7α-(4-(4-(bis(2-chloroethyl)amino)phenylpropylcarbonyloxy)but-2-enyl)-4-androsten-17β-ol-3-one

• 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: 7α-(4-(4-(bis(2-chloroethyl)amino)phenylpropylcarbonyloxy)but-2-enyl)-4-androsten-17β-ol-3-one
• 英文别名: [(E)-4-[(7R,8R,9S,10R,13S,14S,17S)-17-hydroxy-10,13-dimethyl-3-oxo-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-7-yl]but-2-enyl] 4-[4-[bis(2-chloroethyl)amino]phenyl]butanoate
• 化学式: C₃₇H₅₁Cl₂NO₄
• 分子量: 644.722
• InChiKey: WHEHTTVEXULZJE-XXOTXUDSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  44
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  7α-(E)-4-chlorobut-2-enyl-4-androsten-17β-ol-3-one acetate 在 盐酸 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.0h， 生成 7α-(4-(4-(bis(2-chloroethyl)amino)phenylpropylcarbonyloxy)but-2-enyl)-4-androsten-17β-ol-3-one 、 7α-(4-(4-(bis(2-chloroethyl)amino)phenylpropylcarbonyloxy)but-2-enyl)-4-androsten-17β-ol-3-one
  参考文献：
  名称：

  Synthesis and preliminary in vitro biological evaluation of 7α-testosterone–chlorambucil hybrid designed for the treatment of prostate cancer

  摘要：

  The synthesis of 7 alpha-testosterone-chlorambucil hybrid is reported. This compound is made from testosterone in a 6 step reaction sequence and with 23% overall yield. An alternative convergent reaction sequence yielded the same hybrid through a Grubbs metathesis reaction between chlorambucil allyl ester and 7 alpha-allyltestosterone with 35% overall yield. KIT assays showed that the hybrid is selective towards hormone-dependent prostate cancer cell line (LNCaP (AR+)) and shows similar activity than the parent drug, chlorambucil. Thus, the new hybrid shows promising potential for drug targeting of hormone-dependent prostate cancer through its capacity of delivering chlorambucil directly to the site of treatment. This could extend the use of chlorambucil to prostate cancer in the future. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.04.027

文献信息

• Synthesis and preliminary in vitro biological evaluation of 7α-testosterone–chlorambucil hybrid designed for the treatment of prostate cancer
  作者：Dominic Bastien、Rana Hanna、Valérie Leblanc、Éric Asselin、Gervais Bérubé

  DOI：10.1016/j.ejmech.2013.04.027

  日期：2013.6

  The synthesis of 7 alpha-testosterone-chlorambucil hybrid is reported. This compound is made from testosterone in a 6 step reaction sequence and with 23% overall yield. An alternative convergent reaction sequence yielded the same hybrid through a Grubbs metathesis reaction between chlorambucil allyl ester and 7 alpha-allyltestosterone with 35% overall yield. KIT assays showed that the hybrid is selective towards hormone-dependent prostate cancer cell line (LNCaP (AR+)) and shows similar activity than the parent drug, chlorambucil. Thus, the new hybrid shows promising potential for drug targeting of hormone-dependent prostate cancer through its capacity of delivering chlorambucil directly to the site of treatment. This could extend the use of chlorambucil to prostate cancer in the future. (C) 2013 Elsevier Masson SAS. All rights reserved.