5'-O-{12-[3,17β-(di-tert-butyldimethylsilyloxy)-1,3,5(10)-estratrien-16β-yl]dodecanoyl} 2',3'-O-isopropylideneadenosine | 871903-74-1

• 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: 5'-O-{12-[3,17β-(di-tert-butyldimethylsilyloxy)-1,3,5(10)-estratrien-16β-yl]dodecanoyl} 2',3'-O-isopropylideneadenosine
• 英文别名: [(3aR,4R,6R,6aR)-4-(6-aminopurin-9-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methyl 12-[(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]dodecanoate
• CAS: 871903-74-1
• 化学式: C₅₅H₈₉N₅O₇Si₂
• 分子量: 988.512
• InChiKey: SUEDDMMXFYTRRV-KAPHNCRYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  13.22
• 重原子数：
  69
• 可旋转键数：
  22
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  142
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  5'-O-{12-[3,17β-(di-tert-butyldimethylsilyloxy)-1,3,5(10)-estratrien-16β-yl]dodecanoyl} 2',3'-O-isopropylideneadenosine 在 盐酸 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 5'-O-{12-[3,17β-dihydroxy-1,3,5(10)-estratrien-16β-yl]dodecanoyl} adenosine
  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：

  2-[(12-bromododecyl)oxy]tetrahydro-2H-pyran 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

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.