N,N-dimethyl-2-(4-(2-phenyl-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)but-1-en-1-yl)phenoxy)ethanamine | 1370699-81-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: N,N-dimethyl-2-(4-(2-phenyl-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)but-1-en-1-yl)phenoxy)ethanamine
• 英文别名: N,N-dimethyl-2-[4-[2-phenyl-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]but-1-enyl]phenoxy]ethanamine
• CAS: 1370699-81-2
• 化学式: C₃₂H₄₀BNO₃
• 分子量: 497.485
• InChiKey: VUXAWPQCXOUQMJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  30.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N,N-dimethyl-2-(4-(2-phenyl-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)but-1-en-1-yl)phenoxy)ethanamine 在 potassium hydrogen difluoride 作用下， 以 甲醇 、 水 为溶剂， 反应 0.25h， 以65%的产率得到potassium (4-(1-(4-(2-(dimethylamino)ethoxy)phenyl)-2-phenylbut-1-en-1-yl)phenyl) trifluoroborate
  参考文献：
  名称：

  [EN] BORON-BASED 4-HYDROXYTAMOXIFEN AND ENDOXIFEN PRODRUGS AS TREATMENT FOR BREAST CANCER
  [FR] PROMÉDICAMENTS DE 4-HYDROXYTAMOXIFÈNE ET D'ENDOXIFÈNE À BASE DE BORE UTILISÉS COMME TRAITEMENT POUR LE CANCER DU SEIN

  摘要：

  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。

  公开号：

  WO2013134230A1
• 作为产物：
  描述：

  阿非昔芬 在 吡啶 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 N,N-dimethyl-2-(4-(2-phenyl-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)but-1-en-1-yl)phenoxy)ethanamine
  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

文献信息

• [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。
• Boron-Based 4-Hydroxytamoxifen Bioisosteres for Treatment of de Novo Tamoxifen Resistant Breast Cancer
  作者：Quan Jiang、Qiu Zhong、Qiang Zhang、Shilong Zheng、Guangdi Wang

  DOI：10.1021/ml3000287

  日期：2012.5.10

  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.