(2S,3R,4S,5R,6R)-2-(2-(((2-(2-(dimethylamino)ethyl)-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-5-yl)amino)methyl)phenoxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate | 937261-90-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2S,3R,4S,5R,6R)-2-(2-(((2-(2-(dimethylamino)ethyl)-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-5-yl)amino)methyl)phenoxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate
• CAS: 937261-90-0
• 化学式: C₃₅H₃₉N₃O₁₁
• 分子量: 677.708
• InChiKey: XVAANHUOSNBMHF-QOLYLGGMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  49.0
• 可旋转键数：
  12.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  170.24
• 氢给体数：
  2.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  (2S,3R,4S,5R,6R)-2-(2-(((2-(2-(dimethylamino)ethyl)-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-5-yl)amino)methyl)phenoxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate 在 potassium carbonate 作用下， 以 甲醇 、 水 为溶剂， 反应 0.25h， 以96%的产率得到5-{[(2-(2-phenoxy)-6-hydroxymethyltetrahydropyran-3,4,5-triol)-5-ylmethyl]amino}-N-(2-[2-(dimethylamino)ethyl]-1H-benzo[de]isoquinolin-1,3(2H)-dione)
  参考文献：
  名称：

  2,2,2-Trichloro-N-({2-[2-(dimethylamino)ethyl]-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin- 5-yl}carbamoyl)acetamide (UNBS3157), a Novel Nonhematotoxic Naphthalimide Derivative with Potent Antitumor Activity

  摘要：

  Amonafide (1), a naphthalimide which binds to DNA by intercalation and poisons topoisomerase II alpha, has demonstrated activity in phase II breast cancer trials, but has failed thus far to enter clinical phase III because of dose-limiting bone marrow toxicity. Compound 17 (one of 41 new compounds synthesized) is a novel anticancer naphthalimide with a distinct mechanism of action, notably inducing autophagy and senescence in cancer cells. Compound 17 (2,2,2-trichloro-N-({2-[2-(dimethylamino)ethyl]-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-5-yl}carbamoyl)acetamide (UNBS3157)) was found to have a 3-4-fold higher maximum tolerated dose compared to amonafide and not to provoke hematotoxicity in mice at doses that display significant antitumor effects. Furthermore, 17 has shown itself to be superior to amonafide in vivo in models of (i) L1210 murine leukemia, (ii) MXT-HI murine mammary adenocarcinoma, and (iii) orthotopic models of human A549 NSCLC and BxPC3 pancreatic cancer. Compound 17, therefore, merits further investigation as a potential anticancer agent.

  DOI：

  10.1021/jm070315q
• 作为产物：
  描述：

  氨萘非特 在 sodium cyanoborohydride 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 18.0h， 生成 (2S,3R,4S,5R,6R)-2-(2-(((2-(2-(dimethylamino)ethyl)-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-5-yl)amino)methyl)phenoxy)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate
  参考文献：
  名称：

  2,2,2-Trichloro-N-({2-[2-(dimethylamino)ethyl]-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin- 5-yl}carbamoyl)acetamide (UNBS3157), a Novel Nonhematotoxic Naphthalimide Derivative with Potent Antitumor Activity

  摘要：

  Amonafide (1), a naphthalimide which binds to DNA by intercalation and poisons topoisomerase II alpha, has demonstrated activity in phase II breast cancer trials, but has failed thus far to enter clinical phase III because of dose-limiting bone marrow toxicity. Compound 17 (one of 41 new compounds synthesized) is a novel anticancer naphthalimide with a distinct mechanism of action, notably inducing autophagy and senescence in cancer cells. Compound 17 (2,2,2-trichloro-N-({2-[2-(dimethylamino)ethyl]-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-5-yl}carbamoyl)acetamide (UNBS3157)) was found to have a 3-4-fold higher maximum tolerated dose compared to amonafide and not to provoke hematotoxicity in mice at doses that display significant antitumor effects. Furthermore, 17 has shown itself to be superior to amonafide in vivo in models of (i) L1210 murine leukemia, (ii) MXT-HI murine mammary adenocarcinoma, and (iii) orthotopic models of human A549 NSCLC and BxPC3 pancreatic cancer. Compound 17, therefore, merits further investigation as a potential anticancer agent.

  DOI：

  10.1021/jm070315q