(1R,2S,4R,7R,10S)-4-ethyl-12,15-difluoro-10-[4-(trifluoromethyl)phenyl]sulfonyl-17-oxa-5lambda6-thia-6-azatetracyclo[8.8.0.02,7.011,16]octadeca-11,13,15-triene 5,5-dioxide | 1104889-15-7

• 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: (1R,2S,4R,7R,10S)-4-ethyl-12,15-difluoro-10-[4-(trifluoromethyl)phenyl]sulfonyl-17-oxa-5lambda6-thia-6-azatetracyclo[8.8.0.02,7.011,16]octadeca-11,13,15-triene 5,5-dioxide
• 英文别名: (1R,2S,4R,7R,10S)-4-ethyl-12,15-difluoro-10-[4-(trifluoromethyl)phenyl]sulfonyl-17-oxa-5λ6-thia-6-azatetracyclo[8.8.0.02,7.011,16]octadeca-11,13,15-triene 5,5-dioxide
• CAS: 1104889-15-7
• 化学式: C₂₄H₂₄F₅NO₅S₂
• 分子量: 565.582
• InChiKey: AUQBDVFQGQPNMV-ZTJBWJTDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  37
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  (1R,2S,4R,7R,10S)-4-ethyl-12,15-difluoro-10-[4-(trifluoromethyl)phenyl]sulfonyl-17-oxa-5lambda6-thia-6-azatetracyclo[8.8.0.02,7.011,16]octadeca-11,13,15-triene 5,5-dioxide 在 Selectfluor 、 水 作用下， 以 乙腈 为溶剂， 反应 20.0h， 生成 (1R,2S,4R,7R,10S)-4-ethyl-15,15-difluoro-5,5-dioxo-10-[4-(trifluoromethyl)phenyl]sulfonyl-17-oxa-5lambda6-thia-6-azatetracyclo[8.8.0.02,7.011,16]octadeca-11(16),13-dien-12-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
• 作为产物：
  描述：

  在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 (1R,2S,4R,7R,10S)-4-ethyl-12,15-difluoro-10-[4-(trifluoromethyl)phenyl]sulfonyl-17-oxa-5lambda6-thia-6-azatetracyclo[8.8.0.02,7.011,16]octadeca-11,13,15-triene 5,5-dioxide
  参考文献：
  名称：

  [EN] BENZENESULFONYL-CHROMANE, THIOCHROMANE, TETRAHYDRONAPHTHALENE AND RELATED GAMMA SECRETASE INHIBITORS
  [FR] BENZÈNESULFONYLE-CHROMANE, THIOCHROMANE, TÉTRAHYDRONAPHTALÈNE ET INHIBITEURS DE GAMMA-SECRÉTASE ASSOCIÉS

  摘要：

  揭示了式(I)的新型γ-分泌酶抑制剂，或其药用可接受的盐、溶剂化合物或酯，其中L1、n、X、Ar、Y、Z、Q和Q1的定义如本文所述。还揭示了抑制γ-分泌酶的方法，治疗阿尔茨海默病的方法，治疗一种或多种神经退行性疾病的方法，以及使用式1.0化合物抑制淀粉样蛋白（例如淀粉样β蛋白）在神经组织（例如大脑）中的沉积的方法。

  公开号：

  WO2009011851A1

文献信息

• Tetracyclic sulfones as potent γ-secretase inhibitors: Synthesis and structure–activity relationship studies
  作者：T.K. Sasikumar、Duane A. Burnett、Theodros Asberom、Wen-Lian Wu、Chad Bennett、David Cole、Ruo Xu、William J. Greenlee、John Clader、Lili Zhang、Lynn Hyde

  DOI：10.1016/j.bmcl.2010.04.103

  日期：2010.6

  Complex tetracyclic sulfones were designed as gamma-secretase inhibitors and a stereoselective synthesis was achieved. gamma-Secretase activity was seen predominately in the (-) enantiomeric series. Compounds such as 2a and 2b showed remarkable in vitro and in vivo potency. (C) 2010 Elsevier Ltd. All rights reserved.
• BENZENESULFONYL-CHROMANE, THIOCHROMANE, TETRAHYDRONAPHTHALENE AND RELATED GAMMA SECRETASE INHIBITORS
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP2178882B1

  公开（公告）日：2013-04-17