3β-acetoxy-17-methanesulfonyloxy-16,17-seco-androst-5-ene-16-nitrile | 1252022-88-0

• 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: 3β-acetoxy-17-methanesulfonyloxy-16,17-seco-androst-5-ene-16-nitrile
• CAS: 1252022-88-0
• 化学式: C₂₂H₃₃NO₅S
• 分子量: 423.574
• InChiKey: BXBPGLIICORDRU-LLTZGFESSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.98
• 重原子数：
  29.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  93.46
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  3β-acetoxy-17-methanesulfonyloxy-16,17-seco-androst-5-ene-16-nitrile 在 sodium ethanolate 作用下， 以 乙醇 、 二甲基亚砜 为溶剂， 反应 8.5h， 生成 3β-hydroxy-16,17-secoandrost-5-ene-16,17a-dinitrile
  参考文献：
  名称：

  Synthesis and anticancer cell potential of steroidal 16,17-seco-16,17a-dinitriles: Identification of a selective inhibitor of hormone-independent breast cancer cells

  摘要：

  We report the synthesis of steroidal 16,17-seco-16,17a-dinitriles and investigate their antitumor cell properties. Compounds were evaluated for anticancer potential by in vitro antiproliferation studies, molecular docking and virtual screening. Several compounds inhibit the growth of breast and prostate cancer cell lines (MCF-7, MDA-MB-231 and PC3), and/or cervical cancer cells (HeLa). Supporting this, molecular docking predicts that steroidal 16,17-seco-16,17a-dinitriles could bind with high affinity to multiple molecular targets of breast and prostate cancer treatment (aromatase, estrogen receptor alpha, androgen receptor and 17 alpha-hydroxylase) facilitated by D-seco flexibility and nitrile-mediated contacts. Thus, 16,17-seco-16,17a-dinitriles may be useful for the design of inhibitors of multiple steroidogenesis pathways. Strikingly, 10, a 1,4-dien-3-on derivative, displayed selective submicromolar antiproliferative activity against hormone-dependent (MCF-7) and -independent (MDA-MB-231) breast cancer cells (IC50 0.52, 0.11 mu M, respectively). Ligand-based 3D similarity searches suggest AKR1C, 17 beta-HSD and/or 3 beta-HSD subfamilies as responsible for this antiproliferative activity, while fast molecular docking identified AKR1C and ER beta as potential binders-both targets in the treatment of hormone-independent breast cancers. (c) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.12.069
• 作为产物：
  描述：

  [(2S,4aR,4bS,7S,8S,8aR)-8-(cyanomethyl)-7-(hydroxymethyl)-4a,7-dimethyl-1,2,3,4,4b,5,6,8,8a,9-decahydrophenanthren-2-yl] acetate 、 甲基磺酰氯 在 吡啶 作用下， 以86%的产率得到3β-acetoxy-17-methanesulfonyloxy-16,17-seco-androst-5-ene-16-nitrile
  参考文献：
  名称：

  新合成的d-均质甾族四唑的选择性抗肿瘤活性和ERα分子对接研究†

  摘要：

  在这里，我们报告一个方便的“点击”合成为d -homo融合甾体四唑11-14从Androstane 和 雌三烯16,17-seco-16-腈-17-甲磺酰氧基衍生物5-8，通过分子内1,3-偶极环加成反应原位生成16,17-seco-17-azido-16-腈5a-8a。产品通过1 H / 13 C-NMR，IR，HRMS验证，并通过X射线晶体学和计算方法进行结构表征。化合物被评估为针对一组人类癌细胞系的潜在抗增殖剂。D-人稠合的甾体四唑13和14似乎对雌激素受体阳性（ER +）乳腺癌细胞具有特异性，选择性的抗增殖作用，这与分子对接至雌激素受体α-配体结合域（ERα-LBD）的结合能有关。此外，分子对接表明，D环稠合的甾体四唑13和14可以以类似于已知抗雌激素化合物的方式结合到ERα-LBD。一个的加成d -homo稠合的四唑基团出现在结构上模仿β雌二醇的氢键潜力，这表明在设计新甾族四唑衍

  DOI：

  10.1039/c2md20327h