7-ethynyl-4-(trifluoromethyl)coumarin | 912850-47-6

• 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: 7-ethynyl-4-(trifluoromethyl)coumarin
• 英文别名: 7-Ethynyl-4-(trifluoromethyl)chromen-2-one；7-ethynyl-4-(trifluoromethyl)chromen-2-one
• CAS: 912850-47-6
• 化学式: C₁₂H₅F₃O₂
• 分子量: 238.166
• InChiKey: OPKRKOZSKAZRDM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N-乙酰-L-半胱氨酸 、 7-ethynyl-4-(trifluoromethyl)coumarin 在 四苯基卟啉 、 乙烷,三氯氟- 作用下， 以 二甲基亚砜 为溶剂， 以66%的产率得到
  参考文献：
  名称：

  光氧化还原硫醇-炔反应合成乙烯基硫基香豆素及其对荧光性质的影响

  摘要：

  开发了一种水相容性、基于光氧化还原的荧光香豆素合成方法，带有乙烯基硫醚作为给电子基团；随后，检查了这些衍生物的光物理性质。

  DOI：

  10.1002/chem.202401396
• 作为产物：
  描述：

  7-羟基-4-三氟甲基香豆素 、 三甲基乙炔基硅 在 吡啶 、 三氟甲磺酸酐 、 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 二异丙胺 、 四丁基氟化铵 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以45%的产率得到7-ethynyl-4-(trifluoromethyl)coumarin
  参考文献：
  名称：

  7-Ethynylcoumarins: Selective Inhibitors of Human Cytochrome P450s 1A1 and 1A2

  摘要：

  To discover new selective mechanism-based P450 inhibitors, eight 7-ethynylcoumarin derivatives were prepared through a facile two-step synthetic route. Cytochrome P450 activity assays indicated that introduction of functional groups in the backbone of coumarin could enhance the inhibition activities toward P450s 1A1 and 1A2, providing good selectivity against P450s 2A6 and 2B1. The most potent product 7-ethyny1-3,4,8-trimethylcoumarin (7ETMC) showed IC50 values of 0.46 mu M and 0.50 mu M for P450s 1A1 and 1A2 in the first six minutes, respectively, and did not show any inhibition activity for P450s 2A6 and 2B1 even at the dose of 50 mu M. All of the inhibitors except 7-ethyny1-3-methy1-4-phenylcoumarin (7E3M41PC) showed mechanism-based inhibition of P450s 1A1 and 1A2. In order to explain this mechanistic difference in inhibitory activities, X-ray crystallography data were used to study the difference in conformation between 7E3M4PC and the other compounds studied. Docking simulations indicated that the binding orientations and affinities resulted in different behaviors of the inhibitors on P450 1A2. Specifically, 7E3M4PC with its two-plane structure fits into the P450 1A2's active site cavity with an orientation leading to no reactive binding, causing it to act as a competitive inhibitor.

  DOI：

  10.1021/tx300023p

文献信息

• 7-Ethynylcoumarins: Selective Inhibitors of Human Cytochrome P450s 1A1 and 1A2
  作者：Jiawang Liu、Thong T. Nguyen、Patrick S. Dupart、Jayalakshmi Sridhar、Xiaoyi Zhang、Naijue Zhu、Cheryl L. Klein Stevens、Maryam Foroozesh

  DOI：10.1021/tx300023p

  日期：2012.5.21

  To discover new selective mechanism-based P450 inhibitors, eight 7-ethynylcoumarin derivatives were prepared through a facile two-step synthetic route. Cytochrome P450 activity assays indicated that introduction of functional groups in the backbone of coumarin could enhance the inhibition activities toward P450s 1A1 and 1A2, providing good selectivity against P450s 2A6 and 2B1. The most potent product 7-ethyny1-3,4,8-trimethylcoumarin (7ETMC) showed IC50 values of 0.46 mu M and 0.50 mu M for P450s 1A1 and 1A2 in the first six minutes, respectively, and did not show any inhibition activity for P450s 2A6 and 2B1 even at the dose of 50 mu M. All of the inhibitors except 7-ethyny1-3-methy1-4-phenylcoumarin (7E3M41PC) showed mechanism-based inhibition of P450s 1A1 and 1A2. In order to explain this mechanistic difference in inhibitory activities, X-ray crystallography data were used to study the difference in conformation between 7E3M4PC and the other compounds studied. Docking simulations indicated that the binding orientations and affinities resulted in different behaviors of the inhibitors on P450 1A2. Specifically, 7E3M4PC with its two-plane structure fits into the P450 1A2's active site cavity with an orientation leading to no reactive binding, causing it to act as a competitive inhibitor.