4-<(chloromethyl)thio>androsta-4,9(11)-diene-3,17-dione | 140111-63-3

• 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-<(chloromethyl)thio>androsta-4,9(11)-diene-3,17-dione
• 英文别名: 4-[(chloromethyl)thio]androsta-4,9(11)-diene-3,17-dione；(8S,10R,13S,14S)-4-(chloromethylsulfanyl)-10,13-dimethyl-2,6,7,8,12,14,15,16-octahydro-1H-cyclopenta[a]phenanthrene-3,17-dione
• CAS: 140111-63-3
• 化学式: C₂₀H₂₅ClO₂S
• 分子量: 364.936
• InChiKey: IJJJTAZQYVCQBF-ICCDWZQGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.7
• 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：

  Thioacetic acid S-((8S,10R,13S,14S)-5-hydroxy-10,13-dimethyl-3,17-dioxo-2,3,4,5,6,7,8,10,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-4-yl) ester 在 盐酸 、 potassium tert-butylate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 38.08h， 生成 4-<(chloromethyl)thio>androsta-4,9(11)-diene-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