2,3-dihydro-2-(2-isopropenyl)-6-hydroxy-7-nitrobenzofuran | 586963-74-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 香豆素
• 英文名称: 2,3-dihydro-2-(2-isopropenyl)-6-hydroxy-7-nitrobenzofuran
• 英文别名: 6-Benzofuranol, 2,3-dihydro-2-(1-methylethenyl)-7-nitro-；7-nitro-2-prop-1-en-2-yl-2,3-dihydro-1-benzofuran-6-ol
• CAS: 586963-74-8
• 化学式: C₁₁H₁₁NO₄
• 分子量: 221.213
• InChiKey: VUBATMAICMDCMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  75.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,3-dihydro-2-(2-isopropenyl)-6-hydroxy-7-nitrobenzofuran 在 palladium on activated charcoal 四氧化锇 、 氢气 、 N-甲基吗啉氧化物 作用下， 以 甲醇 、 丙酮 为溶剂， 20.0 ℃ 、8.67 kPa 条件下， 反应 2.0h， 生成 7-amino-2,3-dihydro-2(RS)-(1,2(RS)-dihydroxypropan-2-yl)-6-hydroxybenzofuran
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Psorospermin/Quinobenzoxazine Hybrids as Structurally Novel Antitumor Agents

  摘要：

  Topoisomerase II, an enzyme that catalyzes changes in the topology of DNA, plays several key roles in DNA metabolism and chromosome structure, and it is the primary cytotoxic target for a number of clinically important DNA intercalating agents such as doxorubicin. It seems likely that if these intercalating topoisomerase II poisons are structurally modified to also be DNA alkylating agents, they will have increased dwell time on the topoisomerase II-DNA complex and increased potency and selectivity for cancer cells. On the basis of insights into the mechanisms of action of psorospermin and the quinobenzoxazine A-62176 and molecular modeling studies of these compounds with duplex DNA, we have designed and synthesized a series of novel hybrid DNA-interactive compounds that alkylate DNA most efficiently at sequences directed by topoisomerase II. The epoxydihydrofuran ring of psorospermin was used as a DNA alkylating moiety, and this was fused to the pyridobenzophenoxazine ring of A-62176. The chlorohydrin ring opened form of the epoxide was also prepared and tested. These hybrid compounds showed enhanced DNA alkylating activity in the presence of topoisomerase II, exhibited significant activity against all the cancer cells tested at submicromolar concentrations, and were more potent than both parent compounds. However, the biochemical assays indicated that they lost some of the topoisomerase II and Mg2+ dependency for reaction with DNA that is associated with psorospermin and A-62176, respectively.

  DOI：

  10.1021/jm030096i
• 作为产物：
  描述：

  1,4-二溴-2-甲基-2-丁烯 、 2-硝基间苯二酚 在 正丁基锂 作用下， 以 正己烷 、 甲苯 为溶剂， 反应 22.25h， 以23%的产率得到2,3-dihydro-2-(2-isopropenyl)-6-hydroxy-7-nitrobenzofuran
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Psorospermin/Quinobenzoxazine Hybrids as Structurally Novel Antitumor Agents

  摘要：

  Topoisomerase II, an enzyme that catalyzes changes in the topology of DNA, plays several key roles in DNA metabolism and chromosome structure, and it is the primary cytotoxic target for a number of clinically important DNA intercalating agents such as doxorubicin. It seems likely that if these intercalating topoisomerase II poisons are structurally modified to also be DNA alkylating agents, they will have increased dwell time on the topoisomerase II-DNA complex and increased potency and selectivity for cancer cells. On the basis of insights into the mechanisms of action of psorospermin and the quinobenzoxazine A-62176 and molecular modeling studies of these compounds with duplex DNA, we have designed and synthesized a series of novel hybrid DNA-interactive compounds that alkylate DNA most efficiently at sequences directed by topoisomerase II. The epoxydihydrofuran ring of psorospermin was used as a DNA alkylating moiety, and this was fused to the pyridobenzophenoxazine ring of A-62176. The chlorohydrin ring opened form of the epoxide was also prepared and tested. These hybrid compounds showed enhanced DNA alkylating activity in the presence of topoisomerase II, exhibited significant activity against all the cancer cells tested at submicromolar concentrations, and were more potent than both parent compounds. However, the biochemical assays indicated that they lost some of the topoisomerase II and Mg2+ dependency for reaction with DNA that is associated with psorospermin and A-62176, respectively.

  DOI：

  10.1021/jm030096i

文献信息

• Design, Synthesis, and Evaluation of Psorospermin/Quinobenzoxazine Hybrids as Structurally Novel Antitumor Agents
  作者：Mu-Yong Kim、Younghwa Na、Hariprasad Vankayalapati、Mary Gleason-Guzman、Laurence H. Hurley

  DOI：10.1021/jm030096i

  日期：2003.7.1

  Topoisomerase II, an enzyme that catalyzes changes in the topology of DNA, plays several key roles in DNA metabolism and chromosome structure, and it is the primary cytotoxic target for a number of clinically important DNA intercalating agents such as doxorubicin. It seems likely that if these intercalating topoisomerase II poisons are structurally modified to also be DNA alkylating agents, they will have increased dwell time on the topoisomerase II-DNA complex and increased potency and selectivity for cancer cells. On the basis of insights into the mechanisms of action of psorospermin and the quinobenzoxazine A-62176 and molecular modeling studies of these compounds with duplex DNA, we have designed and synthesized a series of novel hybrid DNA-interactive compounds that alkylate DNA most efficiently at sequences directed by topoisomerase II. The epoxydihydrofuran ring of psorospermin was used as a DNA alkylating moiety, and this was fused to the pyridobenzophenoxazine ring of A-62176. The chlorohydrin ring opened form of the epoxide was also prepared and tested. These hybrid compounds showed enhanced DNA alkylating activity in the presence of topoisomerase II, exhibited significant activity against all the cancer cells tested at submicromolar concentrations, and were more potent than both parent compounds. However, the biochemical assays indicated that they lost some of the topoisomerase II and Mg2+ dependency for reaction with DNA that is associated with psorospermin and A-62176, respectively.