16α-(3-iodopropyl)-3α-methoxy-5α-androstan-17β-ol

• 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: 16α-(3-iodopropyl)-3α-methoxy-5α-androstan-17β-ol
• 英文别名: (3R,5S,8R,9S,10S,13S,14S,16R,17S)-16-(3-iodopropyl)-3-methoxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-ol
• 化学式: C₂₃H₃₉IO₂
• 分子量: 474.466
• InChiKey: QHDIPJDEJUBBGW-YMKYFCOASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  雄诺龙 在 2,6-二甲基吡啶 、 盐酸 、 lithium aluminium tetrahydride 、 四丙基高钌酸铵 、 硼烷四氢呋喃络合物 、 15-冠醚-5 、 四溴化碳 、 4 A molecular sieve 、 sodium hydride 、 potassium tri-sec-butyl-borohydride 、 对甲苯磺酸 、 N-甲基吗啉氧化物 、 三苯基膦 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 、 丙酮 、 苯 为溶剂， 反应 101.5h， 生成 16α-(3-iodopropyl)-3α-methoxy-5α-androstan-17β-ol
  参考文献：
  名称：

  Chemical synthesis and biological activities of 16α-derivatives of 5α-androstane-3α,17β-diol as antiandrogens

  摘要：

  In our efforts to develop compounds with therapeutic potential as antiandrogens, we synthesized a series of 5 alpha-androstane-3 alpha,17 beta-diol derivatives with a fixed side-chain length of 3-methylenes at C-16 alpha, but bearing a diversity of functional groups at the end. Among these, the chloride induced the best antiproliferative activity on androgen-sensitive Shionogi cells. Substituting the OH at C-3 by a methoxy group showed the importance of the OH. Moreover, its transformation into a ketone increased the androgen receptor (AR) binding but decreased the anti proliferative activity and induced a proliferative effect on Shionogi cells. These results confirm the importance of keeping a 5 alpha-androstane-3 alpha, 17 beta-diol nucleus instead of a dihydrotestosterone nucleus. Variable side-chain lengths of 2-, 3-, 4-, and 6-methylenes at C-16a were investigated and the optimal length was found to be 3-methylenes. Although exhibiting a weak AR binding affinity, 16 alpha-(3'-chloropropyl)-5 alpha-androstane-3ot,17 beta-diol (15) provided an antiproliferative activity on Shionogi cells similar to that of pure non-steroidal antiandrogen hydroxy-flutamide (77% and 67%, respectively, at 0.1 mu M). The new steroidal compound, 15, thus constitutes a good starting point for development of future antiandrogens with a therapeutic potential against prostate cancer. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.02.007

文献信息

• Chemical synthesis and biological activities of 16α-derivatives of 5α-androstane-3α,17β-diol as antiandrogens
  作者：Jenny Roy、Rock Breton、Céline Martel、Fernand Labrie、Donald Poirier

  DOI：10.1016/j.bmc.2007.02.007

  日期：2007.4

  In our efforts to develop compounds with therapeutic potential as antiandrogens, we synthesized a series of 5 alpha-androstane-3 alpha,17 beta-diol derivatives with a fixed side-chain length of 3-methylenes at C-16 alpha, but bearing a diversity of functional groups at the end. Among these, the chloride induced the best antiproliferative activity on androgen-sensitive Shionogi cells. Substituting the OH at C-3 by a methoxy group showed the importance of the OH. Moreover, its transformation into a ketone increased the androgen receptor (AR) binding but decreased the anti proliferative activity and induced a proliferative effect on Shionogi cells. These results confirm the importance of keeping a 5 alpha-androstane-3 alpha, 17 beta-diol nucleus instead of a dihydrotestosterone nucleus. Variable side-chain lengths of 2-, 3-, 4-, and 6-methylenes at C-16a were investigated and the optimal length was found to be 3-methylenes. Although exhibiting a weak AR binding affinity, 16 alpha-(3'-chloropropyl)-5 alpha-androstane-3ot,17 beta-diol (15) provided an antiproliferative activity on Shionogi cells similar to that of pure non-steroidal antiandrogen hydroxy-flutamide (77% and 67%, respectively, at 0.1 mu M). The new steroidal compound, 15, thus constitutes a good starting point for development of future antiandrogens with a therapeutic potential against prostate cancer. (c) 2007 Elsevier Ltd. All rights reserved.