3,17β-bis(2-tetrahydropyranyloxy)-7α-(5-hexen-1-yl)-estra-1,3,5(10)-triene-6-one | 251322-01-7

• 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-(5-hexen-1-yl)-estra-1,3,5(10)-triene-6-one
• 英文别名: 3,17β-bis(2-tetrahydropyranyloxy)-7α-(5-hexen-1-yl)estra-1,3,5(10)-triene-6-one；(7S,8R,9S,13S,14S,17S)-7-hex-5-enyl-13-methyl-3,17-bis(oxan-2-yloxy)-8,9,11,12,14,15,16,17-octahydro-7H-cyclopenta[a]phenanthren-6-one
• CAS: 251322-01-7
• 化学式: C₃₄H₄₈O₅
• 分子量: 536.752
• InChiKey: QKYCFMNLRMXERC-YJDJXLSXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8
• 重原子数：
  39
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3,17β-bis(2-tetrahydropyranyloxy)-7α-(5-hexen-1-yl)-estra-1,3,5(10)-triene-6-one 在 三乙基硅烷 、 三氟化硼乙醚 、 硼烷 、 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 、 lithium bromide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 37.0h， 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
• 作为产物：
  描述：

  雌二醇 在 三乙基硼 、 potassium tert-butylate 、 4-甲基苯磺酸吡啶 、 pyridinium chlorochromate 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 、 二氯甲烷 为溶剂， 反应 11.83h， 生成 3,17β-bis(2-tetrahydropyranyloxy)-7α-(5-hexen-1-yl)-estra-1,3,5(10)-triene-6-one
  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

• Synthesis and Binding Affinities of Novel Re-Containing 7α-Substituted Estradiol Complexes:  Models for Breast Cancer Imaging Agents
  作者：Marc B. Skaddan、Frank R. Wüst、John A. Katzenellenbogen

  DOI：10.1021/jo990641g

  日期：1999.10.1

  rhenium metal involve "3 + 1" and "4 + 1" mixed ligand complexes (2a-c and 5, respectively), tricarbonyl dithioether complexes (3), and the cyclopentadienyltricarbonylmetal organometallic system (4ab, 6, 7). These complexes showed binding affinities for the estrogen receptor (as high as 45% for the "3 + 1" complex 2c) when compared to the native ligand estradiol. The polarity of some complexes (4ab) was modified

  乳腺癌的诊断和分期可以通过影像学放射性药物的开发来改善，该成像药物可以无创地确定肿瘤细胞中雌激素受体的状态。为了实现这一目标，我们合成了许多新型的含Re的7α-取代的雌二醇复合物。7α侧链的引入涉及四氢吡喃氧基保护的6-酮雌二醇的烷基化。引入metal金属的方法包括“ 3 +1”和“ 4 +1”混合配体配合物（分别为2a-c和5），三羰基二硫醚配合物（3）和环戊二烯基三羰基金属有机金属体系（4ab，6）。 7）。这些复合物显示出对雌激素受体的结合亲和力（“ 3 +1”的亲和力高达45％与天然的配体雌二醇相比，复合物2c）。通过将（聚）醚键引入7alpha侧链（6，7），对某些复合物（4ab）的极性进行了修饰，以改善生物分布特性。这些复合物为我们对雌激素受体的配体结构-结合亲和力相关性的理解提供了进一步的完善，并且为合成类似的Tc-99m复合物作为乳腺肿瘤成像剂进行评估提供了合成基础。
• Skaddan; Wust; Welch, Journal of labelled compounds and radiopharmaceuticals, 1999, vol. 42, # SUPPL. 1, p. S153-S155
  作者：Skaddan、Wust、Welch、Katzenellenbogen

  DOI：——

  日期：——
• 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.