumor cell lines (Jurkat and BHL-89). In particular, the (S)-proline derivative 10 exhibited preferential cytotoxicity to adherent cells (IC50 = 0.5 mu M), indicative of better potential in blocking the growth of solid tumors rather than the disseminated ones.

  DOI：

  10.1016/s0385-5414(07)81092-6

文献信息

• Heterocycles [h]-Fused onto 4-oxoquinoline-3-carboxylic acid, III.1 Facile synthesis and antitumor activity of model heterocycles [a]-fused onto pyrido[2,3-f]quinoxaline-3-carboxylic acids
  作者：M ABUSHUHEIL、M HASSUNEH、Y ALHIARI、A QAISI、M ELABADELAH

  DOI：10.1016/s0385-5414(07)81092-6

  日期：2007.10.1

  Direct interaction between 7-chloro-1-cyclopropyl-6-fluoro-8-nitro-4oxo-1,4-dihydroquinoline-3-carboxylic acid and each of (S)-proline, (2S,4R)-4hydroxyproline and (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid in hot aqueous ethanolic NaHCO3 yielded the corresponding optically pure N-(4-oxoquinolin-7-yl)-alpha-amino acids. The latter derivatives underwent reductive lactamization upon treatment with Na2S2O4 in aqueous ethanol to afford moderate yields of the respective pyrido[2,3-f]quinoxaline-3-carboxylic acid [fused]- to tetrahydropyrrolo[1,2-a]-, tetrahydrohydroxylpyrrolo [1,2-a] -and tetrahydroisoquinolino[2,3-a]heterocyclics 10-12, respectively. The antitumor activity against four human tumor cell lines showed that 10-12 displayed high levels of cytotoxicity as compared with Cisplatin. Interestingly, these compounds were more potent against breast carcinoma cell lines (MCF-7 and T-47D) than the lymphoid origin tumor cell lines (Jurkat and BHL-89). In particular, the (S)-proline derivative 10 exhibited preferential cytotoxicity to adherent cells (IC50 = 0.5 mu M), indicative of better potential in blocking the growth of solid tumors rather than the disseminated ones.