(6aR,7S,10aS)-4,4-difluoro-7-(2-methylsulfonylethyl)-10a-[4-(trifluoromethyl)phenyl]sulfonyl-6,6a,7,8,9,10-hexahydrobenzo[c]chromen-1-one | 1417802-76-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (6aR,7S,10aS)-4,4-difluoro-7-(2-methylsulfonylethyl)-10a-[4-(trifluoromethyl)phenyl]sulfonyl-6,6a,7,8,9,10-hexahydrobenzo[c]chromen-1-one
• CAS: 1417802-76-6
• 化学式: C₂₃H₂₃F₅O₆S₂
• 分子量: 554.556
• InChiKey: RGRUYCOTOBGFGW-LFRPXUGBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  111
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  (6aR,7S,10aS)-1,4-difluoro-7-(2-methylsulfonylethyl)-10a-[4-(trifluoromethyl)phenyl]sulfonyl-6,6a,7,8,9,10-hexahydrobenzo[c]chromene 在 Selectfluor 、 水 作用下， 以 乙腈 为溶剂， 反应 20.0h， 生成 (6aR,7S,10aS)-4,4-difluoro-7-(2-methylsulfonylethyl)-10a-[4-(trifluoromethyl)phenyl]sulfonyl-6,6a,7,8,9,10-hexahydrobenzo[c]chromen-1-one
  参考文献：
  名称：

  A-ring modification of SCH 900229 and related chromene sulfone γ-secretase inhibitors

  摘要：

  Attempts to block metabolism by incorporating a 9-fluoro substituent at the A-ring of compound 1 (SCH 900229) using electrophilic Selectfluor (TM) led to an unexpected oxidation of the A-ring to give difluoroquinone analog 1a. Oxidation of other related chromene gamma-secretase inhibitors 2-8 resulted in similar difluoroquinone analogs 2a-8a, respectively. These quinone products exhibited comparable in vitro potency in a gamma-scretase membrane assay, but were several fold less potent in a cell-based assay in lowering A beta 40-42, compared to their parent compounds. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.11.054

文献信息

• A-ring modification of SCH 900229 and related chromene sulfone γ-secretase inhibitors
  作者：Wen-Lian Wu、Thavalakulamgara K. Sasikumar、Martin S. Domalski、Li Qiang、Duane A. Burnett、John Clader、William J. Greenlee、Tze-Ming Chan、Julie Lee、Lili Zhang

  DOI：10.1016/j.bmcl.2012.11.054

  日期：2013.2

  Attempts to block metabolism by incorporating a 9-fluoro substituent at the A-ring of compound 1 (SCH 900229) using electrophilic Selectfluor (TM) led to an unexpected oxidation of the A-ring to give difluoroquinone analog 1a. Oxidation of other related chromene gamma-secretase inhibitors 2-8 resulted in similar difluoroquinone analogs 2a-8a, respectively. These quinone products exhibited comparable in vitro potency in a gamma-scretase membrane assay, but were several fold less potent in a cell-based assay in lowering A beta 40-42, compared to their parent compounds. (c) 2012 Elsevier Ltd. All rights reserved.