匹莫迪韦 | 1629869-44-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 匹莫迪韦
• 中文别名: 吡莫地韦
• 英文名称: VX-787
• 英文别名: pimodivir；(2S,3S)-3-((5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl)amino)bicyclo[2.2.2]octane-2-carboxylic acid；(2S,3S)-3-((2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-yl)amino)bicyclo[2.2.2]octane-2-carboxylic acid；(2S,3S)-3-[[5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl]amino]bicyclo[2.2.2]octane-2-carboxylic acid
• CAS: 1629869-44-8
• 化学式: C₂₀H₁₉F₂N₅O₂
• 分子量: 399.4
• InChiKey: JGPXDNKSIXAZEQ-SBBZOCNPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  匹莫迪韦 在 盐酸 作用下， 以 2-甲基四氢呋喃 、 水 、 丙酮 为溶剂， 反应 9.0h， 生成 (2S,3S)-3-{[5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl]amino}bicyclo[2.2.2]octane-2-carboxylic acid hydrochloride
  参考文献：
  名称：

  [EN] ISOTHERMAL REACTIVE CRYSTALLISATION PROCESS FOR THE PREPARATION OF A CRYSTALLINE FORM OF PIMODIVIR HYDROCHLORIDE HEMIHYDRATE
  [FR] PROCÉDÉ DE CRISTALLISATION RÉACTIVE ISOTHERME POUR LA PRÉPARATION D'UNE FORME CRISTALLINE D'HÉMIHYDRATE DE CHLORHYDRATE DE PIMODIVIR

  摘要：

  The present invention relates to an isothermal reactive crystallisation procedure to obtain the HCl salt of (2S,3S)-3-{[5-fluoro-2-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-4-yl]amino}- bicyclo[2.2.2] octane-2-carboxylic acid hemihydrate in crystalline form using a solvent system comprising a mixture of water and one or more organic solvents.

  公开号：

  WO2019193428A1
• 作为产物：
  描述：

  meso-endo-tetrahydro-4,7-ethanoisobenzofuran-1,3-dione 在 盐酸 、 potassium phosphate 、 tris-(dibenzylideneacetone)dipalladium(0) 、 叠氮磷酸二苯酯 、 氢气 、 sodium methylate 、 三乙胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 四氢呋喃 、 2-甲基四氢呋喃 、 1,4-二氧六环 、 甲醇 、 氘代甲苯 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 20.0~115.0 ℃ 、275.8 kPa 条件下， 反应 183.17h， 生成 匹莫迪韦
  参考文献：
  名称：

  Discovery of a Novel, First-in-Class, Orally Bioavailable Azaindole Inhibitor (VX-787) of Influenza PB2

  摘要：

  In our effort to develop agents for the treatment of influenza, a phenotypic screening approach utilizing a cell protection assay identified a series of azaindole based inhibitors of the cap-snatching function of the PB2 subunit of the influenza A viral polymerase complex. Using a bDNA viral replication assay (Wagaman, P. C.; Leong, M. A.; Simmen, K. A. Development of a novel influenza A antiviral assay. J. Virol. Methods 2002, 105, 105-114) in cells as a direct measure of antiviral activity, we discovered a set of cyclohexyl carboxylic acid analogues, highlighted by VX-787 (2). Compound 2 shows strong potency versus multiple influenza A strains, including pandemic 2009 H1N1 and avian H5N1 flu strains, and shows an efficacy profile in a mouse influenza model even when treatment was administered 48 h after infection. Compound 2 represents a first-in-class, orally bioavailable, novel compound that offers potential for the treatment of both pandemic and seasonal influenza and has a distinct advantage over the current standard of care treatments including potency, efficacy, and extended treatment window.

  DOI：

  10.1021/jm5007275

文献信息

• A MEDICAMENT FOR TREATING INFLUENZA CHARACTERIZED BY COMBINING A CAP-DEPENDENT ENDONUCLEASE INHIBITOR AND AN ANTI-INFLUENZA DRUG
  申请人：Shionogi & Co., Ltd.

  公开号：US20200261481A1

  公开（公告）日：2020-08-20

  A medicament characterized in that (A) a compound represented by the formula (I): its pharmaceutically acceptable salt, or a solvate thereof, wherein P is hydrogen or a group to form a prodrug; A 1 is CR 1A R 1B , S or O; A 2 is CR 2A R 2B , S or O; A 3 is CR 3A R 3B , S or O; A 4 is each independently CR 4A R 4B , S or O; the number of hetero atoms among atoms constituting the ring which consists of A 1 , A 2 , A 3 , A 4 , nitrogen atom adjacent to A 1 and carbon atom adjacent to A 4 is 1 or 2; R 1A and R 1B are each independently hydrogen, halogen, alkyl or the like; R 2A and R 2B are each independently hydrogen, halogen, alkyl, or the like; R 3A and R 3B are each independently hydrogen, halogen, alkyl, or the like; R 4A are each independently hydrogen, halogen, alkyl, or the like; R 4B are each independently hydrogen, halogen, alkyl, or the like; R 3A and R 3B may be taken together with an adjacent carbon atom to form non-aromatic carbocycle or non-aromatic heterocycle; n is any integer of 1 to 2; and R 1 is or the like, is combined with (B) compound(s) having an anti-influenza activity, its pharmaceutically acceptable salt or a solvate thereof and/or an antibody having anti-influenza activity, is useful for treating or preventing influenza.

  一种药物，其特征在于（A）由以下式（I）表示的化合物： 其药学上可接受的盐，或其溶剂合物， 其中 P为氢或形成前药的基团; A 1 为CR 1A R 1B 、S或O; A 2 为CR 2A R 2B 、S或O; A 3 为CR 3A R 3B 、S或O; A 4 分别为独立的CR 4A R 4B 、S或O; 构成由A 1 、A 2 、A 3 、A 4 、邻接到A 1 的氮原子和邻接到A 4 的碳原子的环的原子中的杂原子数为1或2; R 1A 和R 1B 分别为独立的氢、卤素、烷基或类似物; R 2A 和R 2B 分别为独立的氢、卤素、烷基或类似物; R 3A 和R 3B 分别为独立的氢、卤素、烷基或类似物; R 4A 分别为独立的氢、卤素、烷基或类似物; R 4B 分别为独立的氢、卤素、烷基或类似物; R 3A 和R 3B 可以与相邻的碳原子结合形成非芳香碳环或非芳香杂环; n为1到2的任意整数; 和 R 1 为 或类似物， 与具有抗流感活性的（B）化合物，其药学上可接受的盐或其溶剂合物和/或具有抗流感活性的抗体结合，用于治疗或预防流感。
• INHIBITORS OF INFLUENZA VIRUSES REPLICATION
  申请人：Charifson Paul S.

  公开号：US20120171245A1

  公开（公告）日：2012-07-05

  Methods of inhibiting the replication of influenza viruses in a biological sample or patient, of reducing the amount of influenza viruses in a biological sample or patient, and of treating influenza in a patient, comprises administering to said biological sample or patient an effective amount of a compound represented by Structural Formula (I): or a pharmaceutically acceptable salt thereof, wherein the values of Structural Formula (IA) are as described herein. A compound is represented by Structural Formula (IA) or a pharmaceutically acceptable salt thereof, wherein the values of Structural Formula (IA) are as described herein. A pharmaceutical composition comprises an effective amount of such a compound or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant or vehicle.

  抑制生物样本或患者中流感病毒的复制、减少生物样本或患者中流感病毒量以及治疗患者流感的方法，包括向所述生物样本或患者施用有效量的由结构公式（I）表示的化合物： 或其药用可接受盐，其中结构公式（IA）的值如本文所述。由结构公式（IA）或其药用可接受盐表示的化合物，其中结构公式（IA）的值如本文所述。药物组合物包括有效量的上述化合物或其药用可接受盐，以及药用可接受载体、佐剂或车辆。
• AZA-PYRIDONE COMPOUNDS AND USES THEREOF
  申请人：Alios BioPharma, Inc.

  公开号：US20150072982A1

  公开（公告）日：2015-03-12

  Disclosed herein are aza-pyridone compounds, pharmaceutical compositions that include one or more aza-pyridone compounds, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an orthomyxovirus infection, with an aza-pyridone compounds. Examples of an orthomyxovirus viral infection include an influenza infection.

  本文揭示了氮杂吡啶酮化合物，包括一种或多种氮杂吡啶酮化合物的药物组合物，以及合成这些化合物的方法。本文还揭示了使用氮杂吡啶酮化合物改善和/或治疗疾病和/或病况的方法，包括流感病毒感染在内的正黏液病毒感染。
• [EN] IMPROVED PROCESS FOR PREPARING BORYL 7-AZAINDOLE COMPOUNDS<br/>[FR] PROCÉDÉ AMÉLIORÉ DE PRÉPARATION DE COMPOSÉS 7-AZAINDOLE BORYLE
  申请人：BOROPHARM INC

  公开号：WO2016191079A1

  公开（公告）日：2016-12-01

  The present disclosure relates to an improved process for the preparation of 3-boryl substituted azaindole compounds in high yields and high selectivity. Such azaindole compounds may be used as intermediates to form compounds with cytotoxic, anticancer, and antiviral activities.

  本公开涉及一种改进的工艺，用于高产率和高选择性地制备3-硼代取代的氮杂吲哚化合物。这种氮杂吲哚化合物可用作中间体，形成具有细胞毒性、抗癌和抗病毒活性的化合物。
• [EN] AZA-PYRIDONE COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS D'AZA-PYRIDONE ET LEURS UTILISATIONS
  申请人：ALIOS BIOPHARMA INC

  公开号：WO2016145103A1

  公开（公告）日：2016-09-15

  Disclosed herein are aza-pyridone compounds, pharmaceutical compositions that include one or more aza-pyridone compounds, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an orthomyxovirus infection, with an aza-pyridone compound. Examples of an orthomyxovirus viral infection include an influenza infection.

  本文披露了氮杂吡啶酮化合物、包含一种或多种氮杂吡啶酮化合物的药物组合物，以及合成这些化合物的方法。本文还披露了使用氮杂吡啶酮化合物改善和/或治疗疾病和/或病况的方法，包括对流感病毒感染等病况的治疗。其中，流感病毒感染是一种流感感染的例子。