5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-3-carboxylic acid | 944906-73-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并吡啶类
• 英文名称: 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-3-carboxylic acid
• 英文别名: 5,6,7,8-Tetrahydro[1,2,4]triazolo[4,3-A]pyridine-3-carboxylic acid
• CAS: 944906-73-4
• 化学式: C₇H₉N₃O₂
• mdl: MFCD09055280
• 分子量: 167.167
• InChiKey: UICYCSNBARDCJH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.571
• 拓扑面积：
  68
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-chloro-4-(trans-3-amino-2,2,4,4-tetramethylcyclobutoxy)benzonitrile 、 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-3-carboxylic acid 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 N-((1r,3r)-3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyridine-3-carboxamide
  参考文献：
  名称：

  Systematic Structure Modifications of Imidazo[1,2-a]pyrimidine to Reduce Metabolism Mediated by Aldehyde Oxidase (AO)

  摘要：

  N-{trans-3-[(5-Cyano-6-methylpyridin-2-yl)oxy] 2,2,4,4-tetramethylcyclobutyl}imidazo [1,2-a]pyrimidine-3-carboxamide (1) was recently identified as a full antagonist of the androgen receptor, demonstrating excellent in vivo tumor growth inhibition in castration-resistant prostate cancer (CRPC). However, the imidazo[1,2-a]pyrimidine moiety is rapidly metabolized by aldehyde oxidase (AO). The present paper describes a number of medicinal chemistry strategies taken to avoid the AO-mediated oxidation of this particular system. Guided by an AO protein structure-based model, our investigation revealed the most probable site of AO oxidation and the observation that altering the heterocycle or blocking the reactive site are two of the more effective strategies for reducing AO metabolism. These strategies may be useful for other drug discovery programs.

  DOI：

  10.1021/jm2010942

文献信息

• PYRROLO[2,3-D]PYRIMIDINE DERIVATIVES AS INHIBITORS OF TROPOMYOSIN-RELATED KINASES
  申请人：Pfizer Limited

  公开号：EP2694509B1

  公开（公告）日：2016-05-18