7-(3,5-dibromophenyl)-7,11-dihydrobenzo[h]furo[3,4-b]quinolin-8(10H)-one | 1309571-45-6

• 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: 7-(3,5-dibromophenyl)-7,11-dihydrobenzo[h]furo[3,4-b]quinolin-8(10H)-one
• 英文别名: 11-(3,5-Dibromophenyl)-14-oxa-17-azatetracyclo[8.7.0.02,7.012,16]heptadeca-1(10),2,4,6,8,12(16)-hexaen-13-one
• CAS: 1309571-45-6
• 化学式: C₂₁H₁₃Br₂NO₂
• 分子量: 471.148
• InChiKey: JORUENNNXFVNOO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  26
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-(3,5-dibromophenyl)-7,11-dihydrobenzo[h]furo[3,4-b]quinolin-8(10H)-one 以 乙醇 、 二氯甲烷 为溶剂， 以Ca. 15 mg的产率得到(11R)-11-(3,5-dibromophenyl)-14-oxa-17-azatetracyclo[8.7.0.02,7.012,16]heptadeca-1(10),2,4,6,8,12(16)-hexaen-13-one
  参考文献：
  名称：

  Anticancer Properties of an Important Drug Lead Podophyllotoxin Can Be Efficiently Mimicked by Diverse Heterocyclic Scaffolds Accessible via One-Step Synthesis

  摘要：

  Structural simplification of an antimitotic natural product podophyllotoxin with mimetic heterocyclic scaffolds constructed using multicomponent reactions led to the identification of compounds exhibiting low nanomolar antiproliferative and apoptosis-inducing properties. The most potent compounds were found in the dihydropyridopyrazole, dihydropyridonaphthalene, dihydropyridoindole, and dihydropyridopyrimidine scaffold series. Biochemical mechanistic studies, performed with dihydropyridopyrazole compounds showed that these heterocycles inhibit in vitro tubulin polymerization and disrupt the formation of mitotic spindles in dividing cells at low nanomolar concentrations, in a manner similar to podophyllotoxin itself. Separation of a racemic dihydropyridonaphthalene into individual enantiomers demonstrated that only the optical antipode matching the absolute configuration of podophyllotoxin possessed potent anticancer activity. Computer modeling, performed using the podophyllotoxin binding site on P-tubulin, provided a theoretical understanding of these successful experimental findings.

  DOI：

  10.1021/jm200410r
• 作为产物：
  描述：

  4-羟乙酰乙酸内酯 、 3,5-二溴苯甲醛 、 1-萘胺 以 乙醇 为溶剂， 以39%的产率得到7-(3,5-dibromophenyl)-7,11-dihydrobenzo[h]furo[3,4-b]quinolin-8(10H)-one
  参考文献：
  名称：

  Anticancer Properties of an Important Drug Lead Podophyllotoxin Can Be Efficiently Mimicked by Diverse Heterocyclic Scaffolds Accessible via One-Step Synthesis

  摘要：

  Structural simplification of an antimitotic natural product podophyllotoxin with mimetic heterocyclic scaffolds constructed using multicomponent reactions led to the identification of compounds exhibiting low nanomolar antiproliferative and apoptosis-inducing properties. The most potent compounds were found in the dihydropyridopyrazole, dihydropyridonaphthalene, dihydropyridoindole, and dihydropyridopyrimidine scaffold series. Biochemical mechanistic studies, performed with dihydropyridopyrazole compounds showed that these heterocycles inhibit in vitro tubulin polymerization and disrupt the formation of mitotic spindles in dividing cells at low nanomolar concentrations, in a manner similar to podophyllotoxin itself. Separation of a racemic dihydropyridonaphthalene into individual enantiomers demonstrated that only the optical antipode matching the absolute configuration of podophyllotoxin possessed potent anticancer activity. Computer modeling, performed using the podophyllotoxin binding site on P-tubulin, provided a theoretical understanding of these successful experimental findings.

  DOI：

  10.1021/jm200410r

文献信息

• Anticancer Properties of an Important Drug Lead Podophyllotoxin Can Be Efficiently Mimicked by Diverse Heterocyclic Scaffolds Accessible via One-Step Synthesis
  作者：Igor V. Magedov、Liliya Frolova、Madhuri Manpadi、Uma devi Bhoga、Hong Tang、Nikolai M. Evdokimov、Olivia George、Kathy Hadje Georgiou、Steffen Renner、Matthäus Getlik、Tiffany L. Kinnibrugh、Manuel A. Fernandes、Severine Van slambrouck、Wim F. A. Steelant、Charles B. Shuster、Snezna Rogelj、Willem A. L. van Otterlo、Alexander Kornienko

  DOI：10.1021/jm200410r

  日期：2011.6.23

  Structural simplification of an antimitotic natural product podophyllotoxin with mimetic heterocyclic scaffolds constructed using multicomponent reactions led to the identification of compounds exhibiting low nanomolar antiproliferative and apoptosis-inducing properties. The most potent compounds were found in the dihydropyridopyrazole, dihydropyridonaphthalene, dihydropyridoindole, and dihydropyridopyrimidine scaffold series. Biochemical mechanistic studies, performed with dihydropyridopyrazole compounds showed that these heterocycles inhibit in vitro tubulin polymerization and disrupt the formation of mitotic spindles in dividing cells at low nanomolar concentrations, in a manner similar to podophyllotoxin itself. Separation of a racemic dihydropyridonaphthalene into individual enantiomers demonstrated that only the optical antipode matching the absolute configuration of podophyllotoxin possessed potent anticancer activity. Computer modeling, performed using the podophyllotoxin binding site on P-tubulin, provided a theoretical understanding of these successful experimental findings.