16α,17α-<(R)-(1'-α-furylethylidene)dioxy>-21-<<(trifluoromethyl)sulfonyl>oxy>-19-norpregn-4-ene-3,20-dione | 160388-41-0

• 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: 16α,17α-<(R)-(1'-α-furylethylidene)dioxy>-21-<<(trifluoromethyl)sulfonyl>oxy>-19-norpregn-4-ene-3,20-dione
• 英文别名: [2-[(1R,2S,4R,6R,8S,9S,12S,13R)-6-(furan-2-yl)-6,9-dimethyl-16-oxo-5,7-dioxapentacyclo[10.8.0.02,9.04,8.013,18]icos-17-en-8-yl]-2-oxoethyl] trifluoromethanesulfonate
• CAS: 160388-41-0
• 化学式: C₂₇H₃₁F₃O₈S
• 分子量: 572.6
• InChiKey: ZHYJIRJCXKRUBZ-OGWBNBMISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  39
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  118
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  16α,17α-<(R)-(1'-α-furylethylidene)dioxy>-21-<<(trifluoromethyl)sulfonyl>oxy>-19-norpregn-4-ene-3,20-dione 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 0.83h， 以25%的产率得到21-fluoro-16α,17α-<(R)-(1'-α-furylethylidene)dioxy>-19-norpregn-4-ene-3,20-dione
  参考文献：
  名称：

  Fluorine-18-labeled progestin 16.alpha.,17.alpha.-dioxolanes: development of high-affinity ligands for the progesterone receptor with high in vivo target site selectivity

  摘要：

  We describe the synthesis and tissue biodistribution of two 21-[fluoro-F-18]progestin 16 alpha,17 alpha-furanyl ketals, potential agents for imaging progesterone receptor (PR)-positive breast tumors in humans, using positron emission tomography. 21-Fluoro-16 alpha,17 alpha-[(R)-(1'-alpha-furyl-methylidene)dioxy]-19-norpregn-4-ene-3,20-dione (endo-10a) and 21-fluoro-16 alpha,17 alpha-[(R)-(1'-alpha-furylethylidene) dioxy]-19-norpregn-4-ene-3,20-dione (endo-10b) were chosen for radiochemical synthesis from a series of seven novel progestin 16 alpha,17 alpha-(furanyldioxolanes) on the basis of their high relative binding affinity to PR (190% and 173%, respectively, relative to R5020 = 100%), their low nonspecific binding (NSB) (log P-o/w = 3.87 and 4.13, respectively), and their resulting high binding selectivity indices (BSI; i.e., the ratio of their PR binding affinity to nonspecific binding). Radiochemical synthesis of these two species in high radiochemical purity and at high effective specific activity was accomplished by treatment of the corresponding diastereomerically pure 21-trifluoromethanesulfonates with fluorine-18 anion. In tissue biodistribution studies in estrogen-primed immature female Sprague-Dawley rats, both [F-18]-endo-10a and [F-18]endo-10b demonstrated high PR-selective uptake in the principal target tissues, the uterus and the ovaries, and relatively low uptake in fat and bone. The metabolism at the 21-position in these progestins (as monitored by in vivo defluorination) appears to be less than that in other 21-fluoroprogestins; this may reflect steric inhibition of metabolism at this site due to the bulk of the furan-substituted dioxolane ring at the 16 alpha,17 alpha-position. Comparison with other fluorine-18-labeled progestins shows that the PR-specific uptake in uterine tissue correlates with the BSI of the ligand and that the fat uptake correlates with the NSB of the ligand at high levels of statistical significance. These two dioxolanes may prove to be useful as breast tumor-imaging agents in humans.

  DOI：

  10.1021/jm00002a014
• 作为产物：
  描述：

  16α,17α,21-trihydroxy-19-norpregn-4-ene-3,20-dione 在 2,6-二甲基吡啶 、 高氯酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.25h， 生成 16α,17α-<(R)-(1'-α-furylethylidene)dioxy>-21-<<(trifluoromethyl)sulfonyl>oxy>-19-norpregn-4-ene-3,20-dione
  参考文献：
  名称：

  Fluorine-18-labeled progestin 16.alpha.,17.alpha.-dioxolanes: development of high-affinity ligands for the progesterone receptor with high in vivo target site selectivity

  摘要：

  We describe the synthesis and tissue biodistribution of two 21-[fluoro-F-18]progestin 16 alpha,17 alpha-furanyl ketals, potential agents for imaging progesterone receptor (PR)-positive breast tumors in humans, using positron emission tomography. 21-Fluoro-16 alpha,17 alpha-[(R)-(1'-alpha-furyl-methylidene)dioxy]-19-norpregn-4-ene-3,20-dione (endo-10a) and 21-fluoro-16 alpha,17 alpha-[(R)-(1'-alpha-furylethylidene) dioxy]-19-norpregn-4-ene-3,20-dione (endo-10b) were chosen for radiochemical synthesis from a series of seven novel progestin 16 alpha,17 alpha-(furanyldioxolanes) on the basis of their high relative binding affinity to PR (190% and 173%, respectively, relative to R5020 = 100%), their low nonspecific binding (NSB) (log P-o/w = 3.87 and 4.13, respectively), and their resulting high binding selectivity indices (BSI; i.e., the ratio of their PR binding affinity to nonspecific binding). Radiochemical synthesis of these two species in high radiochemical purity and at high effective specific activity was accomplished by treatment of the corresponding diastereomerically pure 21-trifluoromethanesulfonates with fluorine-18 anion. In tissue biodistribution studies in estrogen-primed immature female Sprague-Dawley rats, both [F-18]-endo-10a and [F-18]endo-10b demonstrated high PR-selective uptake in the principal target tissues, the uterus and the ovaries, and relatively low uptake in fat and bone. The metabolism at the 21-position in these progestins (as monitored by in vivo defluorination) appears to be less than that in other 21-fluoroprogestins; this may reflect steric inhibition of metabolism at this site due to the bulk of the furan-substituted dioxolane ring at the 16 alpha,17 alpha-position. Comparison with other fluorine-18-labeled progestins shows that the PR-specific uptake in uterine tissue correlates with the BSI of the ligand and that the fat uptake correlates with the NSB of the ligand at high levels of statistical significance. These two dioxolanes may prove to be useful as breast tumor-imaging agents in humans.

  DOI：

  10.1021/jm00002a014

文献信息

• Fluorine-18-labeled progestin 16.alpha.,17.alpha.-dioxolanes: development of high-affinity ligands for the progesterone receptor with high in vivo target site selectivity
  作者：Brad O. Buckman、Thomas A. Bonasera、Karen S. Kirschbaum、Michael J. Welch、John A. Katzenellenbogen

  DOI：10.1021/jm00002a014

  日期：1995.1

  We describe the synthesis and tissue biodistribution of two 21-[fluoro-F-18]progestin 16 alpha,17 alpha-furanyl ketals, potential agents for imaging progesterone receptor (PR)-positive breast tumors in humans, using positron emission tomography. 21-Fluoro-16 alpha,17 alpha-[(R)-(1'-alpha-furyl-methylidene)dioxy]-19-norpregn-4-ene-3,20-dione (endo-10a) and 21-fluoro-16 alpha,17 alpha-[(R)-(1'-alpha-furylethylidene) dioxy]-19-norpregn-4-ene-3,20-dione (endo-10b) were chosen for radiochemical synthesis from a series of seven novel progestin 16 alpha,17 alpha-(furanyldioxolanes) on the basis of their high relative binding affinity to PR (190% and 173%, respectively, relative to R5020 = 100%), their low nonspecific binding (NSB) (log P-o/w = 3.87 and 4.13, respectively), and their resulting high binding selectivity indices (BSI; i.e., the ratio of their PR binding affinity to nonspecific binding). Radiochemical synthesis of these two species in high radiochemical purity and at high effective specific activity was accomplished by treatment of the corresponding diastereomerically pure 21-trifluoromethanesulfonates with fluorine-18 anion. In tissue biodistribution studies in estrogen-primed immature female Sprague-Dawley rats, both [F-18]-endo-10a and [F-18]endo-10b demonstrated high PR-selective uptake in the principal target tissues, the uterus and the ovaries, and relatively low uptake in fat and bone. The metabolism at the 21-position in these progestins (as monitored by in vivo defluorination) appears to be less than that in other 21-fluoroprogestins; this may reflect steric inhibition of metabolism at this site due to the bulk of the furan-substituted dioxolane ring at the 16 alpha,17 alpha-position. Comparison with other fluorine-18-labeled progestins shows that the PR-specific uptake in uterine tissue correlates with the BSI of the ligand and that the fat uptake correlates with the NSB of the ligand at high levels of statistical significance. These two dioxolanes may prove to be useful as breast tumor-imaging agents in humans.