6-methoxy-4,6-androstadiene-3,17-dione | 103232-93-5

• 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-methoxy-4,6-androstadiene-3,17-dione
• 英文别名: (8R,9S,10R,13S,14S)-6-methoxy-10,13-dimethyl-2,8,9,11,12,14,15,16-octahydro-1H-cyclopenta[a]phenanthrene-3,17-dione
• CAS: 103232-93-5
• 化学式: C₂₀H₂₆O₃
• 分子量: 314.425
• InChiKey: SVHKJDRBSUITJR-HQNIOCCESA-N

物化性质

• 沸点：
  482.7±45.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-methoxy-4,6-androstadiene-3,17-dione 在 盐酸 、 对甲苯磺酸 作用下， 以 二氯甲烷 、 苯 为溶剂， 反应 78.0h， 生成 3,3-diethylthio-4-androstene-6,17-dione
  参考文献：
  名称：

  Numazawa, Mitsuteru; Tsuji, Masachika; Osada, Ryoko, Journal of Chemical Research, Miniprint, 1986, # 2, p. 718 - 734

  摘要：

  DOI：
• 作为产物：
  描述：

  雄甾-4-烯-3β,6β,17β-三醇 在 甲醇 、 碳酸氢钠 、 对甲苯磺酸 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 27.0h， 生成 6-methoxy-4,6-androstadiene-3,17-dione
  参考文献：
  名称：

  Numazawa, Mitsuteru; Tsuji, Masachika; Osada, Ryoko, Journal of Chemical Research, Miniprint, 1986, # 2, p. 718 - 734

  摘要：

  DOI：

文献信息

• Probing the binding pocket of the active site of aromatase with 6-ether or 6-ester substituted androst-4-ene-3,17-diones and their diene and triene analogs
  作者：Mitsuteru Numazawa、Momoko Shelangouski、Mina Nagasaka

  DOI：10.1016/s0039-128x(00)00169-0

  日期：2000.12

  A series of 6-ester- (3 and 4) and 6-ether- (7 and 8) substituted androst-4-ene-3,17-diones (androstenediones) and their 1,4-diene analogs (5 and 6, and 9 and 10) as well as CB-substituted 4,6-diene and 1,4,6-triene steroids 11 and 12 were synthesized as aromatase inhibitors to gain insight into the structure-activity relationship between various substituents and inhibitory activity. All of the inhibitors synthesized blocked aromatase in a competitive manner. The inhibitory activities of all of the steroids, except for the 6 beta -benzoates 4g and 6h and the 6 beta -acetate 6a, were fairly effective to very powerful (K-i: 7.0 -320 nM). The 6 alpha -n-hexanoyloxy- and 6 alpha -benzyloxyandrostenediones (3e and 7e) were the most potent inhibitors (K-i: 7.0 nM each). In the series of 4-ene and 1,4-diene steroids, the 6 alpha -substituted steroids had higher affinity for the enzyme than the corresponding 6 beta -isomers. In the 1,4-diene steroid series, 6 beta -substituted steroids 6a, e, g, and 10a, b, e caused a time-dependent inactivation of aromatase, whereas their 6 alpha -isomers 5 and 9 essentially did not. The ether-substituted 1,4,6-trienes 12 inactivated the enzyme in a time-dependent manner; in contrast, their 4,6-diene analogs 11 did not. The substrate androstenedione blocked the inactivation, but no significant effect of L-cysteine was observed. Based on molecular modeling with the PM3 method, along with the present inhibition and inactivation results, it is thought that both the steric effects of the 6-substituents as well as the electronic effects of the C-6 oxygen functions play a critical role in the binding of inhibitors to the active site of aromatase. (C) 2000 Elsevier Science Inc. All rights reserved.