2-[[8-oxo-2-(1H-pyrazol-4-yl)-7H-pyrido[3,4-d]pyrimidin-4-yl]amino]cyclopentane-1-carbonitrile | 1470249-04-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 2-[[8-oxo-2-(1H-pyrazol-4-yl)-7H-pyrido[3,4-d]pyrimidin-4-yl]amino]cyclopentane-1-carbonitrile
• CAS: 1470249-04-7
• 化学式: C₁₆H₁₅N₇O
• 分子量: 321.341
• InChiKey: VQNBXWDMQVKMEV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  119
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-甲氧基-3-氨基吡啶-4-羧酸 在 bis-triphenylphosphine-palladium(II) chloride 、 palladium on activated charcoal 、 氨 、 氢气 、 sodium carbonate 、 N,N-二异丙基乙胺 、 N,N'-羰基二咪唑 、 三氯氧磷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 乙酸乙酯 为溶剂， 反应 42.0h， 生成 2-[[8-oxo-2-(1H-pyrazol-4-yl)-7H-pyrido[3,4-d]pyrimidin-4-yl]amino]cyclopentane-1-carbonitrile
  参考文献：
  名称：

  Design and evaluation of novel 8-oxo-pyridopyrimidine Jak1/2 inhibitors

  摘要：

  A highly ligand efficient, novel 8-oxo-pyridopyrimidine containing inhibitor of Jak1 and Jak2 isoforms with a pyridone moiety as the hinge-binding motif was discovered. Structure-based design strategies were applied to significantly improve enzyme potency and the polarity of the molecule was adjusted to gain cellular activity. The crystal structures of two representative inhibitors bound to Jak1 were obtained to enable SAR exploration. (C) 2013 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2013.08.082

文献信息

• Design and evaluation of novel 8-oxo-pyridopyrimidine Jak1/2 inhibitors
  作者：Sharada Labadie、Kathy Barrett、Wade S. Blair、Christine Chang、Gauri Deshmukh、Charles Eigenbrot、Paul Gibbons、Adam Johnson、Jane R. Kenny、Pawan Bir Kohli、Marya Liimatta、Patrick J. Lupardus、Steven Shia、Micah Steffek、Savita Ubhayakar、Anne van Abbema、Mark Zak

  DOI：10.1016/j.bmcl.2013.08.082

  日期：2013.11

  A highly ligand efficient, novel 8-oxo-pyridopyrimidine containing inhibitor of Jak1 and Jak2 isoforms with a pyridone moiety as the hinge-binding motif was discovered. Structure-based design strategies were applied to significantly improve enzyme potency and the polarity of the molecule was adjusted to gain cellular activity. The crystal structures of two representative inhibitors bound to Jak1 were obtained to enable SAR exploration. (C) 2013 Published by Elsevier Ltd.