6-methylandrosta-4,6-diene-3,17-dione | 17183-96-9

• 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: 6-methylandrosta-4,6-diene-3,17-dione
• 英文别名: (8R,9S,10R,13S,14S)-6,10,13-trimethyl-2,8,9,11,12,14,15,16-octahydro-1H-cyclopenta[a]phenanthrene-3,17-dione
• CAS: 17183-96-9
• 化学式: C₂₀H₂₆O₂
• 分子量: 298.425
• InChiKey: LPMDCPLRVPBTRF-DAELLWKTSA-N

物化性质

• 熔点：
  164 °C
• 沸点：
  450.2±45.0 °C(Predicted)
• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  34.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-methylandrosta-4,6-diene-3,17-dione 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 1,4-二氧六环 为溶剂， 反应 15.0h， 以50%的产率得到6α-methylandrosta-1,4,6-triene-3,17-dione
  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：

  雄烯二酮 在 palladium on activated charcoal 苯甲醇 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 生成 6-methylandrosta-4,6-diene-3,17-dione
  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

• Modified steroid hormones—XXXIX
  作者：G. Cooley、B. Ellis、V. Petrow

  DOI：10.1016/s0040-4020(01)98646-6

  日期：1965.1

  Steroidal 3-alkoxy-6-methyl-3,5,7-trienes have been prepared and hydrolysed to the corresponding 6α-methyl-4,7-dien-3-ones.

  制备了甾族3-烷氧基-6-甲基-3,5,7-三烯并将其水解为相应的6α-甲基-4,7-dien-3-one。
• Process for preparing 16-methylene steroids
  申请人：The Upjohn Company

  公开号：US04416821A1

  公开（公告）日：1983-11-22

  A process is disclosed for the production of 17-keto-16-methylene steroids (III) from the corresponding readily available 17-keto steroid (I) via a novel intermediate (II).

  本发明公开了一种从相应易得的17-酮类固醇(I)经过新型中间体(II)生产17-酮基-16-亚甲基类固醇(III)的方法。
• Inhibitors of type 5 and type 3 17beta-hydroxysteroid dehydrogenase and methods for their use
  申请人：Endorecherche, Inc.

  公开号：US20040082556A1

  公开（公告）日：2004-04-29

  Novel methods of medical treatment and/or inhibition of development of diseases are disclosed for diseases that are sensitive to androgenic or estrogenic activity. The treatments utilize inhibitors of type 5 and/or type 3 17&bgr;-hydroxysteroid dehydrogenase. Novel inhibitors of type 5 17&bgr;-hydroxysteroid dehydrogenase are also disclosed, as are novel inhibitors of type 3 17&bgr;-hydroxysteroid dehydrogenase.

  本发明揭示了一种针对对雄激素或雌激素活性敏感的疾病的新型医疗治疗和/或抑制疾病发展的方法。这些治疗方法利用了类型5和/或类型3的17β-羟基类固醇脱氢酶的抑制剂。本发明还揭示了新型的类型5 17β-羟基类固醇脱氢酶抑制剂，以及新型的类型3 17β-羟基类固醇脱氢酶抑制剂。
• 16-Methylene-17.alpha.-hydroxy-progesterones
  申请人：The Upjohn Company

  公开号：US04567001A1

  公开（公告）日：1986-01-28

  16-Methylene-17-keto steroids (III) are transformed to the corresponding 16-methylene-17.alpha.-hydroxyprogesterones (VII) which are intermediates useful in the production of betamethasone, diflorasone diacetate and melengesterol acetate.

  16-亚甲基-17-酮类固醇（III）被转化为相应的16-亚甲基-17α-羟基孕酮（VII），这些中间体在贝塔甲酸、二氟松醋酸盐和美林松醋酸盐的生产中很有用。
• 16-methylene-steroids and their preparation
  申请人：THE UPJOHN COMPANY

  公开号：EP0104054A2

  公开（公告）日：1984-03-28

  16-Methylene-17-keto-steroids are transformed to the corresponding 16-methylene-17a-hydroxyprogesterones which are intermediates useful in the production of betamethasone, diflorasone diacetate and melengesterol acetate. 17a-Hydroxy-6, 16-dimethylene-pregn-4-ene-3, 20-dione is simultaneously isomerized and acylated to 17a-hydroxy-6-methyl-16-methylenepregna-4, 6-diene-3, 20-dione 17-acetate.

  16-亚甲基-17-酮类类固醇可转化为相应的 16-亚甲基-17a-羟基黄体酮，这些黄体酮是生产倍他米松、双醋酸地氟松和醋酸美伦孕酮的中间体。17a-羟基-6，16-二亚甲基孕甾-4-烯-3，20-二酮同时异构化和酰化为 17a-羟基-6-甲基-16-亚甲基孕甾-4，6-二烯-3，20-二酮 17-乙酸酯。