3,17β-bis-(2-tetrahydropyranyloxy)-7α-(6-hydroxyhexan-1-yl)-estra-1,3,5(10)-triene | 408512-83-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 3,17β-bis-(2-tetrahydropyranyloxy)-7α-(6-hydroxyhexan-1-yl)-estra-1,3,5(10)-triene
• 英文别名: 6-[(7R,8R,9S,13S,14S,17S)-13-methyl-3,17-bis(oxan-2-yloxy)-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-7-yl]hexan-1-ol
• CAS: 408512-83-4
• 化学式: C₃₄H₅₂O₅
• 分子量: 540.784
• InChiKey: BLQYPTOXUHRYFK-WRCDNKAVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.9
• 重原子数：
  39
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  57.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3,17β-bis-(2-tetrahydropyranyloxy)-7α-(6-hydroxyhexan-1-yl)-estra-1,3,5(10)-triene 在 四丁基氟化铵 、 四丁基溴化铵 、 sodium hydride 、 N,N-二异丙基乙胺 、 lithium bromide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 2.0h， 生成
  参考文献：
  名称：

  A Rationally Designed Genotoxin that Selectively Destroys Estrogen Receptor-Positive Breast Cancer Cells

  摘要：

  We describe a novel strategy to increase the selective toxicity of genotoxic compounds. The strategy involves the synthesis of bifunctional molecules capable of forming DNA adducts that have high affinity for specific proteins in target cells. It is proposed that the association of such proteins with damaged sites in DNA can compromise protein function and/or DNA repair resulting in increased toxicity. We describe the synthesis of a bifunctional compound consisting of an aniline mustard linked to the 7alpha position of estradiol. This novel compound can form covalent DNA adducts that have high affinity for the estrogen receptor. Breast cancer cells that express high levels of the estrogen receptor showed increased sensitivity to the cytotoxic effects of the new compound.

  DOI：

  10.1021/ja017344p
• 作为产物：
  描述：

  雌二醇 在 三乙基硅烷 、 三乙基硼 、 三氟化硼乙醚 、 硼烷 、 potassium tert-butylate 、 4-甲基苯磺酸吡啶 、 乙酰氯 、 pyridinium chlorochromate 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 正己烷 、 二氯甲烷 为溶剂， 反应 43.83h， 生成 3,17β-bis-(2-tetrahydropyranyloxy)-7α-(6-hydroxyhexan-1-yl)-estra-1,3,5(10)-triene
  参考文献：
  名称：

  A Rationally Designed Genotoxin that Selectively Destroys Estrogen Receptor-Positive Breast Cancer Cells

  摘要：

  We describe a novel strategy to increase the selective toxicity of genotoxic compounds. The strategy involves the synthesis of bifunctional molecules capable of forming DNA adducts that have high affinity for specific proteins in target cells. It is proposed that the association of such proteins with damaged sites in DNA can compromise protein function and/or DNA repair resulting in increased toxicity. We describe the synthesis of a bifunctional compound consisting of an aniline mustard linked to the 7alpha position of estradiol. This novel compound can form covalent DNA adducts that have high affinity for the estrogen receptor. Breast cancer cells that express high levels of the estrogen receptor showed increased sensitivity to the cytotoxic effects of the new compound.

  DOI：

  10.1021/ja017344p

文献信息

• Prodigiosenes conjugated to tamoxifen and estradiol
  作者：Estelle Marchal、Carlotta Figliola、Alison Thompson

  DOI：10.1039/c7ob00943g

  日期：——

  We report the synthesis of the first click-appended prodigiosene conjugates. Four prodigiosene conjugates of estradiol functionalised at the 7α-position were prepared, as were three prodigiosene conjugates of tamoxifen. The coupling between a prodigiosene and an 11-hydroxy estradiol derivative via an ether linkage was investigated, as was the 11- and 7-functionalisation of the estradiol core. The robustness

  我们报告的第一个单击追加prodigiosene共轭物的合成。制备了在7α-位官能化的四种雌二醇的前黄花共轭物，以及他莫昔芬的三种前黄花共轭物。dig和11-羟基雌二醇衍生物之间的偶联通过研究了醚键，以及雌二醇核心的11-和7-官能化。雌二醇保护基团的稳健性受到通常用于为11和7官能化的这类骨架装备的反应的严峻挑战。特别是，对于涉及雌二醇的合成而言，TBS，TMS和THP对合成至关重要，对于该核心的功能化而言，它不是有用的保护基。当治疗剂的化学特征限制了保护基团的选择（在这种情况下，带有芳基，NH，烯基和酯基的pro二烯），点击化学就成为一种有吸引力的合成策略。评估了七种单击的前黄酮共轭物的抗癌活性。
• Methods and compositions for treating cancer
  申请人：Eissigmann M. John

  公开号：US20060019936A1

  公开（公告）日：2006-01-26

  The invention provides compounds and methods for treating cancer. Exemplary compounds are multi-functional compounds with two different moieties connected by a linker. Compounds of the invention can activate one or more pathways that result in the inhibition of cell growth. The invention includes cytostatic and cytotoxic compounds. Methods and compositions of the invention are particularly useful for treating cancer cells that are resistant to other chemotherapeutic drugs.

  这项发明提供了用于治疗癌症的化合物和方法。示例化合物是具有两种不同基团通过连接剂连接的多功能化合物。该发明的化合物可以激活导致细胞生长抑制的一个或多个途径。该发明包括细胞静止和细胞毒性化合物。该发明的方法和组合物特别适用于治疗对其他化疗药物具有抗药性的癌细胞。
• Design, synthesis, and evaluation of estradiol-linked genotoxicants as anti-cancer agents
  作者：U Sharma、J.C Marquis、A Nicole Dinaut、S.M Hillier、B Fedeles、P.T Rye、J.M Essigmann、R.G Croy

  DOI：10.1016/j.bmcl.2004.04.064

  日期：2004.7

  A series of bifunctional compounds was prepared consisting of 17beta estradiol linked to a DNA damaging N,N-bis-(2-chloroethyl)aniline. The objective of our studies was to determine the characteristics of the linker that permitted both reaction with DNA and binding of the resultant covalent adducts to the estrogen receptor. Linker characteristics were pivotal determinants underlying the ability of the compounds to kill selectively breast cancer cells that express the estrogen receptor. (C) 2004 Elsevier Ltd. All rights reserved.
• A Rationally Designed Genotoxin that Selectively Destroys Estrogen Receptor-Positive Breast Cancer Cells
  作者：Kaushik Mitra、John C. Marquis、Shawn M. Hillier、Peter T. Rye、Beatriz Zayas、Annie S. Lee、John M. Essigmann、Robert G. Croy

  DOI：10.1021/ja017344p

  日期：2002.3.1

  We describe a novel strategy to increase the selective toxicity of genotoxic compounds. The strategy involves the synthesis of bifunctional molecules capable of forming DNA adducts that have high affinity for specific proteins in target cells. It is proposed that the association of such proteins with damaged sites in DNA can compromise protein function and/or DNA repair resulting in increased toxicity. We describe the synthesis of a bifunctional compound consisting of an aniline mustard linked to the 7alpha position of estradiol. This novel compound can form covalent DNA adducts that have high affinity for the estrogen receptor. Breast cancer cells that express high levels of the estrogen receptor showed increased sensitivity to the cytotoxic effects of the new compound.