4-formyl-2-bromo-3-hydroxyestra-1,3,5(10)-trien-17-one | 1338811-74-7

• 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-formyl-2-bromo-3-hydroxyestra-1,3,5(10)-trien-17-one
• 英文别名: (8R,9S,13S,14S)-2-bromo-3-hydroxy-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene-4-carbaldehyde
• CAS: 1338811-74-7
• 化学式: C₁₉H₂₁BrO₃
• 分子量: 377.278
• InChiKey: QXAZQEYPCWESLS-RHQBZFHZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  23
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  54.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (8R,9S,13S,14S)-3-hydroxy-13-methyl-17-oxo-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthrene-4-carbaldehyde 在 N-溴代乙酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 以94%的产率得到4-formyl-2-bromo-3-hydroxyestra-1,3,5(10)-trien-17-one
  参考文献：
  名称：

  Inhibition of steroid sulfatase with 4-substituted estrone and estradiol derivatives

  摘要：

  Steroid sulfatase (STS) catalyzes the desulfation of biologically inactive sulfated steroids to yield biologically active desulfated steroids and is currently being examined as a target for therapeutic intervention for the treatment of breast cancer. We previously demonstrated that 4-formyl estrone is a time- and concentration-dependent inhibitor of STS. We have prepared a series of 4-formylated estrogens and examined them as irreversible STS inhibitors. Introducing a formyl, bromo or nitro group at the 2-position of 4-formylestrone resulted in loss of concentration and time-dependent inhibition and a considerable decrease in binding affinity. An estradiol derivative bearing a formyl group at the 4-position and a benzyl group at the 17 beta-position yielded a potent concentration and time-dependent STS inhibitor with a K-l of 85 nM and a k(inact) of 0.021 min(-1) (k(inact)/K-l of 2.3 x 10(5) M-1 min(-1)). Studies with estrone or estradiol substituted at the 4-position with groups other than a formyl group revealed that good reversible inhibitors can be obtained by introducing small electron withdrawing groups at this position. An estradiol derivative with fluorine at the 4-position and a benzyl group at the 17 beta-position yielded a potent, reversible inhibitor of STS with an IC50 of 40 nM. The introduction of relatively small electron withdrawing groups at the 4-position of estrogens and their derivatives may prove to be a general approach to enhancing the potency of estrogen-derived STS inhibitors. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.08.046

文献信息

• Inhibition of steroid sulfatase with 4-substituted estrone and estradiol derivatives
  作者：Chau-Minh Phan、Yong Liu、Byoung-moo Kim、Yaser Mostafa、Scott D. Taylor

  DOI：10.1016/j.bmc.2011.08.046

  日期：2011.10

  Steroid sulfatase (STS) catalyzes the desulfation of biologically inactive sulfated steroids to yield biologically active desulfated steroids and is currently being examined as a target for therapeutic intervention for the treatment of breast cancer. We previously demonstrated that 4-formyl estrone is a time- and concentration-dependent inhibitor of STS. We have prepared a series of 4-formylated estrogens and examined them as irreversible STS inhibitors. Introducing a formyl, bromo or nitro group at the 2-position of 4-formylestrone resulted in loss of concentration and time-dependent inhibition and a considerable decrease in binding affinity. An estradiol derivative bearing a formyl group at the 4-position and a benzyl group at the 17 beta-position yielded a potent concentration and time-dependent STS inhibitor with a K-l of 85 nM and a k(inact) of 0.021 min(-1) (k(inact)/K-l of 2.3 x 10(5) M-1 min(-1)). Studies with estrone or estradiol substituted at the 4-position with groups other than a formyl group revealed that good reversible inhibitors can be obtained by introducing small electron withdrawing groups at this position. An estradiol derivative with fluorine at the 4-position and a benzyl group at the 17 beta-position yielded a potent, reversible inhibitor of STS with an IC50 of 40 nM. The introduction of relatively small electron withdrawing groups at the 4-position of estrogens and their derivatives may prove to be a general approach to enhancing the potency of estrogen-derived STS inhibitors. (C) 2011 Elsevier Ltd. All rights reserved.