(3R,5S,7as)-(3,5-bis(4-fluorophenyl)tetrahydro-1H-oxazolo[3,4-c]oxazol-7a-yl)methanol

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (3R,5S,7as)-(3,5-bis(4-fluorophenyl)tetrahydro-1H-oxazolo[3,4-c]oxazol-7a-yl)methanol
• 英文别名: 2,8-di-(p-fluorophenyl)-5-hydroxymethyl-1-aza-3,7-dioxabicyclo[3.3.0]octane；CCDC 706431
• 化学式: C₁₈H₁₇F₂NO₃
• 分子量: 333.335
• InChiKey: AEZQGSQEXPUADE-BCDXTJNWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.76
• 重原子数：
  24.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  41.93
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (3R,5S,7as)-(3,5-bis(4-fluorophenyl)tetrahydro-1H-oxazolo[3,4-c]oxazol-7a-yl)methanol 在 氨 、 对甲苯磺酸 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 甲醇 、 甲苯 、 苯 为溶剂， 反应 18.0h， 生成 2,8-di-(4-fluorophenyl)-5-hydroxymethyl-1-aza-3-oxa-7-thiabicyclo[3.3.0]octane
  参考文献：
  名称：

  Synthesis and Ring-Chain-Ring Tautomerism of Bisoxazolidines, Thiazolidinyloxazolidines, and Spirothiazolidines

  摘要：

  The synthesis of fused heterocycles such as thiazolidinyl-oxazolidine 3 is described starting from Tris center dot HCl. The mercaptomethyl bisoxazolidine 8 was found to convert to the corresponding thiazolidinyloxazolidine 3 and the spiro-heterocycle 4 by a ring-chain-ring tautomerism, depending on the electronic nature of the ring substituents as well as the reaction conditions. This equilibration pathway is absent in the hydroxymethyl bisoxazolidines 2. Computational studies confirm that both kinetic and thermodynamic control features play a role in the product distribution.

  DOI：

  10.1021/jo2008498
• 作为产物：
  描述：

  三羟甲基氨基甲烷盐酸盐 、 对氟苯甲醛 在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 12.0h， 以34%的产率得到(3R,5S,7as)-(3,5-bis(4-fluorophenyl)tetrahydro-1H-oxazolo[3,4-c]oxazol-7a-yl)methanol
  参考文献：
  名称：

  Synthesis and Ring-Chain-Ring Tautomerism of Bisoxazolidines, Thiazolidinyloxazolidines, and Spirothiazolidines

  摘要：

  The synthesis of fused heterocycles such as thiazolidinyl-oxazolidine 3 is described starting from Tris center dot HCl. The mercaptomethyl bisoxazolidine 8 was found to convert to the corresponding thiazolidinyloxazolidine 3 and the spiro-heterocycle 4 by a ring-chain-ring tautomerism, depending on the electronic nature of the ring substituents as well as the reaction conditions. This equilibration pathway is absent in the hydroxymethyl bisoxazolidines 2. Computational studies confirm that both kinetic and thermodynamic control features play a role in the product distribution.

  DOI：

  10.1021/jo2008498

文献信息

• Neuroprotective agents
  申请人：Michaelis Louise Mary

  公开号：US20070099971A1

  公开（公告）日：2007-05-03

  Novel stereoisomers of GS-164 are provided. The compounds, such as (3R,5S,7as)-(3,5-bis(4-fluorophenyl)tetrahydro-1H-oxazolo[3,4-c]oxazol-7a-yl)methanol (TH-237A) and (3R,5S,7as)-(3,5-bis(4-fluorophenyl)tetrahydro-1H-oxazolo[3,4-c]oxazol-7a-yl)methanol (TH-242A) exhibit neuroprotective effects via a mechanism that does not involve microtubule stabilization.

  提供了GS-164的新立体异构体。这些化合物，例如(3R,5S,7as)-(3,5-双(4-氟苯基)四氢-1H-噁唑并[3,4-c]噁唑-7a-基)甲醇(TH-237A)和(3R,5S,7as)-(3,5-双(4-氟苯基)四氢-1H-噁唑并[3,4-c]噁唑-7a-基)甲醇(TH-242A)，通过一种不涉及微管稳定的机制表现出神经保护作用。
• PRODRUGS OF (3,5-BIS(4-FLUOROPHENYL)TETRAHYDRO-1H-OXAZOLO[3,4-C]OXAZOL-7A-YL)METHANOL AND DERIVATIVES THEREOF
  申请人：Rajewski Roger A.

  公开号：US20100056592A1

  公开（公告）日：2010-03-04

  A prodrug that has a prodrug moiety that degrades into a compound having the general Formula I with R3 being an alcoholic moiety can be useful in therapies for neurodegenerative diseases as well as cancer. Accordingly, the prodrug compounds can have a structure of Formula I, analogs thereof, derivatives thereof, or salts thereof, wherein: A and B are sulfur or oxygen; R1 and R2, in para, meta, or ortho position, are independently halogen, alkyl, alkoxy, haloalkyl, where R1 and R2 independently are straight chain, branched, substituted or unsubstituted; and R3 is a prodrug moiety. As examples, the prodrug can have a structure of any of Formulas I-V, which as shown in the specification.

  具有可降解为具有一般式I的化合物的前药基团的前药可以用于神经退行性疾病以及癌症的治疗。因此，前药化合物可以具有I式、其类似物、衍生物或盐的结构，其中：A和B是硫或氧；R1和R2在对、间或邻位独立地是卤素、烷基、烷氧基、卤代烷基，其中R1和R2独立地是直链、支链、取代或未取代的；而R3是前药基团。例如，前药可以具有任何I-V式的结构，如规范中所示。
• (3<i>R</i>,5<i>S</i>,7a<i>s</i>)-(3,5-Bis(4-fluorophenyl)tetrahydro-1<i>H</i>-oxazolo[3,4-<i>c</i>]oxazol-7a-yl)methanol, a Novel Neuroprotective Agent
  作者：Kelly E. Desino、Sabah Ansar、Gunda I. Georg、Richard H. Himes、Mary Lou Michaelis、Douglas R. Powell、Emily A. Reiff、Hanumaiah Telikepalli、Kenneth L. Audus

  DOI：10.1021/jm900254k

  日期：2009.12.10

  Compounds that interact with microtubules, such as paclitaxel, have been shown to possess protective properties against beta-amyloid (A beta) induced neurodegeneration associated with Alzheimer's disease. In this work, the novel agent (3R,5S,7as)-(3,5-bis(4-fluorophenyl)tetrahydro-1H-oxazolo[3,4-c]oxazol-7a-yl)methanol was investigated for effectiveness in protecting neurons against several toxic stimuli and its interaction with the microtubule network. Exposure of neuronal cultures to A beta peptide in the presence of 5 nM (3R,5S,7as)-(3,5-bis(4-fluorophenyl)tetrahydro-1H-oxazolo[3,4-c]oxazol-7a-yl)methanol resulted in a 50% increase in survival, Neuronal cultures treated with other toxic stimuli such as staurosporine, thapsigargin, paraquat, and H2O2 showed significantly enhanced survival in the presence of (3R,5S,7as)-(3,5-bis(4-fluorophenyl)tetrahydro-1H-oxazolo[3,4-c]oxazol-7a-yl)methanol. Microtubule binding and tubulin assembly studies revealed differences compared to paclitaxel but confirmed the interaction of (3 R, 5 S, 7as)-(3,5-bis(4-fluorophenyl)tetrahydro-1H-oxazolo[3,4-c]oxazol-7a-yl)methanol with microtubules. Furthermore, in vitro studies using bovine brain microvessel endothelial cells experiments suggest that (3R,5S,7as)-(3,5-bis(4-fluorophenyl)tetrahydro-1H-oxazolo[3,4-c]oxazol-7a-yl)methanol can readily cross the blood-brain barrier in a passive manner.
• US7598282B2
  申请人：——

  公开号：US7598282B2

  公开（公告）日：2009-10-06
• US8318787B2
  申请人：——

  公开号：US8318787B2

  公开（公告）日：2012-11-27