20-oxo-21-(1H-1,2,4-triazol-1-yl)pregna-5,16-dien-3β-yl propionate

• 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: 20-oxo-21-(1H-1,2,4-triazol-1-yl)pregna-5,16-dien-3β-yl propionate
• 英文别名: [(3S,8R,9S,10R,13S,14S)-10,13-dimethyl-17-[2-(1,2,4-triazol-1-yl)acetyl]-2,3,4,7,8,9,11,12,14,15-decahydro-1H-cyclopenta[a]phenanthren-3-yl] propanoate
• 化学式: C₂₆H₃₅N₃O₃
• 分子量: 437.582
• InChiKey: LJHTZCMILIAALY-PAASFTFBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  74.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  16α,17α-epoxy-3β-tert-butyldimethylsilyloxypregna-5-en-20-one 在 吡啶 、 chromium dichloride 、 盐酸 、 4-二甲氨基吡啶 、 氯化亚砜 、 碘苯二乙酸 、 水 、 potassium carbonate 、 溶剂黄146 、 N,N'-二环己基碳二亚胺 、 sodium hydroxide 作用下， 以 二氯甲烷 、 氯仿 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 4.0h， 生成 20-oxo-21-(1H-1,2,4-triazol-1-yl)pregna-5,16-dien-3β-yl propionate
  参考文献：
  名称：

  Synthesis and activity of novel 16-dehydropregnenolone acetate derivatives as inhibitors of type 1 5α-reductase and on cancer cell line SK-LU-1

  摘要：

  Testosterone (T) plays a crucial role in prostate growth. In androgen-dependent tissues T is reduced to dihydrotestosterone (DHT) because of the presence of the 5 alpha-reductase enzyme. This androgen is more active than T, since it has a higher affinity for the androgen receptor (AR). When this mechanism is altered, androgen-dependent diseases, including prostate cancer, could result.The aim of this study was to synthesize several 16-dehydropregnenolone acetate derivatives containing a triazole ring at C-21 and a linear or alicyclic ester moiety at C-3 of the steroidal skeleton. These steroids were designed as potential inhibitors of the activity of both types (1 and 2) of 5 alpha-reductase. The cytotoxic activity of these compounds was also evaluated on a panel of PC-3, MCF7, and SK-LU-1 human cancer cell lines.The results from this study showed that with the exception of steroids 20-oxo-21-(1H-1,2,4-triazole-1-yl) pregna-5,16-dien-3 beta-yl-propionate and 20-oxo-21-(1H-1,2,4-triazole-1-yl) pregna-5,16-dien-3 beta-yl-pentanoate, the compounds exhibit a lower inhibitory activity for both isoenzymes of 5 alpha-reductase than finasteride. Furthermore the 3 beta-hydroxy-21-(1H-1,2,4-triazole-1-yl) pregna-5,16-dien-20-one and 20-oxo-21-(1H-1,2,4-triazole-1-yl) pregna-5,16-dien-3 beta-yl-acetate derivatives display 80% cytotoxic activity on the SK-LU-1 cell line.These results also indicated that the triazole derivatives, which have a hydroxyl or acetoxy group at C3, could have an anticancer effect, whereas the derivatives with a alicyclic ester group at C-3 do not show biological activity. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.10.047

文献信息

• Synthesis and activity of novel 16-dehydropregnenolone acetate derivatives as inhibitors of type 1 5α-reductase and on cancer cell line SK-LU-1
  作者：Aylin Viviana Silva-Ortiz、Eugene Bratoeff、Teresa Ramírez-Apan、Yvonne Heuze、Araceli Sánchez、Juan Soriano、Marisa Cabeza

  DOI：10.1016/j.bmc.2015.10.047

  日期：2015.12

  Testosterone (T) plays a crucial role in prostate growth. In androgen-dependent tissues T is reduced to dihydrotestosterone (DHT) because of the presence of the 5 alpha-reductase enzyme. This androgen is more active than T, since it has a higher affinity for the androgen receptor (AR). When this mechanism is altered, androgen-dependent diseases, including prostate cancer, could result.The aim of this study was to synthesize several 16-dehydropregnenolone acetate derivatives containing a triazole ring at C-21 and a linear or alicyclic ester moiety at C-3 of the steroidal skeleton. These steroids were designed as potential inhibitors of the activity of both types (1 and 2) of 5 alpha-reductase. The cytotoxic activity of these compounds was also evaluated on a panel of PC-3, MCF7, and SK-LU-1 human cancer cell lines.The results from this study showed that with the exception of steroids 20-oxo-21-(1H-1,2,4-triazole-1-yl) pregna-5,16-dien-3 beta-yl-propionate and 20-oxo-21-(1H-1,2,4-triazole-1-yl) pregna-5,16-dien-3 beta-yl-pentanoate, the compounds exhibit a lower inhibitory activity for both isoenzymes of 5 alpha-reductase than finasteride. Furthermore the 3 beta-hydroxy-21-(1H-1,2,4-triazole-1-yl) pregna-5,16-dien-20-one and 20-oxo-21-(1H-1,2,4-triazole-1-yl) pregna-5,16-dien-3 beta-yl-acetate derivatives display 80% cytotoxic activity on the SK-LU-1 cell line.These results also indicated that the triazole derivatives, which have a hydroxyl or acetoxy group at C3, could have an anticancer effect, whereas the derivatives with a alicyclic ester group at C-3 do not show biological activity. (C) 2015 Elsevier Ltd. All rights reserved.