4-(methylthio)androst-4-ene-3,17-dione | 100513-89-1

• 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: 4-(methylthio)androst-4-ene-3,17-dione
• 英文别名: (8R,9S,10R,13S,14S)-10,13-dimethyl-4-methylsulfanyl-2,6,7,8,9,11,12,14,15,16-decahydro-1H-cyclopenta[a]phenanthrene-3,17-dione
• CAS: 100513-89-1
• 化学式: C₂₀H₂₈O₂S
• 分子量: 332.507
• InChiKey: BZYIICZUVPPSEB-PFIYWFKMSA-N

物化性质

• 沸点：
  489.8±45.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  59.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4,5-epoxyandrostane-3,17-dione 在 盐酸 、 potassium tert-butylate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 为溶剂， 反应 158.08h， 生成 4-(methylthio)androst-4-ene-3,17-dione
  参考文献：
  名称：

  Synthesis and evaluation of a new series of mechanism-based aromatase inhibitors

  摘要：

  A series of new 4-(alkylthio)-substituted androstenedione analogues was designed as potential suicide inhibitors of aromatase on the basis of mechanistic considerations on the mode of action of the enzyme. Their synthesis and biological evaluation are described. Among the most interesting are the 4-[(difluoromethyl)thio]-, 4-[(fluoromethyl) thio]-, and 4-[(chloromethyl)thio]androstenediones 12,13, and 14 with respective IC50's of 2.7,0.8, and 0.94-mu-M. Compound 12 was a reversible inhibitor of aromatase while compounds 13 and 14 displayed time-dependent kinetics of inhibition with respective K(I)'s and half-times of inactivation of 30 nM and 3.75 min for 13 and 30 nM and 3 min for 14. The inhibition of aromatase by 14 was NADPH-dependent, and was protected by the presence of substrate (0.5-1-mu-M), while beta-mercaptoethanol (0.5 mM) failed to protect the enzyme from inactivation. Dialysis failed to reactivate aromatase previously inactivated by 14. The mechanistic implications of these findings are

  DOI：

  10.1021/jm00087a013

文献信息

• Synthesis and evaluation of 4-(substituted thio)-4-androstene-3,17-dione derivatives as potential aromatase inhibitors
  作者：Yusuf J. Abul-Hajj

  DOI：10.1021/jm00154a025

  日期：1986.4

  The synthesis and evaluation of 4-(substituted thio)-4-androstene-3,17-dione derivatives as inhibitors of estrogen synthetase (aromatase) are described. All compounds were prepared by the addition of various thiol reagents to 4 beta,5 beta-epoxyandrostanedione. Inhibitory activity of synthesized compounds was determined with use of a human placental microsomal preparation as the enzyme source and [1

  描述了作为雌激素合成酶（芳香酶）抑制剂的4-（取代硫代）-4-雄烯-3,17-二酮衍生物的合成和评价。通过将各种硫醇试剂添加到4 beta，5β-环氧雄烷二酮中来制备所有化合物。以人胎盘微粒体制剂为酶源，以[1β-3H] -4-雄烯酮-3,17-二酮为底物，测定合成化合物的抑制活性。在初始速度条件下进一步评估了表现出高抑制活性的合成化合物，以确定表观Ki值。几种化合物是有效的竞争性抑制剂，其表观Ki值范围为36至73 nM，雄烯二酮的表观Km为53 nM。