ethyl cis-3a,4,6,6a-tetrahydrofuro[3,4-d]isoxazole-3-carboxylate

• 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: ethyl cis-3a,4,6,6a-tetrahydrofuro[3,4-d]isoxazole-3-carboxylate
• 英文别名: (3aS,6aS)-rac-3a,4,6,6a-tetrahydro-furo[3,4-d]isoxazole-3-carboxylic acid ethyl ester；ethyl (3aR,6aR)-3a,4,6,6a-tetrahydrofuro[3,4-d][1,2]oxazole-3-carboxylate
• 化学式: C₈H₁₁NO₄
• 分子量: 185.18
• InChiKey: MJSOAHCFPLUFEP-RITPCOANSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.05
• 重原子数：
  13.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  57.12
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  ethyl cis-3a,4,6,6a-tetrahydrofuro[3,4-d]isoxazole-3-carboxylate 在 吡啶 、 sodium tetrahydroborate 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 Butyric acid (3aR,6aR)-1-(3a,4,6,6a-tetrahydro-furo[3,4-d]isoxazol-3-yl)methyl ester
  参考文献：
  名称：

  Nitrile oxides in medicinal chemistry. 6. Enzymatic resolution of a set of bicyclic Δ2-isoxazolines

  摘要：

  Chymotrypsin selectively catalyzed the hydrolysis of a series of 3-ethoxycarbonyl-Delta(2)-isoxazolines 1-4, whereas lipase from Pseudomonas cepacia (lipase PS) was remarkably selective in hydrolysing the corresponding 3-hydroxymethyl-Delta(2)-isoxazoline butyrates (5-8). The enantio-preference of chymotrypsin for the first set of compounds is the same as that observed for the lipase PS-cataiyzed hydrolysis of the other series of substrates. The hydrolytic activity of lipase PS for compounds 5-8 was considerably higher than that shown by chymotrypsin for substrates 1-4. (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/0957-4166(96)00075-4
• 作为产物：
  描述：

  2,5-二氢呋喃 、 氯代肟基乙酸乙酯 在 碳酸氢钠 作用下， 以 乙酸乙酯 为溶剂， 以84 %的产率得到ethyl cis-3a,4,6,6a-tetrahydrofuro[3,4-d]isoxazole-3-carboxylate
  参考文献：
  名称：

  螺环和稠合异恶唑啉砌块的合成

  摘要：

  公开了一种通过功能化的氯肟和环烯烃的 1,3-偶极环加成合成稠合和螺环sp 3富集异恶唑啉结构单元的可扩展且有效的方法。目标化合物以多克规模制备，并揭示了它们进一步功能化的潜力。

  DOI：

  10.1002/ejoc.202300282

文献信息

• N-[3-(5-AMINO-3,3A,7,7A-TETRAHYDRO-1H-2,4-DIOXA-6-AZA-INDEN-7-YL)-PHENYL]-AMIDES AS BACE1 AND/OR BACE2 INHIBITORS
  申请人：Hilpert Hans

  公开号：US20120202803A1

  公开（公告）日：2012-08-09

  The present invention relates to N-[3-(5-Amino-3,3a,7,7a-tetrahydro-1H-2,4-dioxa-6-aza-inden-7-yl)-phenyl]-amides of formula I having BACE1 and/or BACE2 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease and type 2 diabetes.

  本发明涉及具有BACE1和/或BACE2抑制活性的公式I的N-[3-(5-氨基-3,3a,7,7a-四氢-1H-2,4-二氧杂-6-氮杂-茚-7-基)-苯基]-酰胺，其制备方法，含有它们的药物组合物以及它们作为治疗活性物质的用途。本发明的活性化合物在治疗和/或预防治疗例如阿尔茨海默病和2型糖尿病方面是有用的。
• [EN] N-[3-(5-AMINO-3,3A,7,7A-TETRAHYDRO-1H-2,4-DIOXA-6-AZA-INDEN-7-YL)-PHENYL]-AMIDES AS BACE1 AND/OR BACE2 INHIBITORS<br/>[FR] N-[3-(5-AMINO-3,3A,7,7A-TÉTRAHYDRO-1H-2,4-DIOXA-6-AZAINDÉN-7-YL)-PHÉNYL] AMIDES EN TANT QU'INHIBITEURS DE BACE1 ET/OU DE BACE2
  申请人：HOFFMANN LA ROCHE

  公开号：WO2012107371A1

  公开（公告）日：2012-08-16

  The present invention relates to N-[3-(5-Amino-3,3a,7,7a-tetrahydro-1H-2,4-dioxa-6-aza-inden-7-yl)-phenyl]-amides of formula (I) having BACE1 and/or BACE2 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease and type 2 diabetes.

  本发明涉及具有BACE1和/或BACE2抑制活性的式(I)的N-[3-(5-氨基-3,3a,7,7a-四氢-1H-2,4-二氧杂-6-氮杂-茚-7-基)-苯基]-酰胺，其制备方法，含有它们的药物组合物以及它们作为治疗活性物质的用途。本发明的活性化合物在治疗和/或预防阿尔茨海默病和2型糖尿病等疾病中具有用途。
• Nitrile oxides in medicinal chemistry. 6. Enzymatic resolution of a set of bicyclic Δ2-isoxazolines
  作者：Marco De Amici、Carlo De Micheli、Giacomo Carrea、Sergio Riva

  DOI：10.1016/0957-4166(96)00075-4

  日期：1996.3

  Chymotrypsin selectively catalyzed the hydrolysis of a series of 3-ethoxycarbonyl-Delta(2)-isoxazolines 1-4, whereas lipase from Pseudomonas cepacia (lipase PS) was remarkably selective in hydrolysing the corresponding 3-hydroxymethyl-Delta(2)-isoxazoline butyrates (5-8). The enantio-preference of chymotrypsin for the first set of compounds is the same as that observed for the lipase PS-cataiyzed hydrolysis of the other series of substrates. The hydrolytic activity of lipase PS for compounds 5-8 was considerably higher than that shown by chymotrypsin for substrates 1-4. (C) 1996 Elsevier Science Ltd
• Synthesis of Spirocyclic and Fused Isoxazoline Building Blocks
  作者：Bohdan A. Chalyk、Vitalii V. Izhyk、Kyrylo Danyleiko、Bohdan Sosunovych、Bohdan V. Vashchenko、Oleksandr Zginnyk、Violetta Olshanska、Peter Teodorovic、Angelina V. Biitseva、Dmitriy M. Volochnyuk、Oleksandr O. Grygorenko

  DOI：10.1002/ejoc.202300282

  日期：2023.6.6

  A scalable and efficient approach to the synthesis of fused and spirocyclic sp3-enriched isoxazoline building blocks via the 1,3-dipolar cycloaddition of functionalized chloroximes and cyclic alkenes is disclosed. The target compounds are prepared on a multigram scale, and their potential for further functionalization is revealed.

  公开了一种通过功能化的氯肟和环烯烃的 1,3-偶极环加成合成稠合和螺环sp 3富集异恶唑啉结构单元的可扩展且有效的方法。目标化合物以多克规模制备，并揭示了它们进一步功能化的潜力。