3-(4-hydroxyphenyl)-8,8-dimethyl-4H,8H-pyrano[2,3-f]chromen-4-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异黄酮类化合物
• 英文名称: 3-(4-hydroxyphenyl)-8,8-dimethyl-4H,8H-pyrano[2,3-f]chromen-4-one
• 英文别名: 3-(4-hydroxyphenyl)-8, 8-dimethyl-8H-pyrano[2,3-f]-chromen-4-one；3-(4-hydroxyphenyl)-8,8-dimethyl-8H-pyrano[2,3-f]-chromen-4-one；3-(4-hydroxyphenyl)-8,8-dimethyl-8H-pyrano[2,3-f]chromen-4-one；3-(4-hydroxyphenyl)-8,8-dimethylpyrano[2,3-f]chromen-4(8H)-one；bidwillon C；derrone；3-(4-Hydroxyphenyl)-8,8-dimethylpyrano[2,3-f]chromen-4-one
• 化学式: C₂₀H₁₆O₄
• 分子量: 320.345
• InChiKey: GDSRNXASWYVDMP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(4-hydroxyphenyl)-8,8-dimethyl-4H,8H-pyrano[2,3-f]chromen-4-one 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙酸乙酯 为溶剂， 以73%的产率得到3-(4-hydroxyphenyl)-8,8-dimethyl-2,3,9,10-tetrahydropyrano[2,3-f]chromen-4(8H)-one
  参考文献：
  名称：

  Design, Synthesis, and Osteogenic Activity of Daidzein Analogs on Human Mesenchymal Stem Cells

  摘要：

  Osteoporosis is caused by an overstimulation of osteoclast activity and the destruction of the bone extracellular matrix. Without the normal architecture, osteoblast cells are unable to rebuild phenotypically normal bone. Hormone replacement therapy with estrogen has been effective in increasing osteoblast activity but also has resulted in the increased incidence of breast and uterine cancer. In this study we designed and synthesized a series of daidzein analogs to investigate their osteogenic induction potentials. Human bone marrow derived mesenchymal stem cells (MSCs) from three different donors were treated with daidzein analogs and demonstrated enhanced osteogenesis when compared to daidzein treatment. The enhanced osteogenic potential of these daidzein analogs resulted in increased osterix (Sp7), alkaline phosphatase (ALP), osteopontin (OPN), and insulin-like growth factor 1 (IGF-1), which are osteogenic transcription factors that regulate the maturation of osteogenic progenitor cells into mature osteoblast cells.

  DOI：

  10.1021/ml400397k
• 作为产物：
  描述：

  1,1-二乙氧基-3-甲基-2-丁烯 在 3-甲基吡啶 、 palladium on activated charcoal 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 5,5-dimethyl-1,3-cyclohexadiene 、 水 为溶剂， 反应 25.0h， 生成 3-(4-hydroxyphenyl)-8,8-dimethyl-4H,8H-pyrano[2,3-f]chromen-4-one
  参考文献：
  名称：

  高选择性基于氨基甲酸酯的丁酰胆碱酯酶抑制剂，其源自天然存在的吡喃异黄酮。

  摘要：

  这项当前的研究描述了一系列基于天然吡喃异黄酮的衍生物的设计和合成，该衍生物是从粟米草的种子中获得的，在我们之前的研究中显示出有吸引力的BChE抑制作用和高选择性。评价了所有衍生物对两种胆碱酯酶的抑制潜力。只有少数化合物在测试浓度下显示出AChE抑制活性，而26种化合物显示出对BChE的显着抑制作用（IC50值从9.34μM到0.093μM不等），其中大多数对BChE病区具有选择性。预测了7种活性最高的化合物的ADME性质。其中9g（IC50 = 222 nM）和9h（IC50 = 93 nM）被发现是最有效的BChE抑制剂，对AChE的选择性极好（SI比分别为1339和836）。动力学分析表明它们都充当混合型BChE抑制剂，而分子对接结果表明它们与催化活性位点的两个残基都相互作用。对PC12细胞的细胞毒性测试表明，9g和9h的治疗安全范围均与他克林相似。总体而言，结果表明9h可能是BChE抑制剂的良好候选者。

  DOI：

  10.1016/j.bioorg.2019.102949

文献信息

• Daidzein analogs as treatment for cancer
  申请人：THE ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND

  公开号：US09669004B2

  公开（公告）日：2017-06-06

  Provided are compositions for treatment of cancers, including breast cancer, comprising at least one novel daidzein analog, as well as methods of using the same for preventing or treating cancer or tumor growth.

  提供了用于治疗癌症的组合物，包括至少一种新型的大豆异黄酮类似物，以及使用它们预防或治疗癌症或肿瘤生长的方法。
• Enhanced Osteogenic Activity of Daidzein Analogs on Human Mesenchymal Stem Cells
  申请人：THE ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND

  公开号：US20160068542A1

  公开（公告）日：2016-03-10

  Disclosed are daidzein analogs having the formula (I). Also disclosed are compositions, include a disclosed daidzein analogs, methods of preventing or treating bone disease or bone injury and/or stimulating bone growth, in a subject that include administering to the subject an effective amount of disclosed daidzein analog. Disclosed are isolated mesenchymal stem cell that has been altered by treatment a disclosed daidzein analog, daidzein, glycinol, glyceollin I, or glyceollin II, to increase the osteogenic potential of the mesenchymal stem cells.

  本发明揭示了具有公式（I）的daidzein类似物。还揭示了包括所述daidzein类似物的组合物，用于预防或治疗骨疾病或骨损伤和/或刺激骨生长的方法，包括向受体施用揭示的daidzein类似物的有效量。本发明揭示了已通过处理揭示的daidzein类似物，daidzein，glycinol，glyceollin I或glyceollin II而改变的分离的间充质干细胞，以增加间充质干细胞的成骨潜能。
• Synthesis, structure–activity relationships and biological evaluation of barbigerone analogues as anti-proliferative and anti-angiogenesis agents
  作者：Guangcheng Wang、Fang Wang、Dong Cao、Yibin Liu、Ronghong Zhang、Haoyu Ye、Xiuxia Li、Lin He、Zhuang Yang、Liang Ma、Aihua Peng、Mingli Xiang、Yuquan Wei、Lijuan Chen

  DOI：10.1016/j.bmcl.2014.04.121

  日期：2014.7

  A series of barbigerone analogues (7a-7w, 13a-13x) were designed, synthesized and biologically evaluated for their anti-proliferative and anti-angiogenic activities. Among these compounds, compound 13a exhibited the most potent inhibitory effect on the proliferation of HUVECs, HepG2, A375, U251, B16, and HCT116 cells (IC50 = 3.80, 0.28, 1.58, 3.50, 1.09 and 0.68 mu M, respectively). Compound 13a inhibited the angiogenesis in zebrafish embryo assay in a concentration-dependent manner. Furthermore, 13a also effectively inhibited the migration and capillary like tube formation of human umbilical vein endothelial cell in vitro. These results support the further investigation of this class of compounds as potential anti-proliferative and anti-angiogenesis agents. (C) 2014 Published by Elsevier Ltd.
• [EN] ENHANCED OSTEOGENIC ACTIVITY OF DAIDZEIN ANALOGS ON HUMAN MESENCHYMAL STEM CELLS<br/>[FR] ACTIVITÉ OSTÉOGÉNIQUE ACCRUE D'ANALOGUES DE LA DAIDZÉINE SUR LES CELLULES SOUCHES MÉSENCHYMATEUSES HUMAINES
  申请人：UNIV TULANE

  公开号：WO2014165723A3

  公开（公告）日：2014-12-31
• Effects of 7-O Substitutions on Estrogenic and Anti-Estrogenic Activities of Daidzein Analogues in MCF-7 Breast Cancer Cells
  作者：Quan Jiang、Florastina Payton-Stewart、Steven Elliott、Jennifer Driver、Lyndsay V. Rhodes、Qiang Zhang、Shilong Zheng、Deepak Bhatnagar、Stephen M. Boue、Bridgette M. Collins-Burow、Jayalakshmi Sridhar、Cheryl Stevens、John A. McLachlan、Thomas E. Wiese、Matthew E. Burow、Guangdi Wang

  DOI：10.1021/jm100610w

  日期：2010.8.26

  Daidzein (1) is a natural estrogenic isoflavone. We report here that 1 can be transformed into anti-estrogenic ligands by simple alkyl substitutions of the 7-hydroxyl hydrogen. To test the effect of such structural modifications on the hormonal activities of the resulting compounds, a series of daidzein analogues have been designed and synthesized. When MCF-7 cells were treated with the analogues, those resulting from hydrogen substitution by isopropyl (3d), isobutyl (3f), cyclopentyl (3g), and pyrano- (2) inhibited cell proliferation, estrogen-induced transcriptional activity, and estrogen receptor (ER) regulated progesterone receptor (PgR) gene expression. However, methyl (3a) and ethyl (3b) substitutions of the hydroxyl proton only led to moderate reduction of the estrogenic activities. These results demonstrated the structural requirements for the transformation of daidzein from an ER agonist to an antagonist. The most effective analogue, 2, was found to reduce in vivo estrogen stimulated MCF-7 cell tumorigenesis using a xenograft mouse model.