4-[(1,3-Dihydro-2h-pyrrolo[3,4-b]quinolin-2-yl)carbonyl]dihydro-3-methylene-2(3h)-furanone | 410537-96-1

• 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: 4-[(1,3-Dihydro-2h-pyrrolo[3,4-b]quinolin-2-yl)carbonyl]dihydro-3-methylene-2(3h)-furanone
• 英文别名: 4-(1,3-dihydropyrrolo[3,4-b]quinoline-2-carbonyl)-3-methylideneoxolan-2-one
• CAS: 410537-96-1
• 化学式: C₁₇H₁₄N₂O₃
• 分子量: 294.31
• InChiKey: ZBNZDAFYCKBXCS-UHFFFAOYSA-N

物化性质

• 沸点：
  605.2±55.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.81
• 重原子数：
  22.0
• 可旋转键数：
  1.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  59.5
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  4-[(1,3-Dihydro-2h-pyrrolo[3,4-b]quinolin-2-yl)carbonyl]dihydro-3-methylene-2(3h)-furanone 在 过氧化脲素 、 碳酸氢钠 、 三氟乙酸酐 作用下， 以 氯仿 为溶剂， 反应 24.0h， 以14%的产率得到
  参考文献：
  名称：

  Novel pyrrolo-quinoline derivatives as potent inhibitors for PI3-kinase related kinases

  摘要：

  Several pyrrolo-quinoline gamma -lactones were found as novel inhibitors for two members of the PI3-kinase related kinase (PIKK) family, Ataxia-Telangiectasia-mutated (ATM) protein and the mammalian Target of Rapamycin (mTOR). Preliminary structure-activity relationship studies indicated that an electrophilic exocyclic double bond conjugated to the carbonyl group of the gamma -lactone ring was crucial for the PIKK inhibitory potency. One of the best ATM inhibitors in this series, DK8G557, showed IC50 values of 0.6 and 7.0 muM for ATM and mTOR, respectively. This compound exhibited potent and selective growth inhibition activities in the NCI 60 human tumor cell line screen with a GI(50) MG-MID value of 2.69 muM. The best mTOR inhibitor in this series, HP9912, exhibited IC50 values of 0.5 and 6.5 muM for mTOR and ATM, respectively. These compounds suggest novel leads for the discovery of potent small molecule inhibitors of PIKKs as potential anticancer drugs, with therapeutic activities as either single, or as sensitizing agents to conventional radio-, or chemo-therapeutic strategies. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00260-7
• 作为产物：
  描述：

  1,1,2,2-乙烷四甲酸四乙酯 在 盐酸 、 草酰氯 、 甲基丙烯酸 、 sodium 、 三乙胺 作用下， 以 乙醇 、 氯仿 为溶剂， 反应 8.25h， 生成 4-[(1,3-Dihydro-2h-pyrrolo[3,4-b]quinolin-2-yl)carbonyl]dihydro-3-methylene-2(3h)-furanone
  参考文献：
  名称：

  Novel pyrrolo-quinoline derivatives as potent inhibitors for PI3-kinase related kinases

  摘要：

  Several pyrrolo-quinoline gamma -lactones were found as novel inhibitors for two members of the PI3-kinase related kinase (PIKK) family, Ataxia-Telangiectasia-mutated (ATM) protein and the mammalian Target of Rapamycin (mTOR). Preliminary structure-activity relationship studies indicated that an electrophilic exocyclic double bond conjugated to the carbonyl group of the gamma -lactone ring was crucial for the PIKK inhibitory potency. One of the best ATM inhibitors in this series, DK8G557, showed IC50 values of 0.6 and 7.0 muM for ATM and mTOR, respectively. This compound exhibited potent and selective growth inhibition activities in the NCI 60 human tumor cell line screen with a GI(50) MG-MID value of 2.69 muM. The best mTOR inhibitor in this series, HP9912, exhibited IC50 values of 0.5 and 6.5 muM for mTOR and ATM, respectively. These compounds suggest novel leads for the discovery of potent small molecule inhibitors of PIKKs as potential anticancer drugs, with therapeutic activities as either single, or as sensitizing agents to conventional radio-, or chemo-therapeutic strategies. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00260-7

文献信息

• Novel pyrrolo-quinoline derivatives as potent inhibitors for PI3-kinase related kinases
  作者：Hairuo Peng、Doeg-Il Kim、Jann N Sarkaria、Yong-Seo Cho、Robert T Abraham、Leon H Zalkow

  DOI：10.1016/s0968-0896(01)00260-7

  日期：2002.1

  Several pyrrolo-quinoline gamma -lactones were found as novel inhibitors for two members of the PI3-kinase related kinase (PIKK) family, Ataxia-Telangiectasia-mutated (ATM) protein and the mammalian Target of Rapamycin (mTOR). Preliminary structure-activity relationship studies indicated that an electrophilic exocyclic double bond conjugated to the carbonyl group of the gamma -lactone ring was crucial for the PIKK inhibitory potency. One of the best ATM inhibitors in this series, DK8G557, showed IC50 values of 0.6 and 7.0 muM for ATM and mTOR, respectively. This compound exhibited potent and selective growth inhibition activities in the NCI 60 human tumor cell line screen with a GI(50) MG-MID value of 2.69 muM. The best mTOR inhibitor in this series, HP9912, exhibited IC50 values of 0.5 and 6.5 muM for mTOR and ATM, respectively. These compounds suggest novel leads for the discovery of potent small molecule inhibitors of PIKKs as potential anticancer drugs, with therapeutic activities as either single, or as sensitizing agents to conventional radio-, or chemo-therapeutic strategies. (C) 2001 Elsevier Science Ltd. All rights reserved.