3β-hydroxy-21-(1H-1,2,4-triazole-1-yl)pregna-5,16-dien-20-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: 3β-hydroxy-21-(1H-1,2,4-triazole-1-yl)pregna-5,16-dien-20-one
• 英文别名: 3β-hydroxy-21-(1H-1,2,4-triazol-1-yl)pregna-5,16-dien-20-one；1-[(3S,8R,9S,10R,13S,14S)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,11,12,14,15-decahydro-1H-cyclopenta[a]phenanthren-17-yl]-2-(1,2,4-triazol-1-yl)ethanone
• 化学式: C₂₃H₃₁N₃O₂
• 分子量: 381.518
• InChiKey: ZMTHTANWOVKDGJ-VYAQIDIUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  68
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3β-hydroxy-21-(1H-1,2,4-triazole-1-yl)pregna-5,16-dien-20-one 、 丁酸 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 氯仿 为溶剂， 反应 2.0h， 以80%的产率得到20-oxo-21-(1H-1,2,4-triazol-1-yl)pregna-5,16-dien-3β-yl butyrate
  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
• 作为产物：
  描述：

  16α,17α-epoxy-3β-tert-butyldimethylsilyloxypregna-5-en-20-one 在 吡啶 、 chromium dichloride 、 盐酸 、 氯化亚砜 、 碘苯二乙酸 、 水 、 potassium carbonate 、 溶剂黄146 、 sodium hydroxide 作用下， 以 二氯甲烷 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 2.0h， 生成 3β-hydroxy-21-(1H-1,2,4-triazole-1-yl)pregna-5,16-dien-20-one
  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 biological activity of two pregnane derivatives with a triazole or imidazole ring at C-21
  作者：Aylin Viviana Silva-Ortiz、Eugene Bratoeff、María Teresa Ramírez-Apan、Rocío García-Becerra、David Ordaz-Rosado、Nancy Noyola-Martínez、Rafael Castillo-Bocanegra、David Barrera

  DOI：10.1016/j.jsbmb.2016.02.013

  日期：2016.5

  Pregnane derivatives are studied as agents for the treatment of different hormone-dependent diseases. The biological importance of these steroids is based on their potential use against cancer. In this study, we report the synthesis, characterization and biological activity of two pregnane derivatives with a triazole (3β-hydroxy-21-(1H-1,2,4-triazol-1-yl)pregna-5,16-dien-20-one; T–OH) or imidazole (3β-

  研究了孕烷衍生物作为治疗不同激素依赖性疾病的药物。这些类固醇的生物学重要性是基于其潜在的抗癌作用。在这项研究中，我们报告了两个三唑（3β-羟基-21-（1 H -1,2,4-三唑-1-基）pregna-5,16-dien的两个孕烷衍生物的合成，表征和生物学活性。-20-1; T–OH）或咪唑（3β-羟基-21-（1 H-咪唑-1-基）pregna-5,16-dien-20-one; I–OH）的C-21部分。这些衍生物是由乙酸16-脱氢孕烯醇酮合成的。在三种人类癌细胞系（前列腺癌（PC-3），乳腺癌（MCF7）和肺癌（SK-LU-1））上测量了化合物对细胞增殖的活性。使用SBR和XTT方法分别评估了T-OH和I-OH的细胞毒性和抗增殖作用。通过实时PCR评估基因表达。此外，结果还通过对接研究和使用表达载体孕酮和雄激素受体的反式激活法进行了补充。 结果表明，这两种化合物以剂量依赖的方式抑制了
• 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.