1,1-双(4-羟基苯基)-2-苯基丁-1-烯 | 91221-46-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 中文名称: 1,1-双(4-羟基苯基)-2-苯基丁-1-烯
• 中文别名: 1,1-双(4-羟基苯基)-2-苯基-1-丁烯
• 英文名称: 1,1-bis(4-hydroxyphenyl)-2-phenyl-1-butene
• 英文别名: 1,1-bis(4-hydroxyphenyl)-2-phenylbut-1-ene；4,4'-(2-phenylbut-1-ene-1,1-diyl)diphenol；4-[1-(4-hydroxyphenyl)-2-phenylbut-1-enyl]phenol
• CAS: 91221-46-4
• 化学式: C₂₂H₂₀O₂
• 分子量: 316.4
• InChiKey: BPKSDMHGDYTXLI-UHFFFAOYSA-N

物化性质

• 熔点：
  202°C(lit.)
• 沸点：
  457.7±35.0 °C(Predicted)
• 密度：
  1.161±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• 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

安全信息

• 储存条件：
  室温下，保存在惰性气体中。

反应信息

• 作为反应物：
  描述：

  1,1-双(4-羟基苯基)-2-苯基丁-1-烯 在 吡啶 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium hydrogen difluoride 、 potassium acetate 、 caesium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.17h， 生成 potassium (4-(1-(4-(2-(dimethylamino)ethoxy)phenyl)-2-phenylbut-1-en-1-yl)phenyl) trifluoroborate
  参考文献：
  名称：

  Boron-Based 4-Hydroxytamoxifen Bioisosteres for Treatment of de Novo Tamoxifen Resistant Breast Cancer

  摘要：

  Tamoxifen remains the first line therapy for estrogen receptor positive (ER+) breast cancer. However, polymorphisms of the gene encoding P450 2D6 could result in no protein expression or no CYP2D6 enzymatic activity and may significantly reduce the benefit of the hormone therapy. To address this issue, we designed and synthesized three 4-hydroxytamoxifen bioisosteres utilizing a boron-aryl carbon bond that can be oxidized under physiological conditions to yield 4-hydroxytamoxifen. We show that the bioisosteres inhibit the growth of two ER+ breast cancer cell lines, MCF-7 and T47D, with potencies comparable to or greater than that of 4-hydroxytamoxifen. We further demonstrate that after incubation with breast cancer cells, the majority of the bioisosteres has been converted to 4-hydroxytamoxifen. Our study suggests that boron-based 4-hydroxytamoxifen bioisosteres may be an effective therapeutic remedy for intrinsic tamoxifen resistance in breast cancer patients deficient in CYP2D6 metabolism.

  DOI：

  10.1021/ml3000287
• 作为产物：
  描述：

  E/Z-1-(4-hydroxyphenyl)-1-(4-methoxyphenyl)-2-phenylbutene 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以86%的产率得到1,1-双(4-羟基苯基)-2-苯基丁-1-烯
  参考文献：
  名称：

  Synthesis of the new pseudo-symmetrical tamoxifen derivatives and their anti-tumor activity

  摘要：

  Three new pseudo-symmetrical tamoxifen derivatives, RID-B (15), C (16), and D (17), were synthesized via the novel three-component coupling reaction, and the structure-activity relationships of the pseudo-symmetrical tamoxifen derivatives were examined. It was discovered that 15 strongly inhibits the viability of HL-60 human acute promyelocytic leukemia, whereas 16 possesses medium activity against the cell line and 17 has no effect on the cell viability. The agarose gel electrophoresis for DNA cleavage showed the cell death might be induced by apoptosis. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.02.037

文献信息

• [EN] TETRASUBSTITUTED ALKENE COMPOUNDS AND THEIR USE<br/>[FR] COMPOSÉS ALCÉNIQUES TÉTRASUBSTITUÉS ET LEUR UTILISATION
  申请人：EISAI R&D MAN CO LTD

  公开号：WO2016196342A1

  公开（公告）日：2016-12-08

  Disclosed herein are compounds, or pharmaceutically acceptable salts thereof, and methods of using the compounds for treating breast cancer by administration to a subject in need thereof a therapeutically effective amount of the compounds or pharmaceutically acceptable salts thereof. The breast cancer may be an ER-positive breast cancer and/or the subject in need of treatment may express a mutant ER-α protein.

  本文披露了化合物或其药用可接受盐，并使用这些化合物治疗乳腺癌的方法，通过向需要治疗的受试者施用这些化合物或其药用可接受盐的治疗有效量。乳腺癌可能是ER阳性乳腺癌，需要治疗的受试者可能表达突变的ER-α蛋白。
• [EN] BORON-BASED 4-HYDROXYTAMOXIFEN AND ENDOXIFEN PRODRUGS AS TREATMENT FOR BREAST CANCER<br/>[FR] PROMÉDICAMENTS DE 4-HYDROXYTAMOXIFÈNE ET D'ENDOXIFÈNE À BASE DE BORE UTILISÉS COMME TRAITEMENT POUR LE CANCER DU SEIN
  申请人：XAVIER UNIVERSITY

  公开号：WO2013134230A1

  公开（公告）日：2013-09-12

  The present disclosure relates to boron-based 4-hydroxytamoxifen and endoxifen prodrugs and the synthesis of the same. Further, the present disclosure teaches the utilization of the boron- based 4-hydroxytamoxifen and endoxifen prodrugs in a treatment for breast cancer.

  本公开涉及基于硼的4-羟基他莫昔芬和内酰胺前药以及它们的合成。此外，本公开教导了利用基于硼的4-羟基他莫昔芬和内酰胺前药治疗乳腺癌。
• [EN] ESTROGEN RECEPTOR TARGETING ANTAGONISTS<br/>[FR] ANTAGONISTES CIBLANT LE RÉCEPTEUR DES OESTROGÈNES
  申请人：XAVIER UNIV OF LOUISIANA

  公开号：WO2020055973A1

  公开（公告）日：2020-03-19

  The present disclosure relates to compounds that act as antagonists via binding to the ER ligand binding domain non-covalently or covalently, or act as both antagonists and ER protein degraders, and the synthesis of the same. Further, the present disclosure teaches the utilization of such compounds in a treatment for proliferative diseases, including cancer, particularly breast cancer, and especially ER+ breast cancer.

  本公开涉及通过非共价或共价结合到ER配体结合结构域的化合物，作为拮抗剂或同时作为拮抗剂和ER蛋白降解剂，并且涉及这些化合物的合成。此外，本公开教导了利用这些化合物治疗增殖性疾病，包括癌症，特别是乳腺癌，尤其是ER+乳腺癌。
• NOVEL COMPOUNDS HAVING ESTROGEN RECEPTOR ALPHA DEGRADATION ACTIVITY AND USES THEREOF
  申请人：ACCUTAR BIOTECHNOLOGY INC.

  公开号：US20200157078A1

  公开（公告）日：2020-05-21

  The present disclosure relates to novel compounds having estrogen receptor alpha degradation activity, pharmaceutical compositions containing such compounds, and their use in prevention and treatment of cancer and related diseases and conditions.

  本公开涉及具有雌激素受体α降解活性的新化合物，包含这些化合物的药物组合物，以及它们在预防和治疗癌症及相关疾病和症状中的应用。
• A new Suzuki synthesis of triphenylethylenes that inhibit aromatase and bind to estrogen receptors α and β
  作者：Li-Ming Zhao、Hai-Shan Jin、Jinzhong Liu、Todd C. Skaar、Joseph Ipe、Wei Lv、David A. Flockhart、Mark Cushman

  DOI：10.1016/j.bmc.2016.08.064

  日期：2016.11

  The design and synthesis of dual aromatase inhibitors/selective estrogen receptor modulators (AI/SERMs) is an attractive strategy for the discovery of new breast cancer therapeutic agents. Previous efforts led to the preparation of norendoxifen (4) derivatives with dual aromatase inhibitory activity and estrogen receptor binding activity. In the present study, some of the structural features of the

  双芳香酶抑制剂/选择性雌激素受体调节剂（AI / SERM）的设计与合成是发现新型乳腺癌治疗剂的一种有吸引力的策略。先前的努力导致制备了具有双重芳香酶抑制活性和雌激素受体结合活性的去甲多芬（4）衍生物。在本研究中，强力的甲硝唑的一些结构特征被掺入了先导化合物（诺伦多芬）中，从而提供了一系列基于对称的二苯基亚甲基亚结构的新型双重AI / SERM药剂，从而消除了E，Z异构化的问题。基于Norendoxifen的AI / SERM遇到的问题。化合物12d具有良好的芳香化酶抑制活性（IC 50 ＝ 62.2nM），同时还表现出对ER-α（EC 50  ＝ 72.1nM）和ER-β（EC 50  ＝ 70.8nM）的良好结合活性。此外，还设计了一种新的合成方法，用于通过bis-Suzuki偶联策略制备去甲诺昔芬及其类似物。