4,4'-((2,3-dihydro-1H-inden-1-ylidene)methylene)diphenol

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4,4'-((2,3-dihydro-1H-inden-1-ylidene)methylene)diphenol
• 英文别名: 4-[2,3-Dihydroinden-1-ylidene-(4-hydroxyphenyl)methyl]phenol
• 化学式: C₂₂H₁₈O₂
• 分子量: 314.384
• InChiKey: SWVJYVYEZKEVIL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  40.5
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4,4'-((2,3-dihydro-1H-inden-1-ylidene)methylene)diphenol 在 aluminum (III) chloride 、 lithium aluminium tetrahydride 、 potassium carbonate 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 4.17h， 生成 4-((4-(2-aminoethoxy)phenyl)(2,3-dihydro-1H-inden-1-ylidene)methyl)phenol
  参考文献：
  名称：

  Design and Synthesis of Norendoxifen Analogues with Dual Aromatase Inhibitory and Estrogen Receptor Modulatory Activities

  摘要：

  Both selective estrogen receptor modulators and aromatase inhibitors are widely used for the treatment of breast cancer. Compounds with both aromatase inhibitory and estrogen receptor modulatory activities could have special advantages for treatment of breast cancer. Our previous efforts led to the discovery of norendoxifen as the first compound with dual aromatase inhibitory and estrogen receptor binding activities. To optimize its efficacy and aromatase selectivity versus other cytochrome P450 enzyme, a series of structurally related norendoxifen analogues were designed and synthesized. The most potent compound, 4'-hydroxynorendoxifen (10), displayed elevated inhibitory potency against aromatase and enhanced affinity for estrogen receptors when compared to norendoxifen. The selectivity of 10 for aromatase versus other cytochrome P450 eniymes was also superior to norendoxifen. 4'-Hydroxynorendoxifen is therefore an interesting lead for further development to obtain new anticancer agents of potential value for the treatment of breast cancer.

  DOI：

  10.1021/jm501218e
• 作为产物：
  描述：

  1-[bis(4-methoxyphenyl)methylidenyl]indane 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 以82%的产率得到4,4'-((2,3-dihydro-1H-inden-1-ylidene)methylene)diphenol
  参考文献：
  名称：

  Triarylethylene bisphenols with a novel cycle are ligands for the estrogen receptor

  摘要：

  We have prepared a series of triarylethylene and triarylethane systems, analogues of the selective antiestrogen tamoxifen, in which the alkyl substituent is tethered to the distal, rather than the proximal aryl ring by a 5-, 6-, or 7-membered carbocycle. This unusual cyclic structure rigidifies the ligand and adds bulk in a manner that is different from the more typical cyclization to the proximal aryl ring, as in the antiestrogen nafoxidine. These new systems were prepared efficiently by the addition of a benzylic sodium reagent, generated fi om the corresponding chloride by treatment with sodium naphthalenide, to a doubly protected 4,4'-dihydroxybenzophenone, followed by dehydration and deprotection. In all cases, formation of the exocyclic alkene was preferred. Two of the corresponding alkanes could be obtained by catalytic hydrogenation. All of these compounds have relatively high binding affinity for the estrogen receptor, and some of them demonstrate a significant level of affinity selectivity for the estrogen receptor alpha subtype. Accommodation of these newly rigidified cyclic triarylethylene systems into the ligand-binding pocket of the estrogen receptor can be visualized by molecular modeling. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00016-x

文献信息

• Synthesis and SAR Analysis of Novel 4-Hydroxytamoxifen Analogues Based on Their Cytotoxic Activity and Electron-Donor Character
  作者：Cintia Duró、Tamás Jernei、Krisztina J. Szekeres、Győző G. Láng、Rita Oláh-Szabó、Szilvia Bősze、Ildikó Szabó、Ferenc Hudecz、Antal Csámpai

  DOI：10.3390/molecules27196758

  日期：——

  Utilizing McMurry reactions of 4,4′-dihydroxybenzophenone with appropriate carbonyl compounds, a series of 4-Hydroxytamoxifen analogues were synthesized. Their cytotoxic activity was evaluated in vitro on four human malignant cell lines (MCF-7, MDA-MB 231, A2058, HT-29). It was found that some of these novel Tamoxifen analogues show marked cytotoxicity in a dose-dependent manner. The relative ROS-generating

  利用4,4'-二羟基二苯甲酮与适当的羰基化合物的McMurry反应，合成了一系列4-羟基他莫昔芬类似物。在四种人类恶性细胞系（MCF-7、MDA-MB 231、A2058、HT-29）上体外评估了它们的细胞毒活性。发现这些新型他莫昔芬类似物中的一些以剂量依赖性方式显示出显着的细胞毒性。通过循环伏安法 (CV) 和 DFT 建模研究评估了合成类似物的相对 ROS 生成能力。细胞活力测定、CV测量和DFT计算的结果表明，大多数新型化合物的细胞毒性主要是由它们与包括雌激素受体在内的细胞靶标的相互作用引起的，而不是由氧化还原过程触发的。然而，三种新化合物可能参与ROS的产生和随后醌甲基化物的形成，从而防止增殖并破坏处理细胞的氧化还原平衡。在所研究的细胞系中，HT-29 被证明对具有 ROS 生成能力的化合物的处理最敏感。
• Design and Synthesis of Norendoxifen Analogues with Dual Aromatase Inhibitory and Estrogen Receptor Modulatory Activities
  作者：Wei Lv、Jinzhong Liu、Todd C. Skaar、David A. Flockhart、Mark Cushman

  DOI：10.1021/jm501218e

  日期：2015.3.26

  Both selective estrogen receptor modulators and aromatase inhibitors are widely used for the treatment of breast cancer. Compounds with both aromatase inhibitory and estrogen receptor modulatory activities could have special advantages for treatment of breast cancer. Our previous efforts led to the discovery of norendoxifen as the first compound with dual aromatase inhibitory and estrogen receptor binding activities. To optimize its efficacy and aromatase selectivity versus other cytochrome P450 enzyme, a series of structurally related norendoxifen analogues were designed and synthesized. The most potent compound, 4'-hydroxynorendoxifen (10), displayed elevated inhibitory potency against aromatase and enhanced affinity for estrogen receptors when compared to norendoxifen. The selectivity of 10 for aromatase versus other cytochrome P450 eniymes was also superior to norendoxifen. 4'-Hydroxynorendoxifen is therefore an interesting lead for further development to obtain new anticancer agents of potential value for the treatment of breast cancer.
• Triarylethylene bisphenols with a novel cycle are ligands for the estrogen receptor
  作者：Sung-Hoon Kim、John A. Katzenellenbogen

  DOI：10.1016/s0968-0896(00)00016-x

  日期：2000.4

  We have prepared a series of triarylethylene and triarylethane systems, analogues of the selective antiestrogen tamoxifen, in which the alkyl substituent is tethered to the distal, rather than the proximal aryl ring by a 5-, 6-, or 7-membered carbocycle. This unusual cyclic structure rigidifies the ligand and adds bulk in a manner that is different from the more typical cyclization to the proximal aryl ring, as in the antiestrogen nafoxidine. These new systems were prepared efficiently by the addition of a benzylic sodium reagent, generated fi om the corresponding chloride by treatment with sodium naphthalenide, to a doubly protected 4,4'-dihydroxybenzophenone, followed by dehydration and deprotection. In all cases, formation of the exocyclic alkene was preferred. Two of the corresponding alkanes could be obtained by catalytic hydrogenation. All of these compounds have relatively high binding affinity for the estrogen receptor, and some of them demonstrate a significant level of affinity selectivity for the estrogen receptor alpha subtype. Accommodation of these newly rigidified cyclic triarylethylene systems into the ligand-binding pocket of the estrogen receptor can be visualized by molecular modeling. (C) 2000 Elsevier Science Ltd. All rights reserved.