N-(5-(2,3-dihydrobenzo[b][1,4]dioxine-5-carboxamido)-2-methylphenyl)-2-(2-(pyrrolidin-1-yl)ethoxy)quinoline-6-carboxamide

• 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: N-(5-(2,3-dihydrobenzo[b][1,4]dioxine-5-carboxamido)-2-methylphenyl)-2-(2-(pyrrolidin-1-yl)ethoxy)quinoline-6-carboxamide
• 英文别名: CCT273166；N-[5-(2,3-dihydro-1,4-benzodioxine-5-carbonylamino)-2-methylphenyl]-2-(2-pyrrolidin-1-ylethoxy)quinoline-6-carboxamide
• 化学式: C₃₂H₃₂N₄O₅
• 分子量: 552.63
• InChiKey: BQURSSYYGUBULA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  41
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  N-(2-羟乙基)-吡咯烷 在 正丁基锂 、 sodium hydride 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 正己烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 5.51h， 生成 N-(5-(2,3-dihydrobenzo[b][1,4]dioxine-5-carboxamido)-2-methylphenyl)-2-(2-(pyrrolidin-1-yl)ethoxy)quinoline-6-carboxamide
  参考文献：
  名称：

  Discovery of a Chemical Probe Bisamide (CCT251236): An Orally Bioavailable Efficacious Pirin Ligand from a Heat Shock Transcription Factor 1 (HSF1) Phenotypic Screen

  摘要：

  Phenotypic screens, which focus on measuring and quantifying discrete cellular changes rather than affinity for individual recombinant proteins, have recently attracted renewed interest as an efficient strategy for drug discovery. In this article, we describe the discovery of a new chemical probe, bisamide (CCT251236), identified using an unbiased phenotypic screen to detect inhibitors of the HSF1 stress pathway. The chemical probe is orally bioavailable and displays efficacy in a human ovarian carcinoma xenograft model. By developing cell:based SAP. and using chemical proteomics, we identified pirin as a high affinity molecular target, which was confirmed by SPR and crystallography.

  DOI：

  10.1021/acs.jmedchem.6b01055

文献信息

• Discovery of a Chemical Probe Bisamide (CCT251236): An Orally Bioavailable Efficacious Pirin Ligand from a Heat Shock Transcription Factor 1 (HSF1) Phenotypic Screen
  作者：Matthew D. Cheeseman、Nicola E. A. Chessum、Carl S. Rye、A. Elisa Pasqua、Michael J. Tucker、Birgit Wilding、Lindsay E. Evans、Susan Lepri、Meirion Richards、Swee Y. Sharp、Salyha Ali、Martin Rowlands、Lisa O’Fee、Asadh Miah、Angela Hayes、Alan T. Henley、Marissa Powers、Robert te Poele、Emmanuel De Billy、Loredana Pellegrino、Florence Raynaud、Rosemary Burke、Rob L. M. van Montfort、Suzanne A. Eccles、Paul Workman、Keith Jones

  DOI：10.1021/acs.jmedchem.6b01055

  日期：2017.1.12

  Phenotypic screens, which focus on measuring and quantifying discrete cellular changes rather than affinity for individual recombinant proteins, have recently attracted renewed interest as an efficient strategy for drug discovery. In this article, we describe the discovery of a new chemical probe, bisamide (CCT251236), identified using an unbiased phenotypic screen to detect inhibitors of the HSF1 stress pathway. The chemical probe is orally bioavailable and displays efficacy in a human ovarian carcinoma xenograft model. By developing cell:based SAP. and using chemical proteomics, we identified pirin as a high affinity molecular target, which was confirmed by SPR and crystallography.