11β-hydroxy-3-methoxyestra-1,3,5(10)-trien-17β-ol | 14292-07-0

• 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: 11β-hydroxy-3-methoxyestra-1,3,5(10)-trien-17β-ol
• 英文别名: 3-methoxy-11β,17β-dihydroxy-estra-1,3,5(10)-triene；11beta,17beta-Dihydroxy-3-methoxy-estra-1,3,5(10)-triene；(8S,9S,11S,13S,14S,17S)-3-methoxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-11,17-diol
• CAS: 14292-07-0
• 化学式: C₁₉H₂₆O₃
• 分子量: 302.414
• InChiKey: QWOHYQRSCIQCKW-VIUKOLAESA-N

物化性质

• 熔点：
  153-154 °C
• 沸点：
  472.6±45.0 °C(Predicted)
• 密度：
  1.185±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  49.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  11β-hydroxy-3-methoxyestra-1,3,5(10)-trien-17β-ol 在 盐酸 、 氨 、 lithium 作用下， 生成 11β,17β-dihydroxy-4-estren-3-one
  参考文献：
  名称：

  Synthesis of 11.beta.-[18F]Fluoro-5.alpha.-dihydrotestosterone and 11.beta.-[18F]Fluoro-19-nor-5.alpha.-dihydrotestosterone: Preparation via Halofluorination-Reduction, Receptor Binding, and Tissue Distribution

  摘要：

  We have prepared 11 beta-fluoro-5 alpha-dihydrotestosterone (11 beta-F-DHT, 1) and 11 beta-fluoro-19-nor-5 alpha-dihydrotestosterone (11 beta-F-19-nor-DHT, 2) in order to investigate the properties of these new androgens labeled with fluorine-18 as potential androgen receptor (AR)-based imaging agents for prostate cancer. These compounds were synthesized in 6 steps from hydrocortisone and in 13 steps from 1,4-androstadiene-3,11,17-trione, respectively. Relative binding affinities (RBA) of 11 beta-F-DHT and 11 beta-F-19-nor-DHT to AR are 53.1 and 75.3 (R1881 = 100), respectively, the latter being the highest reported among fluorine-substituted androgens. The fluorination step, which involves addition of halogen fluoride across the 9(11)-double bond, followed by reductive dehalogenation at the 9 alpha-position has been adapted to introduce a fluorine-18-label at the 11 beta-position of DHT and 19-nor-DHT. The two high-affinity F-18-labeled ligands [F-18]-1 and [F-18]-2 were evaluated in vivo, in tissue distribution studies using diethylstilbestrol-pretreated mature male rats. 11 beta-F-DHT shows high prostate uptake and selective prostate to blood and prostate to muscle uptake ratios, the latter two ratios increasing from 5 and 8 at 1 h to 12 and 19 at 4 h postinjection. Moreover, this compound has low uptake in bone, displaying the lowest in vivo defluorination among all androgens labeled with fluorine-18 tested so far. The in vive properties of 11 beta-F-DHT in rats are thus favorable for imaging of prostate cancer. On the other hand, 11 beta-F-19-nor-DHT shows low prostate uptake with low selectivity and high uptake in liver, kidney, and bladder. Even though this ligand has the highest RBA and undergoes little metabolic defluorination, it appears to suffer from rapid metabolism in vivo. Therefore, it is apparent that the biodistribution properties of androgens are affected by their structure and metabolism as well as by their RBA.

  DOI：

  10.1021/jm00005a009
• 作为产物：
  描述：

  (8'S,9'S,11'S,13'S,14'S)-3'-methoxy-13'-methylspiro[1,3-dioxolane-2,17'-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene]-11'-ol 在 盐酸 、 sodium tetrahydroborate 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 3.0h， 生成 11β-hydroxy-3-methoxyestra-1,3,5(10)-trien-17β-ol
  参考文献：
  名称：

  Synthesis of 11.beta.-[18F]Fluoro-5.alpha.-dihydrotestosterone and 11.beta.-[18F]Fluoro-19-nor-5.alpha.-dihydrotestosterone: Preparation via Halofluorination-Reduction, Receptor Binding, and Tissue Distribution

  摘要：

  We have prepared 11 beta-fluoro-5 alpha-dihydrotestosterone (11 beta-F-DHT, 1) and 11 beta-fluoro-19-nor-5 alpha-dihydrotestosterone (11 beta-F-19-nor-DHT, 2) in order to investigate the properties of these new androgens labeled with fluorine-18 as potential androgen receptor (AR)-based imaging agents for prostate cancer. These compounds were synthesized in 6 steps from hydrocortisone and in 13 steps from 1,4-androstadiene-3,11,17-trione, respectively. Relative binding affinities (RBA) of 11 beta-F-DHT and 11 beta-F-19-nor-DHT to AR are 53.1 and 75.3 (R1881 = 100), respectively, the latter being the highest reported among fluorine-substituted androgens. The fluorination step, which involves addition of halogen fluoride across the 9(11)-double bond, followed by reductive dehalogenation at the 9 alpha-position has been adapted to introduce a fluorine-18-label at the 11 beta-position of DHT and 19-nor-DHT. The two high-affinity F-18-labeled ligands [F-18]-1 and [F-18]-2 were evaluated in vivo, in tissue distribution studies using diethylstilbestrol-pretreated mature male rats. 11 beta-F-DHT shows high prostate uptake and selective prostate to blood and prostate to muscle uptake ratios, the latter two ratios increasing from 5 and 8 at 1 h to 12 and 19 at 4 h postinjection. Moreover, this compound has low uptake in bone, displaying the lowest in vivo defluorination among all androgens labeled with fluorine-18 tested so far. The in vive properties of 11 beta-F-DHT in rats are thus favorable for imaging of prostate cancer. On the other hand, 11 beta-F-19-nor-DHT shows low prostate uptake with low selectivity and high uptake in liver, kidney, and bladder. Even though this ligand has the highest RBA and undergoes little metabolic defluorination, it appears to suffer from rapid metabolism in vivo. Therefore, it is apparent that the biodistribution properties of androgens are affected by their structure and metabolism as well as by their RBA.

  DOI：

  10.1021/jm00005a009

文献信息

• Steroid intermediates
  申请人：The University of Sheffield

  公开号：US04882439A1

  公开（公告）日：1989-11-21

  Total synthesis of steroids with substitution in the 2,3, 6, 11 or 17 positions comprising the step of cyclization of a compound having the formula ##STR1## or analogues thereof, where X represents .dbd.O, ##STR2## or .beta.-substituted ##STR3## Y represents .dbd.O, .beta.-oriented ##STR4## or .beta.-orientated OH, R' and R.sup.2 may be the same or different and R' represents alkyl or aryl and R.sup.2 represents alkyl and Z represents ether or hindered ester to form the novel compounds ##STR5##

  在2、3、6、11或17位置带有取代基的类固醇的全合成包括以下步骤：将具有以下公式的化合物或其类似物环化，其中X代表.dbd.O、##STR2##或.beta.-取代的##STR3##，Y代表.dbd.O、.beta.-定向的##STR4##或.beta.-定向的OH，R'和R.sup.2可以相同也可以不同，其中R'代表烷基或芳基，R.sup.2代表烷基，Z代表醚或阻碍酯，以形成新化合物##STR5##。
• Synthesis of steroids and intermediates therof
  申请人：THE UNIVERSITY OF SHEFFIELD

  公开号：EP0216614A2

  公开（公告）日：1987-04-01

  Total synthesis of steroids with substitution in the 2,3, 6, 11 or 17 positions comprising the step of cyclization of a compound having the formula or analogues thereof where X represents Y represents =0, β-orientated β-orientated OH, R'and R2 may be the same or different and R' represents alkyl or aryl and R2 represents alkyl and Z represents ether or hindered ester to form the novel compounds

  在 2、3、6、11 或 17 位上具有取代作用的类固醇的全合成，包括具有以下式子的化合物的环化步骤 或其类似物的环化步骤，其中 X 代表 Y 代表 =0、β-取向的 R'和 R2 可以相同或不同，R'代表烷基或芳基，R2 代表烷基，Z 代表醚或受阻酯。
• US4882439A
  申请人：——

  公开号：US4882439A

  公开（公告）日：1989-11-21