1-(3,5-dibromopyridin-4-yl)piperidine-4-carboxamide | 1221567-46-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-(3,5-dibromopyridin-4-yl)piperidine-4-carboxamide
• CAS: 1221567-46-9
• 化学式: C₁₁H₁₃Br₂N₃O
• 分子量: 363.052
• InChiKey: OYZYBFDHGXEDEP-UHFFFAOYSA-N

物化性质

• 沸点：
  494.5±45.0 °C(Predicted)
• 密度：
  1.764±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  59.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(3,5-dibromopyridin-4-yl)piperidine-4-carboxamide 、 4-三氟甲基苯硼酸 在 四(三苯基膦)钯 potassium phosphate 作用下， 以 甲苯 为溶剂， 反应 1.0h， 以9%的产率得到1-(3-bromo-5-(4-(trifluoromethyl)phenyl)pyridin-4-yl)piperidine-4-carboxamide
  参考文献：
  名称：

  [EN] PYRIDINE AND PYRIMIDINE BASED COMPOUNDS AS WNT SIGNALING PATHWAY INHIBITORS FOR THE TREATMENT OF CANCER
  [FR] COMPOSÉS À BASE DE PYRIDINE ET DE PYRIMIDINE EN TANT QU'INHIBITEURS DE LA VOIE DE SIGNALISATION WNT POUR LE TRAITEMENT DU CANCER

  摘要：

  本发明涉及以吡啶和嘧啶为基础的化合物，包括这些化合物的药物组合物，以及它们作为治疗和/或预防癌症的潜在用途。

  公开号：

  WO2010041054A1
• 作为产物：
  描述：

  哌啶-4-甲酰胺 、 4-氯-3,5-二溴吡啶 在 三乙胺 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 1.0h， 以43%的产率得到1-(3,5-dibromopyridin-4-yl)piperidine-4-carboxamide
  参考文献：
  名称：

  Discovery of Potent, Orally Bioavailable, Small-Molecule Inhibitors of WNT Signaling from a Cell-Based Pathway Screen

  摘要：

  WNT signaling is frequently deregulated in malignancy, particularly in colon cancer, and plays a key role in the generation and maintenance of cancer stem cells. We report the discovery and optimization of a 3,4,5-trisubstituted pyridine 9 using a high-throughput cell-based reporter assay of WNT pathway activity. We demonstrate a twisted conformation about the pyridine-piperidine bond of 9 by small-molecule X-ray crystallography. Medicinal chemistry optimization to maintain this twisted conformation, cognisant of physicochemical properties likely to maintain good cell permeability, led to 74 (CCT251545), a potent small-molecule inhibitor of WNT signaling with good oral pharmacokinetics. We demonstrate inhibition of WNT pathway activity in a solid human tumor xenograft model with evidence for tumor growth inhibition following oral dosing. This work provides a successful example of hypothesis-driven medicinal chemistry optimization from a singleton hit against a cell-based pathway assay without knowledge of the biochemical target.

  DOI：

  10.1021/jm501436m

文献信息

• PYRIDINE AND PYRIMIDINE BASED COMPOUNDS AS WNT SIGNALING PATHWAY INHIBITORS FOR THE TREATMENT OF CANCER
  申请人：McDonald Edward

  公开号：US20110190297A1

  公开（公告）日：2011-08-04

  The present invention relates to pyridine and pyrimidine based compounds, pharmaceutical compositions comprising these compounds and their potential use as therapeutic agents for the treatment and/or prevention of cancer.

  本发明涉及以吡啶和嘧啶为基础的化合物，包括这些化合物的药物组合物以及它们作为治疗和/或预防癌症的治疗剂的潜在用途。
• Pyridine and pyrimidine based compounds as Wnt signaling pathway inhibitors for the treatment of cancer
  申请人：McDonald Edward

  公开号：US08778925B2

  公开（公告）日：2014-07-15

  The present invention relates to pyridine and pyrimidine based compounds, pharmaceutical compositions comprising these compounds and their potential use as therapeutic agents for the treatment and/or prevention of cancer.

  本发明涉及以吡啶和嘧啶为基础的化合物、包含这些化合物的药物组合物以及它们作为治疗和/或预防癌症的潜在治疗剂的用途。
• US8778925B2
  申请人：——

  公开号：US8778925B2

  公开（公告）日：2014-07-15
• [EN] PYRIDINE AND PYRIMIDINE BASED COMPOUNDS AS WNT SIGNALING PATHWAY INHIBITORS FOR THE TREATMENT OF CANCER<br/>[FR] COMPOSÉS À BASE DE PYRIDINE ET DE PYRIMIDINE EN TANT QU'INHIBITEURS DE LA VOIE DE SIGNALISATION WNT POUR LE TRAITEMENT DU CANCER
  申请人：CANCER REC TECH LTD

  公开号：WO2010041054A1

  公开（公告）日：2010-04-15

  The present invention relates to pyridine and pyrimidine based compounds, pharmaceutical compositions comprising these compounds and their potential use as therapeutic agents for the treatment and / or prevention of cancer.

  本发明涉及以吡啶和嘧啶为基础的化合物，包括这些化合物的药物组合物，以及它们作为治疗和/或预防癌症的潜在用途。
• Discovery of Potent, Orally Bioavailable, Small-Molecule Inhibitors of WNT Signaling from a Cell-Based Pathway Screen
  作者：Aurélie Mallinger、Simon Crumpler、Mark Pichowicz、Dennis Waalboer、Mark Stubbs、Olajumoke Adeniji-Popoola、Bozena Wood、Elizabeth Smith、Ching Thai、Alan T. Henley、Katrin Georgi、William Court、Steve Hobbs、Gary Box、Maria-Jesus Ortiz-Ruiz、Melanie Valenti、Alexis De Haven Brandon、Robert TePoele、Birgitta Leuthner、Paul Workman、Wynne Aherne、Oliver Poeschke、Trevor Dale、Dirk Wienke、Christina Esdar、Felix Rohdich、Florence Raynaud、Paul A. Clarke、Suzanne A. Eccles、Frank Stieber、Kai Schiemann、Julian Blagg

  DOI：10.1021/jm501436m

  日期：2015.2.26

  WNT signaling is frequently deregulated in malignancy, particularly in colon cancer, and plays a key role in the generation and maintenance of cancer stem cells. We report the discovery and optimization of a 3,4,5-trisubstituted pyridine 9 using a high-throughput cell-based reporter assay of WNT pathway activity. We demonstrate a twisted conformation about the pyridine-piperidine bond of 9 by small-molecule X-ray crystallography. Medicinal chemistry optimization to maintain this twisted conformation, cognisant of physicochemical properties likely to maintain good cell permeability, led to 74 (CCT251545), a potent small-molecule inhibitor of WNT signaling with good oral pharmacokinetics. We demonstrate inhibition of WNT pathway activity in a solid human tumor xenograft model with evidence for tumor growth inhibition following oral dosing. This work provides a successful example of hypothesis-driven medicinal chemistry optimization from a singleton hit against a cell-based pathway assay without knowledge of the biochemical target.