16β-[12-(tetrahydropyranyloxy)dodecyl]-3,17β-(di-tert-butyldimethylsilyloxy)-1,3,5(10)-estratriene | 871903-52-5

• 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: 16β-[12-(tetrahydropyranyloxy)dodecyl]-3,17β-(di-tert-butyldimethylsilyloxy)-1,3,5(10)-estratriene
• 英文别名: tert-butyl-[[(8R,9S,13S,14S,16S,17S)-3-[tert-butyl(dimethyl)silyl]oxy-13-methyl-16-[12-(oxan-2-yloxy)dodecyl]-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl]oxy]-dimethylsilane
• CAS: 871903-52-5
• 化学式: C₄₇H₈₄O₄Si₂
• 分子量: 769.353
• InChiKey: BEPVOJBOBWSVON-GDYJCTAWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  14.38
• 重原子数：
  53
• 可旋转键数：
  20
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  36.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  16β-[12-(tetrahydropyranyloxy)dodecyl]-3,17β-(di-tert-butyldimethylsilyloxy)-1,3,5(10)-estratriene 在 chromium(VI) oxide 、 甲醇 、 草酰氯 、 硫酸 、 sodium hydride 、 对甲苯磺酸 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-{12-[3,17β-(di-tert-butyldimethylsilyloxy)-1,3,5(10)-estratrien-16β-yl]dodecanoyl} 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：

  叔丁基二甲硅基三氟甲磺酸酯 、 3-(O-tert-butyl(dimethyl)silyl)estrone 、 2-[(12-bromododecyl)oxy]tetrahydro-2H-pyran 生成 16β-[12-(tetrahydropyranyloxy)dodecyl]-3,17β-(di-tert-butyldimethylsilyloxy)-1,3,5(10)-estratriene 、 tert-butyl-[[(8R,9S,13S,14S,17S)-3-[tert-butyl(dimethyl)silyl]oxy-13-methyl-16,16-bis[12-(oxan-2-yloxy)dodecyl]-7,8,9,11,12,14,15,17-octahydro-6H-cyclopenta[a]phenanthren-17-yl]oxy]-dimethylsilane
  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

文献信息

• Estradiol−Adenosine Hybrid Compounds Designed to Inhibit Type 1 17β-Hydroxysteroid Dehydrogenase
  作者：Donald Poirier、Roch P. Boivin、Martin R. Tremblay、Marie Bérubé,、Wei Qiu、Sheng-Xiang Lin

  DOI：10.1021/jm058235e

  日期：2005.12.1

  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.