7β,19-dihydroxy-3,3-(ethylenedioxy)-5-androsten-17β-yl acetate | 233768-88-2

• 分子结构分类: 有机化合物
• 英文名称: 7β,19-dihydroxy-3,3-(ethylenedioxy)-5-androsten-17β-yl acetate
• 英文别名: [(7R,8R,9S,10S,13S,14S,17S)-7-hydroxy-10-(hydroxymethyl)-13-methylspiro[1,2,4,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthrene-3,2'-1,3-dioxolane]-17-yl] acetate
• CAS: 233768-88-2
• 化学式: C₂₃H₃₄O₆
• 分子量: 406.519
• InChiKey: LLWJGZOWSXHZTE-NTNVJIBLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  85.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  7β,19-dihydroxy-3,3-(ethylenedioxy)-5-androsten-17β-yl acetate 在 palladium on activated charcoal 吡啶 、 chromium(VI) oxide 、 氢氧化钾 、 sodium tetrahydroborate 、 cerium(III) chloride 、 水 、 氢气 、 三乙基硼氢化锂 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 丙酮 为溶剂， 4.0~65.0 ℃ 、101.33 kPa 条件下， 反应 130.75h， 生成 5-二氢-19-去甲睾酮
  参考文献：
  名称：

  7α-Iodo and 7α-Fluoro Steroids as Androgen Receptor-Mediated Imaging Agents

  摘要：

  We have synthesized several 7 alpha-fluoro (F) and 7 alpha-iodo (I) analogues of 5 alpha-dihydrotestosterone (5 alpha-DHT) and 19-nor-5 alpha-dihydrotestosterone (5 alpha-NDHT) and tested them for binding to the androgen receptor and for their biological activity in;an in vitro assay with cells that have been engineered to respond to androgens. The relative binding affinity to the androgen receptor determined in competition assays showed that in the androstane series the fluoro steroids have the highest affinity and that F-17 alpha-CH3-DHT (4) has a higher affinity than 5 alpha-DHT. All other steroids were somewhat less potent than 5 alpha-DHT with F-DHT (2) = I-17 alpha-CH3-DHT (3) greater than or equal to F-NDHT (6) > F-17 alpha-CH3-NDHT (8) = I-DHT (1) greater than or equal to I-NDHT (5) > I-17 alpha-CH3-NDHT (7). The relative biological activity in cells transfected with the androgen receptor and an androgen responsive reporter gene is 4 much greater than 5 alpha-DHT > 2 > 6 > 3 greater than or equal to 1 greater than or equal to 8 greater than or equal to 5 > 7. The iodinated compound, I-17 alpha-CH3-DHT (3), with the highest binding activity was synthesized labeled with I-125 and was shown to bind with high affinity, K-a = 1.9 x 10(10) L/mol, and low nonspecific binding to the androgen receptor in rat prostatic cytosol. However, when radiolabeled [I-125]-17 alpha-CH3-DHT ([I-125]3) was injected into castrated male rats, it showed very poor androgen receptor-mediated uptake into the rat prostate. This was unexpected in light of its superior receptor binding properties and its protection by the 17 alpha-methyl group from metabolic oxidation at C-17. However, the biological potency of I-17 alpha-CH3-DHT (3) was not as high as would have been expected. When I-DHT (1) and I-17 alpha-CH3-DHT (3) were incubated in aqueous media at 37 degrees C they rapidly decomposed, but they were stable at 0 degrees C. The fluorinated analogue 4 treated similarly at 37 degrees C was completely stable. The products of the decomposition reaction of I-DHT (1) at 37 degrees C were identified as iodide and principally 17 beta-hydroxy-5 alpha-androst-7-en-3-one. The temperature dependence of this elimination reaction explains the inconsistency between the high binding to the androgen receptor (measured at 0 degrees C) and the low biological activity, as well as the poor androgen receptor mediated concentration in vivo. The fluorinated analogue F-17 alpha-CH3-DHT (4) has both high affinity for the androgen receptor and high stability in aqueous media. Of the compounds tested, 4 has the highest affinity for the androgen receptor as well as the highest androgenic activity. Thus it is likely that F-17 alpha-CH3-DHT 4 labeled with F-18 will be an excellent receptor-mediated diagnostic imaging agent.

  DOI：

  10.1021/jm990064o
• 作为产物：
  描述：

  19-(tert-butyldiphenylsiloxy)-3,3-(ethylenedioxy)-7β-hydroxyandrost-5-en-17β-yl acetate 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以81%的产率得到7β,19-dihydroxy-3,3-(ethylenedioxy)-5-androsten-17β-yl acetate
  参考文献：
  名称：

  7α-Iodo and 7α-Fluoro Steroids as Androgen Receptor-Mediated Imaging Agents

  摘要：

  We have synthesized several 7 alpha-fluoro (F) and 7 alpha-iodo (I) analogues of 5 alpha-dihydrotestosterone (5 alpha-DHT) and 19-nor-5 alpha-dihydrotestosterone (5 alpha-NDHT) and tested them for binding to the androgen receptor and for their biological activity in;an in vitro assay with cells that have been engineered to respond to androgens. The relative binding affinity to the androgen receptor determined in competition assays showed that in the androstane series the fluoro steroids have the highest affinity and that F-17 alpha-CH3-DHT (4) has a higher affinity than 5 alpha-DHT. All other steroids were somewhat less potent than 5 alpha-DHT with F-DHT (2) = I-17 alpha-CH3-DHT (3) greater than or equal to F-NDHT (6) > F-17 alpha-CH3-NDHT (8) = I-DHT (1) greater than or equal to I-NDHT (5) > I-17 alpha-CH3-NDHT (7). The relative biological activity in cells transfected with the androgen receptor and an androgen responsive reporter gene is 4 much greater than 5 alpha-DHT > 2 > 6 > 3 greater than or equal to 1 greater than or equal to 8 greater than or equal to 5 > 7. The iodinated compound, I-17 alpha-CH3-DHT (3), with the highest binding activity was synthesized labeled with I-125 and was shown to bind with high affinity, K-a = 1.9 x 10(10) L/mol, and low nonspecific binding to the androgen receptor in rat prostatic cytosol. However, when radiolabeled [I-125]-17 alpha-CH3-DHT ([I-125]3) was injected into castrated male rats, it showed very poor androgen receptor-mediated uptake into the rat prostate. This was unexpected in light of its superior receptor binding properties and its protection by the 17 alpha-methyl group from metabolic oxidation at C-17. However, the biological potency of I-17 alpha-CH3-DHT (3) was not as high as would have been expected. When I-DHT (1) and I-17 alpha-CH3-DHT (3) were incubated in aqueous media at 37 degrees C they rapidly decomposed, but they were stable at 0 degrees C. The fluorinated analogue 4 treated similarly at 37 degrees C was completely stable. The products of the decomposition reaction of I-DHT (1) at 37 degrees C were identified as iodide and principally 17 beta-hydroxy-5 alpha-androst-7-en-3-one. The temperature dependence of this elimination reaction explains the inconsistency between the high binding to the androgen receptor (measured at 0 degrees C) and the low biological activity, as well as the poor androgen receptor mediated concentration in vivo. The fluorinated analogue F-17 alpha-CH3-DHT (4) has both high affinity for the androgen receptor and high stability in aqueous media. Of the compounds tested, 4 has the highest affinity for the androgen receptor as well as the highest androgenic activity. Thus it is likely that F-17 alpha-CH3-DHT 4 labeled with F-18 will be an excellent receptor-mediated diagnostic imaging agent.

  DOI：

  10.1021/jm990064o