(8R,9S,10R,13S,14S)-10,13-二甲基螺[7,8,9,11,12,13,15,16-八氢-6H-环戊并[a]菲-6,2-环氧乙烷]-3,17(10H,14H)-二酮 | 184972-12-1

• 物质功能分类: 生物 - 细胞培养 - 添加剂
• 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
• 中文名称: (8R,9S,10R,13S,14S)-10,13-二甲基螺[7,8,9,11,12,13,15,16-八氢-6H-环戊并[a]菲-6,2-环氧乙烷]-3,17(10H,14H)-二酮
• 中文别名: 螺[雄甾-1,4-二烯-6,2′-噁丙环]-3,17-二酮
• 英文名称: FCE27353
• 英文别名: 6α/β-spirooxiranandrosta-1,4-diene-3,17-dione；Spiro[androsta-1,4-diene-6,2'-oxirane]-3,17-dione；(8R,9S,10R,13S,14S)-10,13-dimethylspiro[7,8,9,11,12,14,15,16-octahydrocyclopenta[a]phenanthrene-6,2'-oxirane]-3,17-dione
• CAS: 184972-12-1
• 化学式: C₂₀H₂₄O₃
• 分子量: 312.409
• InChiKey: GFNJDRLFFJDJAC-YCNUYBHRSA-N

物化性质

• 熔点：
  >122°C (dec.)
• 溶解度：
  可溶于氯仿（少许）、DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  23
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  46.7
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 储存条件：
  室温且干燥

反应信息

• 作为反应物：
  描述：

  (8R,9S,10R,13S,14S)-10,13-二甲基螺[7,8,9,11,12,13,15,16-八氢-6H-环戊并[a]菲-6,2-环氧乙烷]-3,17(10H,14H)-二酮 在 高氯酸 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以42%的产率得到6-羟基-6-(羟基甲基)-雄甾-1,4-二烯-3,17-二酮
  参考文献：
  名称：

  Synthesis and aromatase inhibition by potential metabolites of exemestane (6-methylenandrosta-1,4-diene-3,17-dione)

  摘要：

  Exemestane (6-methylenandrosta-1,4-diene-3,17-dione; FCE 24304) is an orally active irreversible aromatase inhibitor which is in phase II clinical evaluation for the potential therapy of postmenopausal breast cancer. A series of exemestane analogs, with modifications at the 6-methylene group and with additional reduction at the 17-keto group, were synthesized as potential metabolites and tested in vitro for their effect on human placental aromatase. All these new analogs were found to be less potent in inhibiting aromatase than exemestane. The most effective compound was the 17beta-hydroxy-derivative (compound 2), which is 2.6-fold less potent than exemestane [50% inhibitory concentration (IC50) 69 and 27 nM, respectively]. The various C-6 modified derivatives of the 17-oxo series were found to inhibit the aromatase enzyme in the following descending order: 6-methylene (exemestane) > 6-spirooxirane (6) > 6beta-hydroxymethyl (11) > 6-hydroxymethyl (7) > 6beta-carboxy (13), showing IC50 values of 27, 206, 295, 2,300, and 7,200 nM, respectively. The 17beta-hydroxy analogs of some of the above mentioned compounds were also synthesized (3, 4, 12) and found to be 3-8-fold less potent than the corresponding 17-keto analogs.

  DOI：

  10.1016/0039-128x(93)90029-m
• 作为产物：
  描述：

  依西美坦 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 以80%的产率得到(8R,9S,10R,13S,14S)-10,13-二甲基螺[7,8,9,11,12,13,15,16-八氢-6H-环戊并[a]菲-6,2-环氧乙烷]-3,17(10H,14H)-二酮
  参考文献：
  名称：

  Synthesis and aromatase inhibition by potential metabolites of exemestane (6-methylenandrosta-1,4-diene-3,17-dione)

  摘要：

  Exemestane (6-methylenandrosta-1,4-diene-3,17-dione; FCE 24304) is an orally active irreversible aromatase inhibitor which is in phase II clinical evaluation for the potential therapy of postmenopausal breast cancer. A series of exemestane analogs, with modifications at the 6-methylene group and with additional reduction at the 17-keto group, were synthesized as potential metabolites and tested in vitro for their effect on human placental aromatase. All these new analogs were found to be less potent in inhibiting aromatase than exemestane. The most effective compound was the 17beta-hydroxy-derivative (compound 2), which is 2.6-fold less potent than exemestane [50% inhibitory concentration (IC50) 69 and 27 nM, respectively]. The various C-6 modified derivatives of the 17-oxo series were found to inhibit the aromatase enzyme in the following descending order: 6-methylene (exemestane) > 6-spirooxirane (6) > 6beta-hydroxymethyl (11) > 6-hydroxymethyl (7) > 6beta-carboxy (13), showing IC50 values of 27, 206, 295, 2,300, and 7,200 nM, respectively. The 17beta-hydroxy analogs of some of the above mentioned compounds were also synthesized (3, 4, 12) and found to be 3-8-fold less potent than the corresponding 17-keto analogs.

  DOI：

  10.1016/0039-128x(93)90029-m

文献信息

• Synthesis and aromatase inhibition by potential metabolites of exemestane (6-methylenandrosta-1,4-diene-3,17-dione)
  作者：Franco Buzzetti、Enrico Di Salle、Antonio Longo、Gabriella Briatico

  DOI：10.1016/0039-128x(93)90029-m

  日期：1993.11

  Exemestane (6-methylenandrosta-1,4-diene-3,17-dione; FCE 24304) is an orally active irreversible aromatase inhibitor which is in phase II clinical evaluation for the potential therapy of postmenopausal breast cancer. A series of exemestane analogs, with modifications at the 6-methylene group and with additional reduction at the 17-keto group, were synthesized as potential metabolites and tested in vitro for their effect on human placental aromatase. All these new analogs were found to be less potent in inhibiting aromatase than exemestane. The most effective compound was the 17beta-hydroxy-derivative (compound 2), which is 2.6-fold less potent than exemestane [50% inhibitory concentration (IC50) 69 and 27 nM, respectively]. The various C-6 modified derivatives of the 17-oxo series were found to inhibit the aromatase enzyme in the following descending order: 6-methylene (exemestane) > 6-spirooxirane (6) > 6beta-hydroxymethyl (11) > 6-hydroxymethyl (7) > 6beta-carboxy (13), showing IC50 values of 27, 206, 295, 2,300, and 7,200 nM, respectively. The 17beta-hydroxy analogs of some of the above mentioned compounds were also synthesized (3, 4, 12) and found to be 3-8-fold less potent than the corresponding 17-keto analogs.