3β-hydroxy-16,17-secoandrost-5-ene-16,17a-dinitrile | 1382358-09-9

• 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-hydroxy-16,17-secoandrost-5-ene-16,17a-dinitrile
• 英文别名: 3β-hydroxy-16,17-seco-5-androstene-16,17-dinitrile
• CAS: 1382358-09-9
• 化学式: C₁₉H₂₆N₂O
• 分子量: 298.428
• InChiKey: GIXZTJAIMSWXCA-VIUKOLAESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.95
• 重原子数：
  22.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  67.81
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  3β-hydroxy-16,17-secoandrost-5-ene-16,17a-dinitrile 在 aluminum isopropoxide 作用下， 以 环己酮 、 甲苯 为溶剂， 以50%的产率得到3-oxo-16,17-secoandrost-4-ene-16,17a-dinitrile
  参考文献：
  名称：

  Steroidal carbonitriles as potential aromatase inhibitors

  摘要：

  Estrogens, responsible for the growth of hormone-dependant breast cancer are biosynthesized from androgens involving aromatase enzyme in the last rate limiting step. Inhibition of aromatase is an efficient approach for the prevention and treatment of breast cancer. Novel 4-phenylthia derivatives (2, 3 and 7) have been synthesized as aromatase inhibitors. The synthesized compounds (2,3 and 7) exhibited noticeable enzyme inhibiting activity. Kinetics study of these compounds (2, 3, and 7) showed negligible inhibition of the enzyme under conditions conducive for irreversible inhibition of the enzyme. Introduction of unsaturation at C-4, C-1 & 4 or C-4 & 6 (compounds 5, 9 and 11) was observed to not be an effective strategy for entrancing aromatase inhibiting activity in 17-oxo-16 beta-carbonitrile derivatives. The D-seco derivatives (13-15 and 17) having unsaturation at C-4, C-1 & 4 or C-4 & 6 along with carbonitrile function in ring-D showed complete loss of aromatase inhibiting activity. (c) 2012 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2012.04.010
• 作为产物：
  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