(S)-N-(4-((3-cyano-1-isobutyl-1H-indol-5-yl)methyl)phenyl)pyrrolidine-2-carboxamide

• 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
• 英文名称: (S)-N-(4-((3-cyano-1-isobutyl-1H-indol-5-yl)methyl)phenyl)pyrrolidine-2-carboxamide
• 英文别名: (2S)-N-[4-[[3-cyano-1-(2-methylpropyl)indol-5-yl]methyl]phenyl]pyrrolidine-2-carboxamide
• 化学式: C₂₅H₂₈N₄O
• 分子量: 400.524
• InChiKey: KFEALFUIWDTBKJ-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  69.8
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  5-碘吲哚 在 四(三苯基膦)钯 、 palladium diacetate 、 caesium carbonate 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 139.17h， 生成 (S)-N-(4-((3-cyano-1-isobutyl-1H-indol-5-yl)methyl)phenyl)pyrrolidine-2-carboxamide
  参考文献：
  名称：

  Structure-Based Design of Potent and Selective Inhibitors of the Metabolic Kinase PFKFB3

  摘要：

  A weak screening hit with suboptimal physicochemical properties was optimized against PFKFB3 kinase using critical structure-guided insights. The resulting compounds demonstrated high selectivity over related PFKFB isoforms and modulation of the target in a cellular context. A selected example demonstrated exposure in animals following oral dosing. Examples from this series may serve as useful probes to understand the emerging biology of this metabolic target.

  DOI：

  10.1021/acs.jmedchem.5b00352

文献信息

• [EN] PFKFB3 INHIBITORS AND THEIR USES<br/>[FR] INHIBITEURS DE PFKFB3 ET LEURS UTILISATIONS
  申请人：GERO DISCOVERY LLC

  公开号：WO2020080979A1

  公开（公告）日：2020-04-23

  This disclosure relates to new phthalimide and isoindolinone derivatives and other PFKFB3 inhibitors for use in the treatment of diseases. The invention further relates to pharmaceutical compositions containing such PFKFB3 inhibitors, methods of preparation thereof, methods for their use as therapeutic agents, and methods of preparation of a medicament for use in therapy, as well as kits and other inventiions comprising such PFKFB3 inhibitors. These PFKFB3 inhibitors are useful for the treatment and prophylaxis of cancer, neurodegenerative diseases, autoimmune diseases, inflammatory disorders, multiple sclerosis, metabolic diseases, inhibition of angiogenesis and other diseases and conditions, where the modulation of PFKFB3 and/or PFKFB4 has beneficial effect as well as neuroprotection.

  这项披露涉及新的邻苯二甲酰亚胺和异吲哚酮衍生物以及其他PFKFB3抑制剂，用于治疗疾病。该发明还涉及含有此类PFKFB3抑制剂的药物组合物，其制备方法，作为治疗剂的使用方法，以及用于治疗的药物的制备方法，以及包含此类PFKFB3抑制剂的工具包和其他发明。这些PFKFB3抑制剂对于治疗和预防癌症、神经退行性疾病、自身免疫疾病、炎症性疾病、多发性硬化症、代谢性疾病、抑制血管生成以及其他疾病和情况具有用途，在这些情况下，PFKFB3和/或PFKFB4的调节具有益处，以及神经保护作用。
• Structure-Based Design of Potent and Selective Inhibitors of the Metabolic Kinase PFKFB3
  作者：Scott Boyd、Joanna L. Brookfield、Susan E. Critchlow、Iain A. Cumming、Nicola J. Curtis、Judit Debreczeni、Sébastien L. Degorce、Craig Donald、Nicola J. Evans、Sam Groombridge、Philip Hopcroft、Neil P. Jones、Jason G. Kettle、Scott Lamont、Hilary J. Lewis、Philip MacFaull、Sheila B. McLoughlin、Laurent J. M. Rigoreau、James M. Smith、Steve St-Gallay、Julie K. Stock、Andrew P. Turnbull、Edward R. Wheatley、Jon Winter、Jonathan Wingfield

  DOI：10.1021/acs.jmedchem.5b00352

  日期：2015.4.23

  A weak screening hit with suboptimal physicochemical properties was optimized against PFKFB3 kinase using critical structure-guided insights. The resulting compounds demonstrated high selectivity over related PFKFB isoforms and modulation of the target in a cellular context. A selected example demonstrated exposure in animals following oral dosing. Examples from this series may serve as useful probes to understand the emerging biology of this metabolic target.