7α-[6-(N-(2-(tert-butyldimethylsilanyloxy)-ethyl)-diphenylphosphinamido)-hexan-1-yl]-estra-1,3,5(10)triene-3,17β-bis-2-tetrahydropyranyl ether | 408512-85-6

• 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: 7α-[6-(N-(2-(tert-butyldimethylsilanyloxy)-ethyl)-diphenylphosphinamido)-hexan-1-yl]-estra-1,3,5(10)triene-3,17β-bis-2-tetrahydropyranyl ether
• 英文别名: N-[2-[tert-butyl(dimethyl)silyl]oxyethyl]-N-diphenylphosphoryl-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-amine
• CAS: 408512-85-6
• 化学式: C₅₄H₈₀NO₆PSi
• 分子量: 898.292
• InChiKey: CDDURZQVKUWEGO-WJXNKPKVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.79
• 重原子数：
  63
• 可旋转键数：
  19
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  66.5
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  7α-[6-(N-(2-(tert-butyldimethylsilanyloxy)-ethyl)-diphenylphosphinamido)-hexan-1-yl]-estra-1,3,5(10)triene-3,17β-bis-2-tetrahydropyranyl ether 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 生成 7α-[6-(N-(2-hydroxyethyl)-diphenylphosphinamido)-hexan-1-yl]-estra-1,3,5(10)triene-3,17β-bis-2-tetrahydropyranyl ether
  参考文献：
  名称：

  Design, synthesis, and evaluation of estradiol-linked genotoxicants as anti-cancer agents

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2004.04.064
• 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 、 四丁基溴化铵 、 4-甲基苯磺酸吡啶 、 sodium hydride 、 N,N-二异丙基乙胺 、 乙酰氯 、 pyridinium chlorochromate 、 lithium bromide 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 48.83h， 生成 7α-[6-(N-(2-(tert-butyldimethylsilanyloxy)-ethyl)-diphenylphosphinamido)-hexan-1-yl]-estra-1,3,5(10)triene-3,17β-bis-2-tetrahydropyranyl ether
  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

• 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.
• 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.