(2R,4S,5S)-5-azido-6-(3,5-difluoro-phenoxy)-2-methoxyhexane-1,4-diol | 1216934-94-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (2R,4S,5S)-5-azido-6-(3,5-difluoro-phenoxy)-2-methoxyhexane-1,4-diol
• 英文别名: (2R,4S,5S)-5-azido-6-(3,5-difluoro-phenoxy)-2-methoxy-hexane-1,4-diol；(2R,4S,5S)-5-azido-6-(3,5-difluorophenoxy)-2-methoxyhexane-1,4-diol
• CAS: 1216934-94-9
• 化学式: C₁₃H₁₇F₂N₃O₄
• 分子量: 317.292
• InChiKey: FYYHNWHXMYJIHN-AGIUHOORSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  73.3
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (2R,4S,5S)-5-azido-6-(3,5-difluoro-phenoxy)-2-methoxyhexane-1,4-diol 在 5% Pd(II)/C(eggshell) 、 氢气 作用下， 以 甲醇 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  P2′-truncated BACE-1 inhibitors with a novel hydroxethylene-like core

  摘要：

  Highly potent BACE-1 protease inhibitors derived from a novel hydroxyethylene-like core structure were recently developed by our group using X-ray crystal structure data and molecular modelling. In a continuation of this work guided by molecular modelling we have explored a truncated core motif where the P2' amide group is replaced by an ether linkage resulting in a set of alkoxy, aryloxy and alkylaryl groups, with the overall aim to reduce molecular weight and the number of amide bonds to increase permeability and bestow the inhibitors with drug-like features. The most potent of these inhibitors displayed a BACE-I IC50 value of 140 nM. The synthesis of these BACE-I inhibitors utilizes readily available starting materials, furnishing the target compounds in good overall yields. (C) 2009 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2009.10.041
• 作为产物：
  描述：

  5-azido-3,5-dideoxy-6-O-(3,5-difluorophenyl)-2-O-methyl-L-lyxo-hexofuranose 在 锂硼氢 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以95%的产率得到(2R,4S,5S)-5-azido-6-(3,5-difluoro-phenoxy)-2-methoxyhexane-1,4-diol
  参考文献：
  名称：

  P2′-truncated BACE-1 inhibitors with a novel hydroxethylene-like core

  摘要：

  Highly potent BACE-1 protease inhibitors derived from a novel hydroxyethylene-like core structure were recently developed by our group using X-ray crystal structure data and molecular modelling. In a continuation of this work guided by molecular modelling we have explored a truncated core motif where the P2' amide group is replaced by an ether linkage resulting in a set of alkoxy, aryloxy and alkylaryl groups, with the overall aim to reduce molecular weight and the number of amide bonds to increase permeability and bestow the inhibitors with drug-like features. The most potent of these inhibitors displayed a BACE-I IC50 value of 140 nM. The synthesis of these BACE-I inhibitors utilizes readily available starting materials, furnishing the target compounds in good overall yields. (C) 2009 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2009.10.041

文献信息

• [EN] ASPARTYL PROTEASE INHIBITORS<br/>[FR] INHIBITEURS D'ASPARTYL PROTÉASE
  申请人：MEDIVIR AB

  公开号：WO2010042030A1

  公开（公告）日：2010-04-15

  A compound of formula (I): N-oxides, addition salts, quaternary amines metal complexes stereochemically isomeric forms and metabolites thereof, wherein A is CR1 or N; D is H, C1-C6alkyl, C2-C6alkenyl, C2-C6alkynyl or Q is C2-C6alkenyl, C2-Cealkynyl, aryl or heterocyclyl; W is H, Ci-Cealkyl, C2-C6alkenyl, haloC1-C3alkyl, hydroxyC1-C3alkyl, C3-C6Cy cloalkyl, aryl or heterocyclyl; one of X' and X" is H or CH3, the other is C1-C3alkyl, F, OH, NRaRb, CF3 or N3; or X' and X" are both F; Y is a bond, CH2, NRa, O, CH2CH2, CH2NRa, CH2O or S(=O)r; Z is O, S(=O)r or NRa; the other variables are as defined in the specification. The compounds of the invention are inhibitors of BACE and are among other things useful for the treatment and/or prevention of conditions associated with BACE activity such as Alzheimer's disease.

  公式（I）的化合物为：N-氧化物、加合盐、季铵盐金属配合物立体化学异构体及其代谢物，其中A为CR1或N；D为H、C1-C6烷基、C2-C6烯基、C2-C6炔基或Q为C2-C6烯基、C2-C6炔基、芳基或杂环基；W为H、C1-C6烷基、C2-C6烯基、卤代C1-C3烷基、羟基C1-C3烷基、C3-C6环烷基、芳基或杂环基；X'和X"中的一个为H或CH3，另一个为C1-C3烷基、F、OH、NRaRb、CF3或N3；或X'和X"都是F；Y为键、CH2、NRa、O、 、 NRa、 O或S(=O)r；Z为O、S(=O)r或NRa；其他变量如规范中所定义。该发明的化合物是BACE的抑制剂，可用于治疗和/或预防与BACE活性相关的疾病，如阿尔茨海默病。