5-(2-氟苯基)-1,3,4-噁二唑-2(3H)-酮 | 1044766-09-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 5-(2-氟苯基)-1,3,4-噁二唑-2(3H)-酮
• 英文名称: 5-(2-fluorophenyl)-1,3,4-oxadiazol-2(3H)-one
• 英文别名: 5-(2-fluorophenyl)-3H-1,3,4-oxadiazol-2-one
• CAS: 1044766-09-7
• 化学式: C₈H₅FN₂O₂
• 分子量: 180.138
• InChiKey: GRLMQTZJXSLUBV-UHFFFAOYSA-N

物化性质

• 密度：
  1.49±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  50.7
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302

反应信息

• 作为反应物：
  描述：

  5-(2-氟苯基)-1,3,4-噁二唑-2(3H)-酮 、 丙酸 在 N-甲基咪唑 作用下， 以 乙腈 为溶剂， 反应 24.0h， 以76%的产率得到2-fluoro-N'-propionylbenzohydrazide
  参考文献：
  名称：

  掩蔽 N-酰基-N-异氰酸酯的研究：支持恶二唑酮作为封闭的 N-异氰酸酯前体。

  摘要：

  与作为常见结构单元的碳取代异氰酸酯相比，N-取代异氰酸酯仍然不发达，关于其 N-酰基衍生物（即酰胺基异氰酸酯）的报道极为罕见。在本文中，在从简单的实验室稳定前体开始合成氮杂三肽和乙内酰脲亚基的背景下研究了酰胺基异氰酸酯。一个关键发现是原位形成的酰氨基异氰酸酯环化产生恶二唑酮，并且在合适的反应条件下，该杂环是无痕封闭（掩蔽）N-异氰酸酯。使用有机碱作为催化剂并在加热时观察到恶二唑酮的形成，以及各种亲核试剂以中等至高产率提供所需的氮杂二肽或乙内酰脲。

  DOI：

  10.1002/chem.202102301
• 作为产物：
  描述：

  三光气 、 2-氟亚苯基肼 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以84%的产率得到5-(2-氟苯基)-1,3,4-噁二唑-2(3H)-酮
  参考文献：
  名称：

  5-Phenyl-1,3,4-oxadiazol-2(3H)-ones Are Potent Inhibitors of Notum Carboxylesterase Activity Identified by the Optimization of a Crystallographic Fragment Screening Hit

  摘要：

  Carboxylesterase Notum is a negative regulator of the Wnt signaling pathway. There is an emerging understanding of the role Notum plays in disease, supporting the need to discover new small-molecule inhibitors. A crystallographic X-ray fragment screen was performed, which identified fragment hit 1,2,3-triazole 7 as an attractive starting point for a structure-based drug design hit-to-lead program. Optimization of 7 identified oxadiazol-2-one 23dd as a preferred example with properties consistent with druglike chemical space. Screening 23dd in a cell-based TCF/LEF reporter gene assay restored the activation of Wnt signaling in the presence of Notum. Mouse pharmacokinetic studies with oral administration of 23dd demonstrated good plasma exposure and partial blood-brain barrier penetration. Significant progress was made in developing fragment hit 7 into lead 23dd (>600-fold increase in activity), making it suitable as a new chemical tool for exploring the role of Notum-mediated regulation of Wnt signaling.

  DOI：

  10.1021/acs.jmedchem.0c01391

文献信息

• [EN] COMBINATION PHARMACEUTICAL AGENTS AS RSV INHIBITORS<br/>[FR] AGENTS PHARMACEUTIQUES EN COMBINAISON EN TANT QU'INHIBITEURS DE RSV
  申请人：ENANTA PHARM INC

  公开号：WO2019067864A1

  公开（公告）日：2019-04-04

  The present invention relates to pharmaceutical agents administered to a subject either in combination or in series for the treatment of a Respiratory Syncytial Virus (RSV) infection, wherein treatment comprises administering a compound effective to inhibit the function of the RSV and an additional compound or combinations of compounds having anti-RSV activity.

  本发明涉及用于治疗呼吸道合胞病毒（RSV）感染的药物剂，该药物剂可以单独或连续给予受试者，治疗包括给予一种有效抑制RSV功能的化合物以及具有抗RSV活性的另一种化合物或化合物组合。
• [EN] BENZODIAZEPINE DERIVATIVES AS RSV INHIBITORS<br/>[FR] DÉRIVÉS BENZODIAZÉPINE UTILISÉS COMME INHIBITEURS DU VIRUS RESPIRATOIRE SYNCYTIAL (RSV)
  申请人：ENANTA PHARM INC

  公开号：WO2017015449A1

  公开（公告）日：2017-01-26

  The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit Respiratory Syncytial Virus (RSV). The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from RSV infection. The invention also relates to methods of treating an RSV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

  本发明公开了化合物的结构式（I），或其药学上可接受的盐、酯或前药：这些化合物抑制呼吸道合胞病毒（RSV）。本发明还涉及包含上述化合物的药物组合物，用于治疗患有RSV感染的受试者。该发明还涉及通过给予包含本发明化合物的药物组合物来治疗受试者的RSV感染的方法。
• Benzodiazepine derivatives as RSV inhibitors
  申请人：Enanta Pharmaceuticals, Inc.

  公开号：US10570153B2

  公开（公告）日：2020-02-25

  The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit Respiratory Syncytial Virus (RSV). The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from RSV infection. The invention also relates to methods of treating an RSV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

  本发明公开了式（I）化合物或其药学上可接受的盐、酯或原药： 其可抑制呼吸道合胞病毒（RSV）。本发明进一步涉及包含上述化合物的药物组合物，用于给受 RSV 感染的患者用药。本发明还涉及通过施用包含本发明化合物的药物组合物治疗受试者 RSV 感染的方法。
• Combination pharmaceutical agents as RSV inhibitors
  申请人：Enanta Pharmaceuticals, Inc.

  公开号：US10881666B2

  公开（公告）日：2021-01-05

  The present invention relates to pharmaceutical agents administered to a subject either in combination or in series for the treatment of a Respiratory Syncytial Virus (RSV) infection, wherein treatment comprises administering a compound effective to inhibit the function of the RSV and an additional compound or combinations of compounds having anti-RSV activity.

  本发明涉及向受试者联合或系列施用治疗呼吸道合胞病毒（RSV）感染的药剂，其中治疗包括施用一种有效抑制 RSV 功能的化合物和另外一种或多种具有抗 RSV 活性的化合物组合。
• BENZODIAZEPINE DERIVATIVES AS RSV INHIBITORS
  申请人：Enanta Pharmaceuticals, Inc.

  公开号：EP3324977A1

  公开（公告）日：2018-05-30