8-[3,17β-(di-tert-butyldimethylsilyloxy)-1,3,5(10)-estratrien-16β-yl]octanol | 502185-88-8

• 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: 8-[3,17β-(di-tert-butyldimethylsilyloxy)-1,3,5(10)-estratrien-16β-yl]octanol
• 英文别名: 8-[(8R,9S,13S,14S,16S,17S)-3,17-bis[[tert-butyl(dimethyl)silyl]oxy]-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-16-yl]octan-1-ol
• CAS: 502185-88-8
• 化学式: C₃₈H₆₈O₃Si₂
• 分子量: 629.127
• InChiKey: AWSQGFVVQJHZMC-FPJTZDEJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  11.27
• 重原子数：
  43
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-[3,17β-(di-tert-butyldimethylsilyloxy)-1,3,5(10)-estratrien-16β-yl]octanol 在 chromium(VI) oxide 、 草酰氯 、 硫酸 、 sodium hydride 作用下， 以 四氢呋喃 、 二氯甲烷 、 丙酮 为溶剂， 反应 3.0h， 生成 5'-O-{8-[3,17β-(di-tert-butyldimethylsilyloxy)-1,3,5(10)-estratrien-16β-yl]octanoyl} 2',3'-O-isopropylideneadenosine
  参考文献：
  名称：

  Estradiol−Adenosine Hybrid Compounds Designed to Inhibit Type 1 17β-Hydroxysteroid Dehydrogenase

  摘要：

  The steroidogenic enzyme type 1 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) is involved in the synthesis of estradiol (E-2), a hormone well-known to stimulate the growth of estrogen-sensitive tumors. To obtain compounds able to control E-2 formation, two moieties were linked with a methylene side chain: an adenosine moiety for interacting with the cofactor-binding site and an E-2 moiety for interacting with the substrate-binding site. When tested as inhibitors of type 1 17 beta-HSD, the hybrid compounds inhibited the reductive activity (E-1 into E-2) with IC50 values ranging from 52 to 1000 nM. The optimal side-chain length was determined to be eight methylene groups for a 16 beta-orientation. The presence of two components (E-2 and adenosine) is essential for good inhibition, since 16 beta-nonyl-E-2 and 5-nonanoyl-O-adenosine, two compounds having only one of the components, did not inhibit the enzyme. Moreover, the 3D-structure analysis of EM-1745 complexed with type 1 17 beta-HSD showed key interactions with both substrate- and cofactor-binding sites.

  DOI：

  10.1021/jm058235e
• 作为产物：
  描述：

  1-溴-8-(四氢吡喃氧基)辛烷 在 甲醇 、 对甲苯磺酸 作用下， 以 丙酮 为溶剂， 生成 8-[3,17β-(di-tert-butyldimethylsilyloxy)-1,3,5(10)-estratrien-16β-yl]octanol
  参考文献：
  名称：

  Estradiol−Adenosine Hybrid Compounds Designed to Inhibit Type 1 17β-Hydroxysteroid Dehydrogenase

  摘要：

  The steroidogenic enzyme type 1 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) is involved in the synthesis of estradiol (E-2), a hormone well-known to stimulate the growth of estrogen-sensitive tumors. To obtain compounds able to control E-2 formation, two moieties were linked with a methylene side chain: an adenosine moiety for interacting with the cofactor-binding site and an E-2 moiety for interacting with the substrate-binding site. When tested as inhibitors of type 1 17 beta-HSD, the hybrid compounds inhibited the reductive activity (E-1 into E-2) with IC50 values ranging from 52 to 1000 nM. The optimal side-chain length was determined to be eight methylene groups for a 16 beta-orientation. The presence of two components (E-2 and adenosine) is essential for good inhibition, since 16 beta-nonyl-E-2 and 5-nonanoyl-O-adenosine, two compounds having only one of the components, did not inhibit the enzyme. Moreover, the 3D-structure analysis of EM-1745 complexed with type 1 17 beta-HSD showed key interactions with both substrate- and cofactor-binding sites.

  DOI：

  10.1021/jm058235e