17β-toluenesulfonyloxy-estra-1,3,5(10)-trien-3-ol | 119074-05-4

• 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: 17β-toluenesulfonyloxy-estra-1,3,5(10)-trien-3-ol
• 英文别名: 17β-(toluene-sulfonyl-(4)-oxy)-estratrien-(1,3,5(10))-ol-(3)；17β-(Toluol-sulfonyl-(4)-oxy)-oestratrien-(1,3,5(10))-ol-(3)；[(8R,9S,13S,14S,17S)-3-hydroxy-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthren-17-yl] 4-methylbenzenesulfonate
• CAS: 119074-05-4
• 化学式: C₂₅H₃₀O₄S
• 分子量: 426.577
• InChiKey: FKBGHOIYIHEXNW-VAFBSOEGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  72
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-O-苄基雌酮 在 吡啶 、 sodium tetrahydroborate 、 氢气 、 palladium(II) hydroxide 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 乙酸乙酯 为溶剂， 反应 17.0h， 生成 17β-toluenesulfonyloxy-estra-1,3,5(10)-trien-3-ol
  参考文献：
  名称：

  17β-Arylsulfonamides of 17β-aminoestra-1,3,5(10)-trien-3-ol as highly potent inhibitors of steroid sulfatase

  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 and other steroid-dependent cancers. Here we report the synthesis of a series of 17 beta-arylsulfonamides of 17 beta-aminoestra-1,3,5(10)-trien-3-ol and their evaluation as inhibitors of STS. Some of these compounds are among the most potent reversible STS inhibitors reported to date. Introducing n-alkyl groups into the 4'-position of the 17 beta-benzenesulfonamide derivative resulted in an increase in potency with the n-butyl derivative exhibiting the best potency with an IC50 of 26 nM. A further increase in carbon units (to n-pentyl) resulted in a decrease in potency. Branching of the 4'-n-propyl group resulted in a decrease in potency while branching of the 4'-n-butyl group (to a tert-butyl group) resulted in a slight increase in potency (IC50 = 18 nM). Studies with 30- and 40-substituted substituted 17 beta-benzenesulfonamides with small electron donating and electron withdrawing groups revealed the 3'-bromo and 3'-trifluoromethyl derivatives to be excellent inhibitors with IC50's of 30 and 23 nM, respectively. The 17 beta-2'-naphthalenesulfonamide was also an excellent inhibitor (IC50 = 20 nM) while the 17 beta-4'-phenylbenzenesulfonamide derivative was the most potent inhibitor of all the compounds studied with an IC50 of 9 nM. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.12.036

文献信息

• α-Oestradiol Dimethyl Ether, 17-Monomethyl Ether, and Related Compounds
  作者：Yoshiyuki Urushibara、Takesi Nitta

  DOI：10.1246/bcsj.16.179

  日期：1941.6
• 17-thio derivatives of estratrien-3-ol and of estratetraen-3-ol
  申请人：SEARLE &

  公开号：US02840577A1

  公开（公告）日：1958-06-24
• 17β-Arylsulfonamides of 17β-aminoestra-1,3,5(10)-trien-3-ol as highly potent inhibitors of steroid sulfatase
  作者：Yaser A. Mostafa、Scott D. Taylor

  DOI：10.1016/j.bmc.2011.12.036

  日期：2012.2

  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 and other steroid-dependent cancers. Here we report the synthesis of a series of 17 beta-arylsulfonamides of 17 beta-aminoestra-1,3,5(10)-trien-3-ol and their evaluation as inhibitors of STS. Some of these compounds are among the most potent reversible STS inhibitors reported to date. Introducing n-alkyl groups into the 4'-position of the 17 beta-benzenesulfonamide derivative resulted in an increase in potency with the n-butyl derivative exhibiting the best potency with an IC50 of 26 nM. A further increase in carbon units (to n-pentyl) resulted in a decrease in potency. Branching of the 4'-n-propyl group resulted in a decrease in potency while branching of the 4'-n-butyl group (to a tert-butyl group) resulted in a slight increase in potency (IC50 = 18 nM). Studies with 30- and 40-substituted substituted 17 beta-benzenesulfonamides with small electron donating and electron withdrawing groups revealed the 3'-bromo and 3'-trifluoromethyl derivatives to be excellent inhibitors with IC50's of 30 and 23 nM, respectively. The 17 beta-2'-naphthalenesulfonamide was also an excellent inhibitor (IC50 = 20 nM) while the 17 beta-4'-phenylbenzenesulfonamide derivative was the most potent inhibitor of all the compounds studied with an IC50 of 9 nM. (C) 2012 Elsevier Ltd. All rights reserved.