9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carboxylic acid [2-(2-{[(2-(4-methyl-benzyl)-3-(2-hydroxy-ethyl)-3-isobutyl-isoxazolidin-5-ylmethyl)-carbamoyl]-methoxy}-ethoxy)-ethyl]-amide | 1140535-14-3

• 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: 9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carboxylic acid [2-(2-{[(2-(4-methyl-benzyl)-3-(2-hydroxy-ethyl)-3-isobutyl-isoxazolidin-5-ylmethyl)-carbamoyl]-methoxy}-ethoxy)-ethyl]-amide
• 英文别名: (8S,9R,10S,11S,13S,14S,16R,17R)-9-fluoro-11,17-dihydroxy-N-[2-[2-[2-[[(3S,5R)-3-(2-hydroxyethyl)-2-[(4-methylphenyl)methyl]-3-(2-methylpropyl)-1,2-oxazolidin-5-yl]methylamino]-2-oxoethoxy]ethoxy]ethyl]-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthrene-17-carboxamide
• CAS: 1140535-14-3
• 化学式: C₄₅H₆₆FN₃O₉
• 分子量: 812.032
• InChiKey: XZYZCEYDWIEKCX-VNPGNNOGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  58
• 可旋转键数：
  17
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  167
• 氢给体数：
  5
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  、 9-氟-11,17-二羟基-16alpha-甲基-3-氧代雄甾-1,4-二烯-17-羧酸 在 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 2,6-二甲基吡啶 、 N,N-二异丙基乙胺 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 12.25h， 以0.8 mg的产率得到9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carboxylic acid [2-(2-{[(2-(4-methyl-benzyl)-3-(2-hydroxy-ethyl)-3-isobutyl-isoxazolidin-5-ylmethyl)-carbamoyl]-methoxy}-ethoxy)-ethyl]-amide
  参考文献：
  名称：

  Expanding the repertoire of small molecule transcriptional activation domains

  摘要：

  Molecules that can reconstitute the function of transcriptional activators hold enormous potential as therapeutic agents and as mechanistic probes. Previously we described an isoxazolidine bearing functional groups similar to natural transcriptional activators that up-regulates transcription 80-fold at 1 mu M in cell culture. In this study, we analyze analogs of this molecule to define key characteristics of small molecules that function as transcriptional activation domains in cells. Conformational rigidity is an important contributor to function as is an overall amphipathic substitution pattern. Using these criteria, we identified additional molecular scaffolds with excellent (similar to 60-fold) activity as transcriptional activation domains. These results point the way for the creation of new generations of small molecules with this function. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.02.045

文献信息

• Expanding the repertoire of small molecule transcriptional activation domains
  作者：Ryan J. Casey、Jean-Paul Desaulniers、Jonas W. Hojfeldt、Anna K. Mapp

  DOI：10.1016/j.bmc.2008.02.045

  日期：2009.2

  Molecules that can reconstitute the function of transcriptional activators hold enormous potential as therapeutic agents and as mechanistic probes. Previously we described an isoxazolidine bearing functional groups similar to natural transcriptional activators that up-regulates transcription 80-fold at 1 mu M in cell culture. In this study, we analyze analogs of this molecule to define key characteristics of small molecules that function as transcriptional activation domains in cells. Conformational rigidity is an important contributor to function as is an overall amphipathic substitution pattern. Using these criteria, we identified additional molecular scaffolds with excellent (similar to 60-fold) activity as transcriptional activation domains. These results point the way for the creation of new generations of small molecules with this function. (C) 2008 Elsevier Ltd. All rights reserved.