2-[2-[(4S,4aS,10bS)-10b-(4-chlorophenyl)sulfonyl-7,10-difluoro-2,4,4a,5-tetrahydro-1H-pyrano[3,4-c]chromen-4-yl]ethylsulfanyl]acetonitrile | 1402428-42-5

• 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-[2-[(4S,4aS,10bS)-10b-(4-chlorophenyl)sulfonyl-7,10-difluoro-2,4,4a,5-tetrahydro-1H-pyrano[3,4-c]chromen-4-yl]ethylsulfanyl]acetonitrile
• CAS: 1402428-42-5
• 化学式: C₂₂H₂₀ClF₂NO₄S₂
• 分子量: 499.987
• InChiKey: TZXROYOZOMYIHU-BPXKWBHBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  110
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-[2-[(4S,4aS,10bS)-10b-(4-chlorophenyl)sulfonyl-7,10-difluoro-2,4,4a,5-tetrahydro-1H-pyrano[3,4-c]chromen-4-yl]ethylsulfanyl]acetonitrile 在 sulfur 、 间氯过氧苯甲酸 作用下， 生成 2-[2-[(4S,4aS,10bS)-10b-(4-chlorophenyl)sulfonyl-7,10-difluoro-2,4,4a,5-tetrahydro-1H-pyrano[3,4-c]chromen-4-yl]ethylsulfonylmethyl]-4,5-dihydro-1H-imidazole
  参考文献：
  名称：

  Design and synthesis of water soluble β-aminosulfone analogues of SCH 900229 as γ-secretase inhibitors

  摘要：

  In this paper we describe our strategy to improve the aqueous solubility of SCH 900229, a potent PS1-selective gamma-secretase inhibitor for the treatment of Alzheimer's disease. Incorporation of ionizable amino groups into the side chain terminal generates water soluble beta-aminosulfone analogues of SCH 900229 that maintain robust in vitro potency and in vivo efficacy. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.04.095
• 作为产物：
  描述：

  C₂₀H₁₉ClF₂O₅S 在 potassium methanolate 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 生成 2-[2-[(4S,4aS,10bS)-10b-(4-chlorophenyl)sulfonyl-7,10-difluoro-2,4,4a,5-tetrahydro-1H-pyrano[3,4-c]chromen-4-yl]ethylsulfanyl]acetonitrile
  参考文献：
  名称：

  Design and synthesis of water soluble β-aminosulfone analogues of SCH 900229 as γ-secretase inhibitors

  摘要：

  In this paper we describe our strategy to improve the aqueous solubility of SCH 900229, a potent PS1-selective gamma-secretase inhibitor for the treatment of Alzheimer's disease. Incorporation of ionizable amino groups into the side chain terminal generates water soluble beta-aminosulfone analogues of SCH 900229 that maintain robust in vitro potency and in vivo efficacy. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.04.095

文献信息

• [EN] GAMMA SECRETASE INHIBITORS<br/>[FR] INHIBITEURS DE GAMMA SÉCRÉTASE
  申请人：MERCK SHARP & DOHME

  公开号：WO2013036464A1

  公开（公告）日：2013-03-14

  Disclosed herein are compounds of Formula (I) (I) and pharmaceutically acceptable salts thereof, wherein each of the substituents is given the definition as set forth in the specification and claims. Also disclosed are pharmaceutical compositions containing the compound of Formula (I) and use of the compound in the treatment of neurodegenerative diseases or conditions such as Alzheimer's disease.

  本文披露了公式(I) (I)的化合物及其药学上可接受的盐，其中每个取代基的定义如规范和权利要求所述。还披露了含有公式(I)化合物的药物组合物以及使用该化合物治疗神经退行性疾病或病症，如阿尔茨海默病。
• GAMMA SECRETASE INHIBITORS
  申请人：Wu Wen-Lian

  公开号：US20140018342A1

  公开（公告）日：2014-01-16

  Disclosed herein are compounds of Formula (I) and pharmaceutically acceptable salts thereof, wherein each of the substituents is given the definition as set forth in the specification and claims. Also disclosed are pharmaceutical compositions containing the compound of Formula (I) and use of the compound in the treatment of neurodegenerative diseases or conditions such as Alzheimer's disease.
• US8933116B2
  申请人：——

  公开号：US8933116B2

  公开（公告）日：2015-01-13
• US9226927B2
  申请人：——

  公开号：US9226927B2

  公开（公告）日：2016-01-05
• Design and synthesis of water soluble β-aminosulfone analogues of SCH 900229 as γ-secretase inhibitors
  作者：Wen-Lian Wu、Duane A. Burnett、John Clader、William J. Greenlee、Qin Jiang、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.2016.04.095

  日期：2016.12

  In this paper we describe our strategy to improve the aqueous solubility of SCH 900229, a potent PS1-selective gamma-secretase inhibitor for the treatment of Alzheimer's disease. Incorporation of ionizable amino groups into the side chain terminal generates water soluble beta-aminosulfone analogues of SCH 900229 that maintain robust in vitro potency and in vivo efficacy. (C) 2016 Elsevier Ltd. All rights reserved.