(S)-3-phenyl-5-(pyrrolidin-2-yl)-1,2,4-oxadiazole | 871208-83-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (S)-3-phenyl-5-(pyrrolidin-2-yl)-1,2,4-oxadiazole
• 英文别名: 3-phenyl-5-[(2S)-pyrrolidin-2-yl]-1,2,4-oxadiazole
• CAS: 871208-83-2
• 化学式: C₁₂H₁₃N₃O
• mdl: MFCD08059301
• 分子量: 215.255
• InChiKey: RJBMVNYIOPXWKS-JTQLQIEISA-N

物化性质

• 沸点：
  378.7±52.0 °C(Predicted)
• 密度：
  1.173±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  51
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-3-phenyl-5-(pyrrolidin-2-yl)-1,2,4-oxadiazole 在 甲醇 、 4-二甲氨基吡啶 、 potassium carbonate 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 56.0h， 生成 2,2-dimethyl-4-oxo-4-((1R,3aS,5aR,5bR,7aR,9S,11aR,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((R)-2-(3-phenyl-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carbonyl)-1-(prop-1-en-2-yl)icosahydro-1H-cyclopenta[a]chrysen-9-yloxy)butanoic acid
  参考文献：
  名称：

  [EN] NOVEL BETULINIC ACID PROLINE DERIVATIVES AS HIV INHIBITORS
  [FR] NOUVEAUX DÉRIVÉS PROLINE DE L'ACIDE BÉTULINIQUE UTILISÉS COMME INHIBITEURS DU VIH

  摘要：

  这项发明涉及新型苦药酸衍生物和相关化合物，以及用于治疗病毒性疾病特别是HIV介导疾病的药物组合物。这些化合物在苦药酸结构的3位酯化，并且在17位通过连接基团W被取代，取代基是饱和的5-7元氮杂环。

  公开号：

  WO2014105926A1
• 作为产物：
  描述：

  苯甲酰胺肟 在 1-羟基苯并三唑 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.58h， 生成 (S)-3-phenyl-5-(pyrrolidin-2-yl)-1,2,4-oxadiazole
  参考文献：
  名称：

  一种用于治疗丙型肝炎病毒的有效、选择性和口服生物可利用的 HCV NS5A 抑制剂：(S)-1-((R)-2-(Cyclopropanecarboxamido)-2-phenylacetyl)-N-(4-phenylthiazol-2-yl )吡咯烷-2-甲酰胺

  摘要：

  从最初的铅 4-苯基噻唑18 开始，一种适度的 HCV 抑制剂 (EC 50 = 9440 nM)，一系列结构相关的噻唑衍生物已被确定为一种新型化学类别的有效和选择性 HCV NS5A 抑制剂。在化合物18的噻唑和吡咯烷环 ( 42 )之间引入甲酰胺基团导致活性显着增加 (EC 50 = 0.92 nM)。然而，42只在大鼠中显示出中等的药代动力学特性和有限的 18.7% 的口服生物利用度。噻唑环 4 位取代基和先导化合物42吡咯烷氮的进一步优化导致化合物57的鉴定，它是一种高效和选择性的 HCV NS5A 抑制剂 (EC 50 = 4.6 nM)，具有更高的治疗指数 (CC 50 /EC 50 > 10000)。药代动力学研究表明，化合物57在大鼠中口服给药后具有优异的口服暴露和 45% 的所需生物利用度。

  DOI：

  10.1021/acs.jmedchem.6b00962

文献信息

• Dpp-IV Inhibitors
  申请人：Edwards John Paul

  公开号：US20080015146A1

  公开（公告）日：2008-01-17

  The invention relates to compounds of formula (I) wherein Z, R 1-9 , n, A, X and R b have the meaning as cited in the description and the claims. Said compounds are useful as DPP-IV inhibitors. The invention also relates to the preparation of such compounds as well as the production and use thereof as medicament.

  本发明涉及公式(I)的化合物，其中Z、R1-9、n、A、X和Rb的含义如所述描述和权利要求中所述。所述化合物可用作DPP-IV抑制剂。本发明还涉及制备这些化合物的方法，以及作为药物的生产和使用。
• NOVEL BETULINIC ACID PROLINE DERIVATIVES AS HIV INHIBITORS
  申请人：HETERO RESEARCH FOUNDATION

  公开号：US20150337004A1

  公开（公告）日：2015-11-26

  The invention relates to novel betulinic acid derivatives and related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases.

  本发明涉及新型苦杏仁酸衍生物和相关化合物，以及用于治疗病毒性疾病，特别是HIV介导的疾病的药物组合物。
• Synthesis and structure-activity relationship study of pyrrolidine-oxadiazoles as anthelmintics against Haemonchus contortus
  作者：Banfeng Ruan、Yuezhou Zhang、Solomon Tadesse、Sarah Preston、Aya C. Taki、Abdul Jabbar、Andreas Hofmann、Yaqing Jiao、Jose Garcia-Bustos、Jitendra Harjani、Thuy Giang Le、Swapna Varghese、Silvia Teguh、Yiyue Xie、Jephthah Odiba、Min Hu、Robin B. Gasser、Jonathan Baell

  DOI：10.1016/j.ejmech.2020.112100

  日期：2020.3

  Parasitic roundworms (nematodes) are significant pathogens of humans and animals and cause substantive socioeconomic losses due to the diseases that they cause. The control of nematodes in livestock animals relies heavily on the use of anthelmintic drugs. However, their extensive use has led to a widespread problem of drug resistance in these worms. Thus, the discovery and development of novel chemical entities for the treatment of parasitic worms of humans and animals is needed. Herein, we describe our medicinal chemistry optimization efforts of a phenotypic hit against Haemonchus contortus based on a pyrrolidine-oxadiazole scaffold. This led to the identification of compounds with potent inhibitory activities (IC50 = 0.78-22.4 mu M) on the motility and development of parasitic stages of H. contortus, and which were found to be highly selective in a mammalian cell counter-screen. These compounds could be used as suitable chemical tools for drug target identification or as lead compounds for further optimization. (C) 2020 Elsevier Masson SAS. All rights reserved.
• The design of potent and selective inhibitors of DPP-4: Optimization of ADME properties by amide replacements
  作者：Sonja Nordhoff、Stephan Bulat、Silvia Cerezo-Gálvez、Oliver Hill、Barbara Hoffmann-Enger、Meritxell López-Canet、Claudia Rosenbaum、Christian Rummey、Meinolf Thiemann、Victor G. Matassa、Paul J. Edwards、Achim Feurer

  DOI：10.1016/j.bmcl.2009.09.078

  日期：2009.11

  For a series of beta-homophenylalanine based inhibitors of dipeptidyl peptidase IV ADME properties were improved by the incorporation of amide replacements. These efforts led to a novel series of potent and selective inhibitors of DPP-4 that exhibit an attractive pharmacokinetic profile and show excellent efficacy in an animal model of diabetes. (C) 2009 Elsevier Ltd. All rights reserved.
• NOVEL BETULINIC PROLINE IMIDAZOLE DERIVATIVES AS HIV INHIBITORS
  申请人：HETERO RESEARCH FOUNDATION

  公开号：US20170129916A1

  公开（公告）日：2017-05-11

  The invention relates to novel betulinic proline substituted derivatives, related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases.