(cis-4,7-dihydroisobenzofuran-3a,7a(1H,3H)-diyl)dimethanol | 57595-27-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氢呋喃
• 英文名称: (cis-4,7-dihydroisobenzofuran-3a,7a(1H,3H)-diyl)dimethanol
• 英文别名: ((3AR,7AS)-1,3,3A,4,7,7A-Hexahydroisobenzofuran-3A,7A-diyl)dimethanol；[(3aS,7aR)-7a-(hydroxymethyl)-1,3,4,7-tetrahydro-2-benzofuran-3a-yl]methanol
• CAS: 57595-27-4
• 化学式: C₁₀H₁₆O₃
• 分子量: 184.235
• InChiKey: ORPPPJDJZMSFHZ-AOOOYVTPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  49.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (cis-4,7-dihydroisobenzofuran-3a,7a(1H,3H)-diyl)dimethanol 在 盐酸 、 titanium(IV) tetraethanolate 、 sodium chlorite 、 sodium dihydrogenphosphate dihydrate 、 2-甲基-2-丁烯 、 1-氯-N,N,2-三甲基丙烯胺 、 dimethyl sulfide borane 、 叠氮磷酸二苯酯 、 palladium 10% on activated carbon 、 氢气 、 sodium hydride 、 N,N-二异丙基乙胺 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 二氯甲烷 、 乙酸乙酯 、 甲苯 、 mineral oil 、 叔丁醇 为溶剂， 110.0 ℃ 、515.03 kPa 条件下， 反应 133.67h， 生成 N-((4aRS,8aSR)-6-amino-5,6,7,8-tetrahydro-4H-4a,8a-(methanooxymethano)benzo[d][1,3]thiazin-2-yl)benzamide
  参考文献：
  名称：

  Preparation and biological evaluation of conformationally constrained BACE1 inhibitors

  摘要：

  The BACE1 enzyme is a key target for Alzheimer's disease. During our BACE1 research efforts, fragment screening revealed that bicyclic thiazine 3 had low millimolar activity against BACE1. Analysis of the co-crystal structure of 3 suggested that potency could be increased through extension toward the S3 pocket and through conformational constraint of the thiazine core. Pursuit of S3-binding groups produced low micromolar inhibitor 6, which informed the S3-design for constrained analogs 7 and 8, themselves prepared via independent, multi-step synthetic routes. Biological characterization of BACE inhibitors 6-8 is described. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.04.062
• 作为产物：
  描述：

  cis-1,6-Bis-(chloroformyl)-8-oxybicyclo<4.3.0>non-3-en 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以92%的产率得到(cis-4,7-dihydroisobenzofuran-3a,7a(1H,3H)-diyl)dimethanol
  参考文献：
  名称：

  Preparation and biological evaluation of conformationally constrained BACE1 inhibitors

  摘要：

  The BACE1 enzyme is a key target for Alzheimer's disease. During our BACE1 research efforts, fragment screening revealed that bicyclic thiazine 3 had low millimolar activity against BACE1. Analysis of the co-crystal structure of 3 suggested that potency could be increased through extension toward the S3 pocket and through conformational constraint of the thiazine core. Pursuit of S3-binding groups produced low micromolar inhibitor 6, which informed the S3-design for constrained analogs 7 and 8, themselves prepared via independent, multi-step synthetic routes. Biological characterization of BACE inhibitors 6-8 is described. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.04.062