3a,4-dihydro-3H,6H-furo[3,4-c][1,2]oxazole | 1174320-72-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑啉类
• 英文名称: 3a,4-dihydro-3H,6H-furo[3,4-c][1,2]oxazole
• 英文别名: (+/-)-3a,4-dihydro-3H,6H-furo[3,4-c]isoxazole；3,3a,4,6-tetrahydrofuro[3,4-c][1,2]oxazole
• CAS: 1174320-72-9
• 化学式: C₅H₇NO₂
• 分子量: 113.116
• InChiKey: REKGJUBQEKCTDR-UHFFFAOYSA-N

物化性质

• 沸点：
  184.5±50.0 °C(Predicted)
• 密度：
  1.54±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  8
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  30.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3a,4-dihydro-3H,6H-furo[3,4-c][1,2]oxazole 在 正丁基锂 、 1-氯-N,N,2-三甲基丙烯胺 、 三氟化硼乙醚 、 溶剂黄146 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 、 甲苯 为溶剂， 反应 37.25h， 生成 rac-(4aS,7aS)-7a-(2,4-difluorophenyl)-4a,5,7,7a-tetrahydro-4H-furo[3,4-d][1,3]thiazin-2-amine
  参考文献：
  名称：

  Discovery of a Series of Efficient, Centrally Efficacious BACE1 Inhibitors through Structure-Based Drug Design

  摘要：

  The identification of centrally efficacious beta-secretase (BACE1) inhibitors for the treatment of Alzheimer's disease (AD) has historically been thwarted by an inability to maintain alignment of potency, brain availability, and desired absorption, distribution, metabolism, and excretion (ADME) properties. In this paper, we describe a series of truncated, fused thioamidines that are efficiently selective in garnering BACE1 activity without simultaneously inhibiting the closely related cathepsin D or negatively impacting brain penetration and ADME alignment, as exemplified by 36. Upon oral administration, these inhibitors exhibit robust brain availability and are efficacious in lowering central Amyloid beta (A beta) levels in mouse and dog. In addition, chronic treatment in aged PS1/APP mice effects a decrease in the number and size of A beta-derived plaques. Most importantly, evaluation of 36 in a 2-week exploratory toxicology study revealed no accumulation of autofluorescent material in retinal pigment epithelium or histology findings in the eye, issues observed with earlier BACE1 inhibitors.

  DOI：

  10.1021/jm501833t
• 作为产物：
  描述：

  2-(烯丙氧基)乙醛 在 sodium hypochlorite 、 硫酸羟胺 、 sodium acetate 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 21.0h， 生成 3a,4-dihydro-3H,6H-furo[3,4-c][1,2]oxazole
  参考文献：
  名称：

  [EN] FUSED AMINODIHYDROPYRIMIDONE DERIVATIVES
  [FR] DÉRIVÉS D’AMINODIHYDROPYRIMIDONE CONDENSÉE

  摘要：

  一种由通式（I）表示的化合物或其药用盐或其溶剂化物，其中环A是C6-14芳基或类似物，L是-NReCO-或类似物（其中Re是氢原子或类似物），环B是C6-14芳基或类似物，X是C1-3烷基或类似物，Y是单键或类似物，Z是C1-3烷基或类似物，R1、R2和Rx各自独立地是氢原子或类似物，R3、R4、R5和R6各自独立地是氢原子、卤素原子或类似物，具有Aβ产生抑制作用或BACE1抑制作用，并可用作预防或治疗由Aβ引起的以阿尔茨海默型痴呆为特征的神经退行性疾病的药物。

  公开号：

  WO2011009897A1

文献信息

• [EN] FUSED AMINODIHYDROPYRIMIDONE DERIVATIVES<br/>[FR] DÉRIVÉS D’AMINODIHYDROPYRIMIDONE CONDENSÉE
  申请人：EISAI R&D MAN CO LTD

  公开号：WO2011009897A1

  公开（公告）日：2011-01-27

  A compound represented by the general formula (I) or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein Ring A is a C6-14 aryl group or the like, L is -NReCO- or the like (wherein Re is a hydrogen atom or the like), Ring B is a C6-14 aryl group or the like, X is a C1-3 alkylene group or the like, Y is a single bond or the like, Z is a C1-3 alkylene group or the like, R1, R2 and Rx are each independently a hydrogen atom or the like, and R3, R4, R5 and R6 are independently a hydrogen atom, a halogen atom or the like, has an Aβ production inhibitory effect or a BACE1 inhibitory effect and is useful as a prophylactic or therapeutic agent for a neurodegenerative disease caused by Aβ and typified by Alzheimer-type dementia.

  一种由通式（I）表示的化合物或其药用盐或其溶剂化物，其中环A是C6-14芳基或类似物，L是-NReCO-或类似物（其中Re是氢原子或类似物），环B是C6-14芳基或类似物，X是C1-3烷基或类似物，Y是单键或类似物，Z是C1-3烷基或类似物，R1、R2和Rx各自独立地是氢原子或类似物，R3、R4、R5和R6各自独立地是氢原子、卤素原子或类似物，具有Aβ产生抑制作用或BACE1抑制作用，并可用作预防或治疗由Aβ引起的以阿尔茨海默型痴呆为特征的神经退行性疾病的药物。
• FUSED AMINODIHYDROPYRIMIDONE DERIVATIVES
  申请人：Castro Pineiro Jose Luis

  公开号：US20120202828A1

  公开（公告）日：2012-08-09

  A compound represented by the general formula (I) or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein Ring A is a C 6-14 aryl group or the like, L is —NR e CO— or the like (wherein R e is a hydrogen atom or the like), Ring B is a C 6-14 aryl group or the like, X is a C 1-3 alkylene group or the like, Y is a single bond or the like, Z is a C 1-3 alkylene group or the like, R 1 , R 2 and R x are each independently a hydrogen atom or the like, and R 3 , R 4 , R 5 and R 6 are independently a hydrogen atom, a halogen atom or the like, has an Aβ production inhibitory effect or a BACE1 inhibitory effect and is useful as a prophylactic or therapeutic agent for a neurodegenerative disease caused by Aβ and typified by Alzheimer-type dementia.

  化合物的一般式为（I）或其药学上可接受的盐或溶剂，其中环A为C6-14芳基或类似基团，L为-NReCO-或类似基团（其中Re为氢原子或类似物），环B为C6-14芳基或类似基团，X为C1-3烷基或类似基团，Y为单键或类似键，Z为C1-3烷基或类似基团，R1、R2和Rx各自独立地为氢原子或类似物，而R3、R4、R5和R6各自独立地为氢原子、卤素原子或类似物。该化合物具有Aβ产生抑制作用或BACE1抑制作用，并且可用作预防或治疗由Aβ引起的以阿尔茨海默型痴呆为代表的神经退行性疾病的药物。
• Fused aminodihydropyrimidone derivatives
  申请人：Castro Pineiro Jose Luis

  公开号：US09139594B2

  公开（公告）日：2015-09-22

  A compound represented by the general formula (I) or a pharmaceutically acceptable salt thereof or a solvate thereof, wherein Ring A is a C6-14 aryl group or the like, L is —NReCO— or the like (wherein Re is a hydrogen atom or the like), Ring B is a C6-14 aryl group or the like, X is a C1-3 alkylene group or the like, Y is a single bond or the like, Z is a C1-3 alkylene group or the like, R1, R2 and Rx are each independently a hydrogen atom or the like, and R3, R4, R5 and R6 are independently a hydrogen atom, a halogen atom or the like, has an Aβ production inhibitory effect or a BACE1 inhibitory effect and is useful as a prophylactic or therapeutic agent for a neurodegenerative disease caused by Aβ and typified by Alzheimer-type dementia.

  一种由普通公式（I）表示的化合物或其药学上可接受的盐或其溶剂，其中环A是C6-14芳基或类似物，L是—NReCO—或类似物（其中Re是氢原子或类似物），环B是C6-14芳基或类似物，X是C1-3烷基或类似物，Y是单键或类似物，Z是C1-3烷基或类似物，R1、R2和Rx各自独立地是氢原子或类似物，而R3、R4、R5和R6各自独立地是氢原子、卤素原子或类似物，具有Aβ制剂和BACE1抑制剂效应，并可用作预防或治疗由Aβ引起的神经退行性疾病，如阿尔茨海默病等的药物。
• Discovery of a Series of Efficient, Centrally Efficacious BACE1 Inhibitors through Structure-Based Drug Design
  作者：Christopher R. Butler、Michael A. Brodney、Elizabeth M. Beck、Gabriela Barreiro、Charles E. Nolan、Feng Pan、Felix Vajdos、Kevin Parris、Alison H. Varghese、Christopher J. Helal、Ricardo Lira、Shawn D. Doran、David R. Riddell、Leanne M. Buzon、Jason K. Dutra、Luis A. Martinez-Alsina、Kevin Ogilvie、John C. Murray、Joseph M. Young、Kevin Atchison、Ashley Robshaw、Cathleen Gonzales、Jinlong Wang、Yong Zhang、Brian T. O’Neill

  DOI：10.1021/jm501833t

  日期：2015.3.26

  The identification of centrally efficacious beta-secretase (BACE1) inhibitors for the treatment of Alzheimer's disease (AD) has historically been thwarted by an inability to maintain alignment of potency, brain availability, and desired absorption, distribution, metabolism, and excretion (ADME) properties. In this paper, we describe a series of truncated, fused thioamidines that are efficiently selective in garnering BACE1 activity without simultaneously inhibiting the closely related cathepsin D or negatively impacting brain penetration and ADME alignment, as exemplified by 36. Upon oral administration, these inhibitors exhibit robust brain availability and are efficacious in lowering central Amyloid beta (A beta) levels in mouse and dog. In addition, chronic treatment in aged PS1/APP mice effects a decrease in the number and size of A beta-derived plaques. Most importantly, evaluation of 36 in a 2-week exploratory toxicology study revealed no accumulation of autofluorescent material in retinal pigment epithelium or histology findings in the eye, issues observed with earlier BACE1 inhibitors.