6α,7α-epoxypregn-4-en-3,20-dione | 3754-64-1

• 分子结构分类: 有机化合物
• 英文名称: 6α,7α-epoxypregn-4-en-3,20-dione
• 英文别名: 6α,7α-epoxypregna-4-ene-3,20-dione；6α,7α-Epoxy-pregnen-(4)-dion-(3,20)；6α,7α-epoxy-pregn-4-ene-3,20-dione；6α,7α-Epoxy-pregn-4-en-3,20-dion；(1S,2S,4R,10R,11S,14S,15S,18S)-15-acetyl-10,14-dimethyl-3-oxapentacyclo[9.7.0.02,4.05,10.014,18]octadec-5-en-7-one
• CAS: 3754-64-1
• 化学式: C₂₁H₂₈O₃
• 分子量: 328.452
• InChiKey: NKLRJTMOFLSGSA-UACKUTFGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  46.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6α,7α-epoxypregn-4-en-3,20-dione 在 吡啶 、 palladium 10% on activated carbon 、 氢气 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 30.0 ℃ 、101.33 kPa 条件下， 反应 24.0h， 以95%的产率得到7α-hydroxy-5β-pregnane-3,20-dione
  参考文献：
  名称：

  Synthesis of New Steroidal Inhibitors of P-Glycoprotein-Mediated Multidrug Resistance and Biological Evaluation on K562/R7 Erythroleukemia Cells

  摘要：

  A simple route for improving the potency of progesterone as a modulator of P-gp-mediated multidrug resistance was established by esterification or etherification of hydroxylated 5 alpha/beta-pregnane-3,20-dione or 5 beta-cholan-3-one precursors. X-ray crystallography of representative 7 alpha-, 11 alpha-, and 17 alpha-(2'R/S)-O-tetrahydropyranyl ether diastereoisomers revealed different combinations of axial-equatorial configurations of the anomeric oxygen. Substantial stimulation of accumulation and chemosensitization was observed on K562/R7 erythroleukemia cells resistant to doxorubicin, especially using 7 alpha,11 alpha-O-disubstituted derivatives of 5 alpha/beta-pregnane-3,20-dione, among which the 5 beta-H-7 alpha-benzoyloxy-11 alpha-(2'R)-O-tetrahydropyranyl ether 22a revealed promising properties (accumulation index 2.9, IC50 0.5 mu M versus 1.2 and 10.6 mu M for progesterone), slightly overcoming those of verapamil and cyclosporin A. Several 7 alpha,12 alpha-O-disubstituted derivatives of 5 beta-cholan-3-one proved even more active, especially the 7 alpha-O-methoxymethyl-12 alpha-benzoate 56 (accumulation index 3.8, IC50 0.2 mu M). The panel of modulating effects from different O-substitutions at a same position suggests a structural influence of the substituent completing a simple protection against stimulating effects of hydroxyl groups on P-gp-mediated transport.

  DOI：

  10.1021/jm501676v
• 作为产物：
  描述：

  6-去氢黄体酮 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以37%的产率得到6α,7α-epoxypregn-4-en-3,20-dione
  参考文献：
  名称：

  Synthesis of New Steroidal Inhibitors of P-Glycoprotein-Mediated Multidrug Resistance and Biological Evaluation on K562/R7 Erythroleukemia Cells

  摘要：

  A simple route for improving the potency of progesterone as a modulator of P-gp-mediated multidrug resistance was established by esterification or etherification of hydroxylated 5 alpha/beta-pregnane-3,20-dione or 5 beta-cholan-3-one precursors. X-ray crystallography of representative 7 alpha-, 11 alpha-, and 17 alpha-(2'R/S)-O-tetrahydropyranyl ether diastereoisomers revealed different combinations of axial-equatorial configurations of the anomeric oxygen. Substantial stimulation of accumulation and chemosensitization was observed on K562/R7 erythroleukemia cells resistant to doxorubicin, especially using 7 alpha,11 alpha-O-disubstituted derivatives of 5 alpha/beta-pregnane-3,20-dione, among which the 5 beta-H-7 alpha-benzoyloxy-11 alpha-(2'R)-O-tetrahydropyranyl ether 22a revealed promising properties (accumulation index 2.9, IC50 0.5 mu M versus 1.2 and 10.6 mu M for progesterone), slightly overcoming those of verapamil and cyclosporin A. Several 7 alpha,12 alpha-O-disubstituted derivatives of 5 beta-cholan-3-one proved even more active, especially the 7 alpha-O-methoxymethyl-12 alpha-benzoate 56 (accumulation index 3.8, IC50 0.2 mu M). The panel of modulating effects from different O-substitutions at a same position suggests a structural influence of the substituent completing a simple protection against stimulating effects of hydroxyl groups on P-gp-mediated transport.

  DOI：

  10.1021/jm501676v

文献信息

• Bile Acids and Steroids. XXVIII. Thiosteroids. (13). Further Study on Synthesis of 5'-Methylthieno-[4', 3', 2'-4, 5, 6]-5-en-3-one Steroids
  作者：Ken'ichi Takeda、Taichiro Komeno、Shoichi Ishihara

  DOI：10.1248/cpb.12.1433

  日期：——

  By treatment of potassium thiolacetate 6β-bromo-4-en-3-one steroids were converted to 6α-acetylthio-4-en-3-ones, which were further converted to 5'-methylthieno [4', 3', 2'-4, 5, 6]-5-en-3-ones by heating with sodium hydride in toluene

  经硫代乙酸钾处理后，6β-溴-4-烯-3-酮类固醇转化为 6α-乙酰硫基-4-烯-3-酮，在甲苯中用氢化钠加热，进一步转化为 5'-甲基噻吩基 [4'，3'，2'-4，5，6]-5-烯-3-酮
• 6,7-epoxy-3-ketosteroids
  申请人：SEARLE &

  公开号：US02738348A1

  公开（公告）日：1956-03-13