17β-tert-butyldimethylsilyloxy-3-hydroxyestra-1,3,5(10)-trien-2-carboxaldehyde | 208758-19-4

• 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: 17β-tert-butyldimethylsilyloxy-3-hydroxyestra-1,3,5(10)-trien-2-carboxaldehyde
• 英文别名: 17beta-Tert-butyldimethylsilyloxy-3-hydroxyestra-1,3,5(10)-triene-2-carboxaldehyde；(8R,9S,13S,14S,17S)-17-[tert-butyl(dimethyl)silyl]oxy-3-hydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-2-carbaldehyde
• CAS: 208758-19-4
• 化学式: C₂₅H₃₈O₃Si
• 分子量: 414.66
• InChiKey: YQPJMGZSDLINNX-VBAOBDAXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.45
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  17β-tert-butyldimethylsilyloxy-3-hydroxyestra-1,3,5(10)-trien-2-carboxaldehyde 在 sodium tetrahydroborate 、 sodium hydride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 生成 17β-hydroxyestra-1,3,5(10)-trien-[3,2,e]-3',4'-dihydro-1',2',3'-oxathiazine-2',2'-dioxide
  参考文献：
  名称：

  Steroidal oxathiazine inhibitors of estrone sulfatase

  摘要：

  The presence of estrone sulfatase in breast tumors and the high levels of circulating estrone sulfate may contribute the major portion of estrogen synthesized locally in breast tissues through conversion of estrone sulfate to estrone by the enzyme. Using inhibitors of estrone sulfatase for the treatment of estrogen-dependent (estrogen receptor positive, ER+) breast cancer could be a very effective therapeutic strategy for the treatment of estrogen-dependent breast tumors in postmenopausal women. Therefore, we designed and synthesized several steroidal 2',3-oxathiazines that inhibit estrone sulfatase and have greatly reduced estrogenic side effects. Our in vitro studies indicate that the oxathiazine compounds have inhibitory activity on estrone sulfatase in MCF-7 human breast cancer cells. These estrone sulfatase inhibitors (ESIs) also inhibit the growth of MCF-7 cells induced by estrone sulfate. In addition, our in vivo experiments demonstrate that our ESIs have moderate antitumor activity against MCF-7 breast cancer xenografts in Balb/c athymic nude mice. The synthesis and biological activity of a number of these unique steroidal ESIs are described. (C) 2002 Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0039-128x(02)00118-6
• 作为产物：
  描述：

  17β-tert-butyldimethylsilyloxy-3-hydroxyestra-1,3,5(10)-trien-2-carboxaldehyde-3-acetate 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以81%的产率得到17β-tert-butyldimethylsilyloxy-3-hydroxyestra-1,3,5(10)-trien-2-carboxaldehyde
  参考文献：
  名称：

  Steroidal oxathiazine inhibitors of estrone sulfatase

  摘要：

  The presence of estrone sulfatase in breast tumors and the high levels of circulating estrone sulfate may contribute the major portion of estrogen synthesized locally in breast tissues through conversion of estrone sulfate to estrone by the enzyme. Using inhibitors of estrone sulfatase for the treatment of estrogen-dependent (estrogen receptor positive, ER+) breast cancer could be a very effective therapeutic strategy for the treatment of estrogen-dependent breast tumors in postmenopausal women. Therefore, we designed and synthesized several steroidal 2',3-oxathiazines that inhibit estrone sulfatase and have greatly reduced estrogenic side effects. Our in vitro studies indicate that the oxathiazine compounds have inhibitory activity on estrone sulfatase in MCF-7 human breast cancer cells. These estrone sulfatase inhibitors (ESIs) also inhibit the growth of MCF-7 cells induced by estrone sulfate. In addition, our in vivo experiments demonstrate that our ESIs have moderate antitumor activity against MCF-7 breast cancer xenografts in Balb/c athymic nude mice. The synthesis and biological activity of a number of these unique steroidal ESIs are described. (C) 2002 Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0039-128x(02)00118-6

文献信息

• Steriod inhibitors of estrone sulfatase and associated pharmaceutical
  申请人：SRI International

  公开号：US05763432A1

  公开（公告）日：1998-06-09

  Novel compounds useful as inhibitors of estrone sulfatase are provided. The compounds have the structural formula (I) ##STR1## wherein X and Y, or Y and Z, form an oxathiazine dioxide ring or a dihydro-oxathiazine dioxide ring, and the other various substituents are as defined herein. Pharmaceutical compositions and methods for using the compounds of formula (I) to treat estrogen-dependent disorders are provided as well.

  本发明提供了作为雌酮磺酸酶抑制剂有用的新型化合物。这些化合物具有结构式（I）##STR1## 其中X和Y或Y和Z形成一个氧硫氮环或二氢氧硫氮环，其他各种取代基如本文所定义。还提供了药物组合物和使用公式（I）化合物治疗雌激素依赖性疾病的方法。
• Steroid inhibitors of estrone sulfatase and associated pharmaceutical
  申请人：SRI International

  公开号：US05861388A1

  公开（公告）日：1999-01-19

  Novel compounds useful as inhibitors of estrone sulfatase are provided. The compounds have the structural formula (I) ##STR1## wherein X and Y, or Y and Z, form an oxathiazine dioxide ring or a dihydro-oxathiazine dioxide ring, and the other various substituents are as defined herein. Pharmaceutical compositions and methods for using the compounds of formula (I) to treat estrogen-dependent disorders are provided as well.

  本发明提供了一种作为雌酮磺酸酶抑制剂有用的新化合物。该化合物具有结构式（I）##STR1##其中X和Y，或Y和Z，形成一个噁唑二氧杂环或二氢噁唑二氧杂环，其他各种取代基的定义如本文所述。还提供了制备药物组合物和使用式（I）化合物治疗雌激素依赖性疾病的方法。