2-[(4S,4aS,10bS)-10b-(3,4-difluorophenyl)sulfonyl-7,10-difluoro-2,4,4a,5-tetrahydro-1H-pyrano[3,4-c]chromen-4-yl]ethanol | 1100361-92-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 2-[(4S,4aS,10bS)-10b-(3,4-difluorophenyl)sulfonyl-7,10-difluoro-2,4,4a,5-tetrahydro-1H-pyrano[3,4-c]chromen-4-yl]ethanol
• CAS: 1100361-92-9
• 化学式: C₂₀H₁₈F₄O₅S
• 分子量: 446.42
• InChiKey: MRLGPDICMIBZLS-JTBRQZTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  81.2
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-[(4S,4aS,10bS)-10b-(3,4-difluorophenyl)sulfonyl-7,10-difluoro-2,4,4a,5-tetrahydro-1H-pyrano[3,4-c]chromen-4-yl]ethanol 在 四丁基碘化铵 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 (4S,4aS,10bS)-10b-(3,4-difluorophenyl)sulfonyl-7,10-difluoro-4-(2-methylsulfonylethyl)-2,4,4a,5-tetrahydro-1H-pyrano[3,4-c]chromene
  参考文献：
  名称：

  Structure activity relationship studies of tricyclic bispyran sulfone γ-secretase inhibitors

  摘要：

  An investigation is detailed of the structure activity relationships (SAR) of two sulfone side chains of compound (-)-1a (SCH 900229), a potent, PS1-selective gamma-secretase inhibitor and clinical candidate for the treatment of Alzheimer's disease. Specifically, 4-CF3 and 4-Br substituted arylsulfone analogs, (-)-1b and (-)-1c, are equipotent to compound (-)-1a. On the right hand side chain, linker size and terminal substituents of the pendant sulfone group are also investigated. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.11.047
• 作为产物：
  描述：

  在 三氟甲磺酸三甲基硅酯 、 三氟化硼乙醚 、 potassium tert-butylate 、 戴斯-马丁氧化剂 、 臭氧 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 2-[(4S,4aS,10bS)-10b-(3,4-difluorophenyl)sulfonyl-7,10-difluoro-2,4,4a,5-tetrahydro-1H-pyrano[3,4-c]chromen-4-yl]ethanol
  参考文献：
  名称：

  Structure activity relationship studies of tricyclic bispyran sulfone γ-secretase inhibitors

  摘要：

  An investigation is detailed of the structure activity relationships (SAR) of two sulfone side chains of compound (-)-1a (SCH 900229), a potent, PS1-selective gamma-secretase inhibitor and clinical candidate for the treatment of Alzheimer's disease. Specifically, 4-CF3 and 4-Br substituted arylsulfone analogs, (-)-1b and (-)-1c, are equipotent to compound (-)-1a. On the right hand side chain, linker size and terminal substituents of the pendant sulfone group are also investigated. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.11.047

文献信息

• TETRAHYDROPYRANOCHROMENE GAMMA SECRETASE INHIBITORS
  申请人：Wu Wen-Lian

  公开号：US20110236400A1

  公开（公告）日：2011-09-29

  Disclosed are novel gamma secretase inhibitors of the formula. Also disclosed are methods of inhibiting gamma-secretase, methods of treating neurodegenerative diseases, and methods of treating Alzheimer's Disease. Also disclosed are processes for preparing alkenes in one reaction step using a mixture of an aldehyde (or ketone) and an alkyl substituted with two electron withdrawing groups, and reacting the mixture with: (a) a sulfonyl halide (e.g., a sulfonyl chloride) and a basic tertiary amine, or, (b) a sulfonyl anhydride and a basic amine, or (c) an aryl-C(O)-halide and a basic tertiary amine, or (d) an aryl-C(O)—O—C(O)-aryl and a basic tertiary amine, or (e) an heteroaryl-C(O)-halide and a basic tertiary amine, or (f) a heteroaryl-C(O)—O—C(O)-heteroaryl and a basic tertiary amine.

  本发明涉及一种新型伽马分泌酶抑制剂的公开。还公开了抑制伽马分泌酶的方法、治疗神经退行性疾病的方法和治疗阿尔茨海默病的方法。还公开了一种使用醛（或酮）和烷基取代的两个电子提取基团的混合物，在一步反应中制备烯烃的方法，并将该混合物与：（a）磺酰卤化物（例如磺酰氯）和碱性三级胺反应，或（b）磺酰酐和碱性胺反应，或（c）芳基-C（O）-卤和碱性三级胺反应，或（d）芳基-C（O）-O-C（O）-芳基和碱性三级胺反应，或（e）杂环芳基-C（O）-卤和碱性三级胺反应，或（f）杂环芳基-C（O）-O-C（O）-杂环芳基和碱性三级胺反应。
• [EN] TETRAHYDROPYRANOCHROMENE GAMMA SECRETASE INHIBITORS<br/>[FR] INHIBITEURS DE LA TÉTRAHYDROPYRANOCHROMÈNE GAMMA SECRÉTASE
  申请人：SCHERING CORP

  公开号：WO2009008980A3

  公开（公告）日：2009-03-19
• US8664411B2
  申请人：——

  公开号：US8664411B2

  公开（公告）日：2014-03-04
• Structure activity relationship studies of tricyclic bispyran sulfone γ-secretase inhibitors
  作者：Wen-Lian Wu、Theodros Asberom、Thomas Bara、Chad Bennett、Duane A. Burnett、John Clader、Martin Domalski、William J. Greenlee、Hubert Josien、Mark McBriar、Murali Rajagopalan、Monica Vicarel、Ruo Xu、Lynn A. Hyde、Robert A. Del Vecchio、Mary E. Cohen-Williams、Lixin Song、Julie Lee、Giuseppe Terracina、Qi Zhang、Amin Nomeir、Eric M. Parker、Lili Zhang

  DOI：10.1016/j.bmcl.2012.11.047

  日期：2013.2

  An investigation is detailed of the structure activity relationships (SAR) of two sulfone side chains of compound (-)-1a (SCH 900229), a potent, PS1-selective gamma-secretase inhibitor and clinical candidate for the treatment of Alzheimer's disease. Specifically, 4-CF3 and 4-Br substituted arylsulfone analogs, (-)-1b and (-)-1c, are equipotent to compound (-)-1a. On the right hand side chain, linker size and terminal substituents of the pendant sulfone group are also investigated. (c) 2012 Elsevier Ltd. All rights reserved.