2-(3-methoxyphenyl)-4H-benzo[h]chromen-4-one | 71601-13-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 2-(3-methoxyphenyl)-4H-benzo[h]chromen-4-one
• 英文别名: 2-(3-Methoxyphenyl)benzo[h]chromen-4-one
• CAS: 71601-13-3
• 化学式: C₂₀H₁₄O₃
• 分子量: 302.329
• InChiKey: PGRWDFOTLBQRCE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(3-methoxyphenyl)-4H-benzo[h]chromen-4-one 在 氢溴酸 、 sodium hydride 、 溶剂黄146 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.25h， 生成 O-(3-(4-oxo-4H-benzo[h]chromen-2-yl)phenyl)dimethylcarbamothioate
  参考文献：
  名称：

  Design and synthesis of selective CYP1B1 inhibitor via dearomatization of α-naphthoflavone

  摘要：

  Selective cytochrome P450 (CYP) 1B1 inhibition has potential as an anticancer strategy that is unrepresented in the current clinical arena. For development of a selective inhibitor, we focused on the complexity caused by sp(3)-hybridized carbons and synthesized a series of benzo[h] chromone derivatives linked to a non-aromatic B-ring using alpha-naphthoflavone (ANF) as the lead compound. Ring structure comparison suggested compound 37 as a suitable cyclohexyl-core with improved solubility. Structural evolution of 37 produced the azide-containing cis-49a, which had good properties in three important respects: (1) selectivity for CYP1B1 over CYP1A1 and CYP1A2 (120-times and 150-times, respectively), (2) greater inhibitory potency of > 2 times that of ANF, and (3) improved solubility. The corresponding aromatic B-ring compound 59a showed low selectivity and poor solubility. To elucidate the binding mode, we performed X-ray crystal structure analysis, which revealed the interaction mode and explained the subtype selectivity of cis-49a.

  DOI：

  10.1016/j.bmc.2018.11.045
• 作为产物：
  描述：

  2-乙酰基-1-萘酚 在 4-二甲氨基吡啶 、 硫酸 、 sodium hydride 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 2-(3-methoxyphenyl)-4H-benzo[h]chromen-4-one
  参考文献：
  名称：

  α-萘黄酮衍生物作为CYP1B1抑制剂的合成及构效关系研究。

  摘要：

  细胞色素P450 1B1（CYP1B1）被公认为是预防癌症和逆转耐药性的重要靶标。为了获得有效和选择性的CYP1B1抑制剂，合成了一系列41种α-萘黄酮（ANF）衍生物，进行了表征，并评估了其对CYP1B1，CYP1A1和CYP1A2的抑制活性。封闭结构对CYP1B1抑制作用的活性关系研究表明，修饰ANF的C环会降低CYP1B1的抑制能力，而在B环的不同位置引入取代基会产生类似的变化CYP1B1的抑制能力。在这些衍生物中，化合物9e和9j被确定为最有效的两种选择性CYP1B1抑制剂，IC50值分别为0.49和0.52 nM，其效力比先导化合物ANF强10倍。此外，进行了分子对接和合理的3D-QSAR（三维定量结构-活性关系）研究，以更好地理解影响CYP1B1抑制活性的关键结构特征。这项研究中获得的结果将为将来开发选择性，有效，低毒和水溶性CYP1B1抑制剂奠定基础。

  DOI：

  10.1016/j.ejmech.2019.111938

文献信息

• Synthesis of methoxybenzoflavones and assignments of their NMR data
  作者：Doseok Hwang、Geunhyeong Jo、Jiye Hyun、Sung Dae Lee、Dongsoo Koh、Yoongho Lim

  DOI：10.1002/mrc.3790

  日期：2012.1

  also is a potent phytotoxin. Six 7,8‐benzoflavones and eight 5,6‐benzoflavones were synthesized in this study. The NMR data for a few of these compounds have been previously reported; however, the NMR data for most of them have not been reported. For reference purposes, the complete NMR data for the 14 benzoflavones are described. Copyright © 2012 John Wiley & Sons, Ltd.

  来自 Acroptilon repens 的植物毒性根系分泌物被鉴定为 7,8-苯黄酮，一种细胞色素 P450 1A2 抑制剂和细胞色素 P450 3A4 激活剂。合成的 5,6-苯并黄酮也是一种有效的植物毒素。本研究合成了 6 种 7,8-苯并黄酮和 8 种 5,6-苯并黄酮。其中一些化合物的 NMR 数据以前已经报道过；然而，其中大部分的核磁共振数据尚未报道。出于参考目的，描述了 14 种苯黄酮的完整 NMR 数据。版权所有 © 2012 John Wiley & Sons, Ltd.
• Fungal metabolism of naphthoflavones
  作者：Jarosław Popłoński、Sandra Sordon、Tomasz Tronina、Agnieszka Bartmańska、Ewa Huszcza

  DOI：10.1016/j.molcatb.2015.04.007

  日期：2015.7

  Naphthoflavones (benzoflavones) are synthetic flavonoids commonly used in drug metabolism studies as selective activators or inhibitors of cytochrome P-450 enzymes. Nowadays they are also used as a component of food supplements for body builders. There is no data regarding naphthoflavone microbial metabolism. In the present studies sixty-three fungal strains have been screened for their ability to transform alpha-naphthoflavone (7,8-benzoflavone) or beta-naphthoflavone (5,6-benzoflavone). Five strains belonging to the genera Penicillium, Cladosporium, Aspergillus and Verticillium transformed alpha-naphthoflavone and beta-naphthoflavone to the corresponding 4'-hydroxy derivatives. These selected fungi have been used in a further study on biotransformation of naphthoflavones with a differently substituted B-ring. Only 4'-methoxy derivatives have been transformed to the related 4'-hydroxy products. Selected strains are good biocatalysts to obtain 4'-hydroxy naphthoflavones in the one step reaction. (C) 2015 Elsevier B.V. All rights reserved.
• Torricelli, Jahrbuch der Philosophischen Fakultaet 2 [Zweite] der Universitaet Bern, 1922, vol. 2, p. 102
  作者：Torricelli

  DOI：——

  日期：——
• Design and synthesis of selective CYP1B1 inhibitor via dearomatization of α-naphthoflavone
  作者：Makoto Kubo、Keiko Yamamoto、Toshimasa Itoh

  DOI：10.1016/j.bmc.2018.11.045

  日期：2019.1

  Selective cytochrome P450 (CYP) 1B1 inhibition has potential as an anticancer strategy that is unrepresented in the current clinical arena. For development of a selective inhibitor, we focused on the complexity caused by sp(3)-hybridized carbons and synthesized a series of benzo[h] chromone derivatives linked to a non-aromatic B-ring using alpha-naphthoflavone (ANF) as the lead compound. Ring structure comparison suggested compound 37 as a suitable cyclohexyl-core with improved solubility. Structural evolution of 37 produced the azide-containing cis-49a, which had good properties in three important respects: (1) selectivity for CYP1B1 over CYP1A1 and CYP1A2 (120-times and 150-times, respectively), (2) greater inhibitory potency of > 2 times that of ANF, and (3) improved solubility. The corresponding aromatic B-ring compound 59a showed low selectivity and poor solubility. To elucidate the binding mode, we performed X-ray crystal structure analysis, which revealed the interaction mode and explained the subtype selectivity of cis-49a.
• Synthesis and structure-activity relationship studies of α-naphthoflavone derivatives as CYP1B1 inhibitors
  作者：Jinyun Dong、Zengtao Wang、Jiahua Cui、Qingqing Meng、Shaoshun Li

  DOI：10.1016/j.ejmech.2019.111938

  日期：2020.2

  CYP1B1 inhibitory capacity. Among these derivatives, compounds 9e and 9j were identified as the most potent two selective CYP1B1 inhibitors with IC50 values of 0.49 and 0.52 nM, respectively, which were 10-fold more potent than the lead compound ANF. In addition, molecular docking and a reasonable 3D-QSAR (three-dimensional quantitative structure-activity relationship) study were performed to provide a

  细胞色素P450 1B1（CYP1B1）被公认为是预防癌症和逆转耐药性的重要靶标。为了获得有效和选择性的CYP1B1抑制剂，合成了一系列41种α-萘黄酮（ANF）衍生物，进行了表征，并评估了其对CYP1B1，CYP1A1和CYP1A2的抑制活性。封闭结构对CYP1B1抑制作用的活性关系研究表明，修饰ANF的C环会降低CYP1B1的抑制能力，而在B环的不同位置引入取代基会产生类似的变化CYP1B1的抑制能力。在这些衍生物中，化合物9e和9j被确定为最有效的两种选择性CYP1B1抑制剂，IC50值分别为0.49和0.52 nM，其效力比先导化合物ANF强10倍。此外，进行了分子对接和合理的3D-QSAR（三维定量结构-活性关系）研究，以更好地理解影响CYP1B1抑制活性的关键结构特征。这项研究中获得的结果将为将来开发选择性，有效，低毒和水溶性CYP1B1抑制剂奠定基础。