6α-methylandrosta-1,4-diene-3,17-dione

• 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: 6α-methylandrosta-1,4-diene-3,17-dione
• 英文别名: 6alpha-Methyl-1,4-androstadiene-3,17-dione；(6S,8R,9S,10R,13S,14S)-6,10,13-trimethyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene-3,17-dione
• 化学式: C₂₀H₂₆O₂
• 分子量: 298.425
• InChiKey: BWNQBQAKVQVBHH-JKNDIDBPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 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：

  3,17-Dioxo-7α-methylandrosta-1,4-dien 、 6α-methylandrosta-1,4-diene-3,17-dione 、 雄甾-1,4-二烯-3,17-二酮 以above results in the preparation of 7α-methyl-1β,2β-methylene-4-androstene-3,17-dione and 6α-methyl-1β,2β-methylene-4-androstene-3,17-dione的产率得到7alpha-Methyl-1beta,2beta-methylene-4-androstene-3,17-dione
  参考文献：
  名称：

  19-Oxygenated-5.alpha.-androstanes for the enhancement of libido

  摘要：

  本文描述了19-氧化-5α-雄甾烷衍生物，可用于增强哺乳动物的性欲和相关的心理态度。

  公开号：

  US04071625A1
• 作为产物：
  描述：

  雄烯二酮 在 palladium on activated charcoal 2,3-二氯-5,6-二氰基-1,4-苯醌 、 苯甲醇 、 环己烯 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 生成 6α-methylandrosta-1,4-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

• Time-Dependent Inactivation of Aromatase by 6-Alkylandrosta-1,4-diene-3,17-diones. Effects of Length and Configuration of the 6-Alkyl Group
  作者：Mitsuteru Numazawa、Mariko Oshibe、Satoshi Yamaguchi、Mii Tachibana

  DOI：10.1021/jm950720u

  日期：1996.1.1

  structure-activity relationship of varying the 6-n-alkyl substituents (C-1--C-7) to the time-dependent inactivation activity. All of the inhibitors synthesized were powerful to good competitive inhibitors of aromatase, with apparent Ki's ranging from 4.7 to 54 nM. The 6beta-ethyl (4b) and 6beta-n-pentyl (4e) compounds were the most potent among them (Ki = 4.7 and 5.0 nM for 4b and 4e, respectively).

  合成了一系列6α-和6β-烷基雄甾烯-1,4-二烯-3,17-二酮（3和4），并作为人类胎盘微粒体中芳香化酶的时间依赖性灭活剂进行了评估，以了解其结构活性关系。将6-正烷基取代基（C-1--C-7）改变为随时间变化的灭活活性。合成的所有抑制剂均是芳香酶的良好竞争抑制剂，其表观Ki范围为4.7至54 nM。6beta-乙基（4b）和6beta-n-戊基（4e）化合物是其中最有效的化合物（4b和4e的Ki分别为4.7和5.0 nM）。在一系列的6-α-烷基甾族化合物中，在6-位具有C-1--C-4的抑制剂3a-d以及6个α-正庚基（3g）化合物没有。相反，在6β-烷基甾族化合物系列中，只有甲基类似物4a会以时间依赖性方式使芳香化酶失活，而在C-6beta处具有两个以上碳原子的其他烷基类固醇则没有。底物雄烯二酮可防止失活，并且在每种情况下均未观察到L-半胱氨酸对失活的显着影响。这些结果以及使用P
• Androst-4-en-19-ones
  申请人：Richardson-Merrell Inc.

  公开号：US04022769A1

  公开（公告）日：1977-05-10

  The present invention concerns derivatives of androst-4-en-19-one which are useful in the enhancement of libido and related psychic attitudes.

  本发明涉及雄甾-4-烯-19-酮的衍生物，其在增强性欲和相关的心理态度方面有用。
• 19-Oxygenated-5.alpha.-androstanes for the enhancement of libido
  申请人：Richardson-Merrell Inc.

  公开号：US04071625A1

  公开（公告）日：1978-01-31

  Derivatives of 19-oxygenated-5.alpha.-androstanes are described which are useful in enhancing the libido and related psychic attitudes in mammals.

  本文描述了19-氧化-5α-雄甾烷衍生物，可用于增强哺乳动物的性欲和相关的心理态度。
• RING, S.;STOPSACK, H.;SCHWARZ, S., CHEMIEDOZENTENTAG., 1988, LEIPZIG, 23-25 MARZ, 1988, BERLIN,(S. A.) C. 32
  作者：RING, S.、STOPSACK, H.、SCHWARZ, S.

  DOI：——

  日期：——
• US4022769A
  申请人：——

  公开号：US4022769A

  公开（公告）日：1977-05-10