2-(2-fluoro-3,4-dimethoxyphenyl)-1-(5-methoxy-2,2-dimethyl-2H-chromen-6-yl)-2-methylpropan-1-ol

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 1,2-二芳基-2-丙烯-1-醇
• 英文名称: 2-(2-fluoro-3,4-dimethoxyphenyl)-1-(5-methoxy-2,2-dimethyl-2H-chromen-6-yl)-2-methylpropan-1-ol
• 英文别名: 2-(2-Fluoro-3,4-dimethoxyphenyl)-1-(5-methoxy-2,2-dimethylchromen-6-yl)-2-methylpropan-1-ol；2-(2-fluoro-3,4-dimethoxyphenyl)-1-(5-methoxy-2,2-dimethylchromen-6-yl)-2-methylpropan-1-ol
• 化学式: C₂₄H₂₉FO₅
• 分子量: 416.49
• InChiKey: LJOFWEKCNGUBDT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  57.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(2-fluoro-3,4-dimethoxyphenyl)-1-(5-methoxy-2,2-dimethyl-2H-chromen-6-yl)-2-methylpropan-1-ol 、 丙酰氯 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以70%的产率得到2-(2-fluoro-3,4-dimethoxyphenyl)-1-(5-methoxy-2,2-dimethyl-2H-chromen-6-yl)-2-methylpropyl propionate
  参考文献：
  名称：

  Ring-truncated deguelin derivatives as potent Hypoxia Inducible Factor-1α (HIF-1α) inhibitors

  摘要：

  A series of fluorophenyl and pyridine analogues of 1 and 2 were synthesized as ring-truncated deguelin surrogates and evaluated for their HIF-1 alpha inhibition. Their structure-activity relationship was systematically investigated based on the variation of the linker B-region moiety. Among the inhibitors, compound 25 exhibited potent HIF-1 alpha inhibition in a dose-dependent manner and significant antitumor activity in H1299 with less toxicity than deguelin. It also inhibited in vitro hypoxia-mediated angiogenic processes in HRMECs. The docking study indicates that 25 occupied the C-terminal ATP-binding pocket of HSP90 in a similar mode as 1, which implies that the anticancer and antiangiogenic activities of 25 are derived from HIF-1 alpha destabilization by binding to the C-terminal ATP-binding site of hHSP90. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.09.033
• 作为产物：
  描述：

  2-氟-3,4-二甲氧基苄氯 在 sodium tetrahydroborate 、 正丁基锂 、 偶氮二异丁腈 、 三正丁基氢锡 、 sodium hydride 、 戴斯-马丁氧化剂 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 5.33h， 生成 2-(2-fluoro-3,4-dimethoxyphenyl)-1-(5-methoxy-2,2-dimethyl-2H-chromen-6-yl)-2-methylpropan-1-ol
  参考文献：
  名称：

  Ring-truncated deguelin derivatives as potent Hypoxia Inducible Factor-1α (HIF-1α) inhibitors

  摘要：

  A series of fluorophenyl and pyridine analogues of 1 and 2 were synthesized as ring-truncated deguelin surrogates and evaluated for their HIF-1 alpha inhibition. Their structure-activity relationship was systematically investigated based on the variation of the linker B-region moiety. Among the inhibitors, compound 25 exhibited potent HIF-1 alpha inhibition in a dose-dependent manner and significant antitumor activity in H1299 with less toxicity than deguelin. It also inhibited in vitro hypoxia-mediated angiogenic processes in HRMECs. The docking study indicates that 25 occupied the C-terminal ATP-binding pocket of HSP90 in a similar mode as 1, which implies that the anticancer and antiangiogenic activities of 25 are derived from HIF-1 alpha destabilization by binding to the C-terminal ATP-binding site of hHSP90. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.09.033