7α-(E)-4-chlorobut-2-enyl-4-androsten-17β-ol-3-one acetate | 1470000-35-1

• 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: 7α-(E)-4-chlorobut-2-enyl-4-androsten-17β-ol-3-one acetate
• 英文别名: 7α-(4-chlorobut-2-enyl)-4-androsten-17β-ol-3-one acetate；7α-(4-chlorobut-2-enyl)testosterone
• CAS: 1470000-35-1
• 化学式: C₂₅H₃₅ClO₃
• 分子量: 419.004
• InChiKey: UPOBBJLOHYUNEN-NODWPGHHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.86
• 重原子数：
  29.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  43.37
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  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 为溶剂， 反应 2.0h， 以94%的产率得到7α-(4-chlorobut-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
• 作为产物：
  描述：

  7α-allyl-3-oxoandrost-4-en-17β-yl acetate 、 3-氯丙烯 在 Hoveyda-Grubbs catalyst second generation 作用下， 以 二氯甲烷 为溶剂， 反应 9.0h， 以90%的产率得到7α-(E)-4-chlorobut-2-enyl-4-androsten-17β-ol-3-one acetate
  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

• New platinum(II) complexes conjugated at position 7α of 17β-acetyl-testosterone as new combi-molecules against prostate cancer: Design, synthesis, structure–activity relationships and biological evaluation
  作者：Sébastien Fortin、Kevin Brasseur、Nathalie Morin、Éric Asselin、Gervais Bérubé

  DOI：10.1016/j.ejmech.2013.08.011

  日期：2013.10

  Prostate cancer is a major public health problem worldwide and, more specifically, new treatments for hormone-refractory cancers are highly sought by several research groups. Although platinum(II)-based chemotherapy and other strategies grow in interest to treat castration-resistant prostate cancer (CRPC), they still exhibit modest activity on CRPC and overall patient survival. In this study, we designed and prepared new combi-molecules using 17 beta-acetyl-testosterone and amino acid platinum(II) complexes linked at the position 7 alpha to target and to improve the antiproliferative activity of platinum(II)based chemotherapy on prostate cancer cells. Twelve chemical intermediates and six new combi-molecules were prepared and characterized. Structure activity relationships studies show that the platinum complex moiety is essential for an optimal cytocidal activity. Moreover, stereochemistry of the amino acid involved in the platinum complexes had only minor effects on the antiproliferative activity whereas pyridinyl (10a and b) and thiazolyl (10f) complexes exhibited the highest cytocidal activities that are significantly superior to that of cisplatin used as control on human prostate adenocarcinoma LNCaP (AR(+)), PD (AR(-)) and DU145 (AR(-)). Compounds 10a, b and f arrested the cell cycle progression in S-phase and induced double strand breaks as confirmed by the phosphorylation of histone H2AX into gamma H2AX. Compounds 10a and f showed 33 and 30% inhibition, respectively of the growth of HT-1080 tumors grafted onto chick chorioallantoic membranes. Finally, compounds 10a and 10f exhibited low toxicity on the chick embryos (18 and 21% of death, respectively), indicating that these new combi-molecules might be a promising new class of anticancer agents for prostate cancer. (C) 2013 Elsevier Masson SAS. All rights reserved.