ethyl 3-(9-oxo-7-phenyl-6H-pyrrolo[3,2-f]quinolin-3(9H)-yl)propanoate | 1246292-59-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: ethyl 3-(9-oxo-7-phenyl-6H-pyrrolo[3,2-f]quinolin-3(9H)-yl)propanoate
• 英文别名: ethyl 3-(9-oxo-7-phenyl-6H-pyrrolo[3,2-f]quinolin-3-yl)propanoate
• CAS: 1246292-59-0
• 化学式: C₂₂H₂₀N₂O₃
• 分子量: 360.412
• InChiKey: XPQJLRNKOTVYFP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  60.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 3-(9-oxo-7-phenyl-6H-pyrrolo[3,2-f]quinolin-3(9H)-yl)propanoate 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 以70%的产率得到3-(3-hydroxypropyl)-7-phenyl-3H-pyrrolo[3,2-f]quinolin-9(6H)-one
  参考文献：
  名称：

  Novel 3-Substituted 7-Phenylpyrrolo[3,2-f]quinolin-9(6H)-ones as Single Entities with Multitarget Antiproliferative Activity

  摘要：

  A series of chemically modified 7-phenylpyrrolo[3,2-f]quinolinones was synthesized and evaluated as anticancer agents. Among them, the most cytotoxic (subnanomolar GI(50) values) amidic derivative 5f was shown to act as an inhibitor of tubulin polymerization (IC50, 0.99 mu M) by binding to the colchicine site with high affinity. Moreover, 5f induced cell cycle arrest in the G2/M phase of the cell cycle in a concentration dependent manner, followed by caspase-dependent apoptotic cell death. Compound 5f also showed lower toxicity in nontumoral cells, suggesting selectivity toward cancer cells. Additional experiments revealed that 5f inhibited the enzymatic activity of multiple kinases, including AURKA, FLT3, GSK3A, MAP3K, MEK, RSK2, RSK4, PLK4, ULK1, and JAK1. Computational studies showed that 5f can be properly accommodated in the colchicine binding site of tubulin as well as in the ATP binding clefts of all examined kinases. Our data indicate that the excellent antiproliferative profile of 5f may be derived from its interactions with multiple cellular targets.

  DOI：

  10.1021/acs.jmedchem.5b00805
• 作为产物：
  描述：

  ethyl 3-[1-(3-ethoxy-3-oxopropyl)-1H-indol-5-ylamino]-3-phenylacrylate 以 二苯醚 为溶剂， 反应 0.5h， 以45%的产率得到ethyl 3-(9-oxo-7-phenyl-6H-pyrrolo[3,2-f]quinolin-3(9H)-yl)propanoate
  参考文献：
  名称：

  显示有效和选择性抗白血病活性的 3H-吡咯并[3,2-f]喹啉-9-one 衍生物的合成和体外评价

  摘要：

  一系列新的取代的7-苯基-3- ħ吡咯并[3,2- ˚F ]喹啉-9-酮的合成和评价它们的抗增殖活性。最活跃的衍生物对人类白血病细胞系显示出高选择性并有效抑制它们的生长，GI 50值在纳摩尔范围内。活性化合物强烈阻断微管蛋白组装和秋水仙碱与微管蛋白的结合。它们的活性等于或大于参考化合物考布他汀 A-4 的活性。流式细胞术研究表明，两种最活跃的化合物在 G 2/M 细胞周期阶段以浓度依赖性方式。这种效应与细胞凋亡、线粒体去极化、活性氧的产生、caspase-3 的激活和聚（ADP-核糖）聚合酶的裂解有关。

  DOI：

  10.1002/cmdc.201000180

文献信息

• Synthesis and in vitro Evaluation of 3H-Pyrrolo[3,2-f]quinolin-9-one Derivatives That Show Potent and Selective Anti-leukemic Activity
  作者：Maria Grazia Ferlin、Roberta Bortolozzi、Paola Brun、Ignazio Castagliuolo、Ernest Hamel、Giuseppe Basso、Giampietro Viola

  DOI：10.1002/cmdc.201000180

  日期：——

  2‐f]quinolin‐9‐ones were synthesized and evaluated for their antiproliferative activity. The most active derivatives showed high selectivity against human leukemia cell lines and potently inhibited their growth, with GI50 values in the nanomolar range. The active compounds strongly blocked tubulin assembly and colchicine binding to tubulin. Their activities were equal to or greater than that of the

  一系列新的取代的7-苯基-3- ħ吡咯并[3,2- ˚F ]喹啉-9-酮的合成和评价它们的抗增殖活性。最活跃的衍生物对人类白血病细胞系显示出高选择性并有效抑制它们的生长，GI 50值在纳摩尔范围内。活性化合物强烈阻断微管蛋白组装和秋水仙碱与微管蛋白的结合。它们的活性等于或大于参考化合物考布他汀 A-4 的活性。流式细胞术研究表明，两种最活跃的化合物在 G 2/M 细胞周期阶段以浓度依赖性方式。这种效应与细胞凋亡、线粒体去极化、活性氧的产生、caspase-3 的激活和聚（ADP-核糖）聚合酶的裂解有关。
• Novel 3-Substituted 7-Phenylpyrrolo[3,2-<i>f</i>]quinolin-9(6<i>H</i>)-ones as Single Entities with Multitarget Antiproliferative Activity
  作者：Davide Carta、Roberta Bortolozzi、Ernest Hamel、Giuseppe Basso、Stefano Moro、Giampietro Viola、Maria Grazia Ferlin

  DOI：10.1021/acs.jmedchem.5b00805

  日期：2015.10.22

  A series of chemically modified 7-phenylpyrrolo[3,2-f]quinolinones was synthesized and evaluated as anticancer agents. Among them, the most cytotoxic (subnanomolar GI(50) values) amidic derivative 5f was shown to act as an inhibitor of tubulin polymerization (IC50, 0.99 mu M) by binding to the colchicine site with high affinity. Moreover, 5f induced cell cycle arrest in the G2/M phase of the cell cycle in a concentration dependent manner, followed by caspase-dependent apoptotic cell death. Compound 5f also showed lower toxicity in nontumoral cells, suggesting selectivity toward cancer cells. Additional experiments revealed that 5f inhibited the enzymatic activity of multiple kinases, including AURKA, FLT3, GSK3A, MAP3K, MEK, RSK2, RSK4, PLK4, ULK1, and JAK1. Computational studies showed that 5f can be properly accommodated in the colchicine binding site of tubulin as well as in the ATP binding clefts of all examined kinases. Our data indicate that the excellent antiproliferative profile of 5f may be derived from its interactions with multiple cellular targets.