6',7'-Dihydroxy-8-geranylpsoralen

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 6',7'-Dihydroxy-8-geranylpsoralen
• 英文别名: 9-[(6',7'-dihydroxy-3',7'-dimethyl-2'-octenyl)oxy]-7H-furo[3,2-g][1]benzopyran-7-one；8-(6,7-dihydroxy-3,7-dimethyl-2E-octenyloxy)psoralen；8-[(6,7-Dihydroxy-3,7-dimethyloct-2-en-1-yl)oxy]psoralen；9-[(E)-6,7-dihydroxy-3,7-dimethyloct-2-enoxy]furo[3,2-g]chromen-7-one
• 化学式: C₂₁H₂₄O₆
• 分子量: 372.418
• InChiKey: HWQSPRJGHSGSPF-MDWZMJQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  89.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  花椒毒醇 在 disodium hydrogenphosphate 、 硫酸 、 双氧水 、 potassium carbonate 、 六氟丙酮 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 36.25h， 生成 6',7'-Dihydroxy-8-geranylpsoralen
  参考文献：
  名称：

  Synthesis of 8-geranyloxypsoralen analogues and their evaluation as inhibitors of CYP3A4

  摘要：

  Furanocoutnarins have been shown to inhibit CYP3A4 in vitro with varying degrees of potency [Pharmacogeneties 1997, 7, 391-396; Chem. Res. Toxicol. 1998, 11, 252-259; Drug Metab. Dispos. 1997, 25, 1228-1233; Br. J. Pharmacol 2000, 130, 13691377]. In this study, we report the effects of a series of novel furanocoumarins based on the naturally Occurring derivative 8-geranylepoxypsoralen which has been shown to be a more potent inhibitor of CYP3A4 than its 5-position-substituted counterpart bergamottin [Drug Metab. Dispos. 2000, 28, 766-771; Jpn. J. Pharmacol. 2000, 82, 122-129]. Compounds were designed, synthesised and tested for their ability to inhibit CYP3A4 activity in human liver microsomes using testosterone as the marker Substrate. Both the saturated and unsaturated phenolic furanocoumarin derivatives were found to be inactive. However, the 8-alkyloxy-furanocoumarin analogues were shown to inhibit CYP3A4 activity in a dose dependent manner, with IC50 values ranging from 0.78 +/- 0.11 to 3.93 +/- 0.53 mu M. The reduced furan derivative dihydro-8-geranyloxypsoralen showed a 4-fold decrease in inhibitory potency, suggesting that the furan moiety plays a role in the interaction between these compounds and CYP3A4. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.01.046

文献信息

• Synthesis of 8-geranyloxypsoralen analogues and their evaluation as inhibitors of CYP3A4
  作者：E.C. Row、S.A. Brown、A.V. Stachulski、M.S. Lennard

  DOI：10.1016/j.bmc.2006.01.046

  日期：2006.6

  Furanocoutnarins have been shown to inhibit CYP3A4 in vitro with varying degrees of potency [Pharmacogeneties 1997, 7, 391-396; Chem. Res. Toxicol. 1998, 11, 252-259; Drug Metab. Dispos. 1997, 25, 1228-1233; Br. J. Pharmacol 2000, 130, 13691377]. In this study, we report the effects of a series of novel furanocoumarins based on the naturally Occurring derivative 8-geranylepoxypsoralen which has been shown to be a more potent inhibitor of CYP3A4 than its 5-position-substituted counterpart bergamottin [Drug Metab. Dispos. 2000, 28, 766-771; Jpn. J. Pharmacol. 2000, 82, 122-129]. Compounds were designed, synthesised and tested for their ability to inhibit CYP3A4 activity in human liver microsomes using testosterone as the marker Substrate. Both the saturated and unsaturated phenolic furanocoumarin derivatives were found to be inactive. However, the 8-alkyloxy-furanocoumarin analogues were shown to inhibit CYP3A4 activity in a dose dependent manner, with IC50 values ranging from 0.78 +/- 0.11 to 3.93 +/- 0.53 mu M. The reduced furan derivative dihydro-8-geranyloxypsoralen showed a 4-fold decrease in inhibitory potency, suggesting that the furan moiety plays a role in the interaction between these compounds and CYP3A4. (c) 2006 Elsevier Ltd. All rights reserved.