6α-benzylandrost-4-ene-3,17-dione | 156264-72-1

• 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-benzylandrost-4-ene-3,17-dione
• 英文别名: (6R,8R,9S,10R,13S,14S)-6-benzyl-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene-3,17-dione
• CAS: 156264-72-1
• 化学式: C₂₆H₃₂O₂
• 分子量: 376.539
• InChiKey: GOFPYVGJAASCMJ-YSOVCADESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.62
• 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：

  6α-benzylandrost-4-ene-3,17-dione 在 四氯苯醌 、 对甲苯磺酸 作用下， 以 xylene 为溶剂， 反应 3.0h， 以84%的产率得到6-benzylandrosta-4,6-diene-3,17-dione
  参考文献：
  名称：

  具有 1,4-二烯、4,6-二烯或 1,4,6-三烯结构的 6-苯基脂肪族取代的 C19 类固醇作为芳香酶抑制剂的合成和构效关系

  摘要：

  一系列 6alpha- 和 6beta-苯基脂肪族取代的 androsta-1,4-diene-3,17-diones [9b-f 和 10b-f; (CH2)nPh, n = 1-5] 和它们的 4,6-二烯和 1,4,6-三烯类似物（11b-f 和 12b-f）以及它们各自的苯基类似物 9a-12a 被合成和测试为芳香酶抑制剂。所有检查的类固醇都是人胎盘微粒体中芳香酶的非常强大的竞争性抑制剂，其表观 Ki 值范围为 8.5 至 80 nM。苄基-和苯乙基-4,6-二烯 11b 和 11c（Ki，9.0 和 10 nM）以及 6-苯乙基-1,4,6-三烯 12c（Ki，8.5 nM）的抑制活性极强其中高。除了 6β-苯乙基化合物 10c 和 6-苯基-4,6-二烯 11a 外，所有的苯脂肪族类固醇对芳香酶的亲和力都高于相应的母体 1,4-二烯、4,6-二烯和 1 ,4, 6-三烯类固醇 9g、11g

  DOI：

  10.1016/s0039-128x(98)00088-9
• 作为产物：
  描述：

  苄基溴化镁 在 吡啶 、 盐酸 、 氯化亚砜 、 高氯酸 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 9.05h， 生成 6α-benzylandrost-4-ene-3,17-dione
  参考文献：
  名称：

  6-Alkyl- and 6-Arylandrost-4-ene-3,17-diones as Aromatase Inhibitors. Synthesis and Structure-Activity Relationships

  摘要：

  Two series of 6 beta- and 6 alpha-substituted androst-4-ene-3,17-diones (5 and 6) were synthesized as aromatase inhibitors to gain insights of structure-activity relationships of varying substituents (methyl, ethyl, n-propyl, isopropyl, n-butyl, phenyl, benzyl, vinyl, and ethynyl) to the inhibitory activity. All of the inhibitors synthesized prevented human placental aromatase in a competitive manner. The inhibition activities of all the 6-n-alkylated steroids 5a-d and 6a-d (K-i = 1.4-12 nM) as well as the 6 beta-vinyl (5h), 6 alpha-benzyl (6g), and 6-methylene (10) compounds (K-i = 5.1, 10, and 4.9 nM, respectively) were very powerful whereas those of the g-isopropyl (5e and 6e), 6-phenyl (5f and 6f), 6 beta-benzyl (5g), and 6 beta-ethynyl (5i) steroids, having a bulky or polar substituent, were relatively weak. The 6 beta-ethyl derivative 5b was the most potent inhibitor among those synthesized. Inhibitors 5a, 5f, 5h, 5i, 6b, and 10 did not cause a time-dependent inactivation of aromatase. The 6 beta-alkyl steroids essentially had higher affinity for the enzyme than the corresponding 6 alpha-isomers, whereas the opposite relation was observed in a series of the aryl steroids. These results along with molecular modeling with the PM3 method clearly indicate that aromatase has a hydrophobic binding pocket with a limited accessible volume in the active site in the region corresponding to the beta-side rather than the alpha-side of the C-6 position of the substrate.

  DOI：

  10.1021/jm00035a011