1-[(8R,9S,13S,14S,16R,17S)-3,17-Bis-(tert-butyl-dimethyl-silanyloxy)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-16-yl]-oct-4-yn-3-ol | 184888-09-3

• 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: 1-[(8R,9S,13S,14S,16R,17S)-3,17-Bis-(tert-butyl-dimethyl-silanyloxy)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-16-yl]-oct-4-yn-3-ol
• CAS: 184888-09-3
• 化学式: C₃₈H₆₄O₃Si₂
• 分子量: 625.095
• InChiKey: HWAOQXFONWMYCZ-GVUAJHQISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.49
• 重原子数：
  43.0
• 可旋转键数：
  8.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  38.69
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  1-[(8R,9S,13S,14S,16R,17S)-3,17-Bis-(tert-butyl-dimethyl-silanyloxy)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-16-yl]-oct-4-yn-3-ol 在 盐酸 、 三溴化硼 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 2.25h， 生成 8-(3',17'β-dihydroxy-1',3',5'(10')-estratrien-16'α-yl)-6-bromo-4-octyne
  参考文献：
  名称：

  Synthesis and evaluation of estradiol derivatives with 16α-(bromoalkylamide), 16α-(bromoalkyl) or 16α-(bromoalkynyl) side chain as inhibitors of 17β-hydroxysteroid dehydrogenase type 1 without estrogenic activity

  摘要：

  To develop inhibitors of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) without residual estrogenic activity, the synthesis of 16 alpha-(bromoalkylamide) derivatives of estradiol was performed starting from a key intermediate aldehyde obtained from commercially available estrone. In addition, series of 16 alpha-(bromoalkyl) and 16 alpha-(bromoalkynyl) derivatives of estradiol were also prepared as model compounds. All new compounds inhibited human placental cytosolic 17 beta-HSD (type 1) with IC50 values ranging from 1.7 to 10.6 mu M. From these results, we observed that a primary bromide produces a greater inhibition of 17 beta-HSD activity than secondary bromide, and that a shorter 16 alpha-side chain increases the inhibiting activity. In the estrogen-sensitive ZR-75-1 human breast cancer cell line, the 16 alpha-(bromoalkylamide)-estradiol series had no estrogenic activity at 30 nM, and only the compound with a shorter side chain length showed an estrogenic activity at 1000 nM. Interestingly, at this concentration, the compound with an intermediate side chain length showed an antiestrogenic activity of 74%, whereas the compound with the longer side chain length showed 34% of antiestrogenic activity. In this test, other 17 beta-HSD inhibitors (without bromoalkylamide side chain) were fully estrogenic. Among synthesized compounds, the estradiol derivative 4 (N-butyl, N-methyl, 9-[3',17'beta-(dihydroxy)-1',3',5'(10')-estratrien-16'alpha-yl]-7-bromononamide) was the best compromise for a dual-action inhibitor. This compound inhibited moderately and reversibly the 17 beta-HSD type 1 activity, but possessed no estrogenic activity and exhibited antiestrogenic activity in the ZR-75-1 cell line. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0968-0896(96)00154-x
• 作为产物：
  描述：

  1-戊炔 、 3-<3',17'β-di-(tert-butyldimethylsilyloxy)-1',3',5'(10')-estratrien-16α-yl>propanal 在 正丁基锂 作用下， 生成 1-[(8R,9S,13S,14S,16R,17S)-3,17-Bis-(tert-butyl-dimethyl-silanyloxy)-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-16-yl]-oct-4-yn-3-ol
  参考文献：
  名称：

  Synthesis and evaluation of estradiol derivatives with 16α-(bromoalkylamide), 16α-(bromoalkyl) or 16α-(bromoalkynyl) side chain as inhibitors of 17β-hydroxysteroid dehydrogenase type 1 without estrogenic activity

  摘要：

  To develop inhibitors of 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) without residual estrogenic activity, the synthesis of 16 alpha-(bromoalkylamide) derivatives of estradiol was performed starting from a key intermediate aldehyde obtained from commercially available estrone. In addition, series of 16 alpha-(bromoalkyl) and 16 alpha-(bromoalkynyl) derivatives of estradiol were also prepared as model compounds. All new compounds inhibited human placental cytosolic 17 beta-HSD (type 1) with IC50 values ranging from 1.7 to 10.6 mu M. From these results, we observed that a primary bromide produces a greater inhibition of 17 beta-HSD activity than secondary bromide, and that a shorter 16 alpha-side chain increases the inhibiting activity. In the estrogen-sensitive ZR-75-1 human breast cancer cell line, the 16 alpha-(bromoalkylamide)-estradiol series had no estrogenic activity at 30 nM, and only the compound with a shorter side chain length showed an estrogenic activity at 1000 nM. Interestingly, at this concentration, the compound with an intermediate side chain length showed an antiestrogenic activity of 74%, whereas the compound with the longer side chain length showed 34% of antiestrogenic activity. In this test, other 17 beta-HSD inhibitors (without bromoalkylamide side chain) were fully estrogenic. Among synthesized compounds, the estradiol derivative 4 (N-butyl, N-methyl, 9-[3',17'beta-(dihydroxy)-1',3',5'(10')-estratrien-16'alpha-yl]-7-bromononamide) was the best compromise for a dual-action inhibitor. This compound inhibited moderately and reversibly the 17 beta-HSD type 1 activity, but possessed no estrogenic activity and exhibited antiestrogenic activity in the ZR-75-1 cell line. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0968-0896(96)00154-x