6-(((1r,4r)-4-hydroxycyclohexyl)amino)-4-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)picolinonitrile | 1262293-97-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 6-(((1r,4r)-4-hydroxycyclohexyl)amino)-4-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)picolinonitrile
• CAS: 1262293-97-9
• 化学式: C₂₅H₂₃N₅O₃S
• 分子量: 473.555
• InChiKey: UTWKGLGMSHGQPM-KESTWPANSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.92
• 重原子数：
  34.0
• 可旋转键数：
  5.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  120.9
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  6-(((1r,4r)-4-hydroxycyclohexyl)amino)-4-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)picolinonitrile 、 三氟乙酸 在 sodium hydroxide 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 0.67h， 生成
  参考文献：
  名称：

  Azaindole-Based Inhibitors of Cdc7 Kinase: Impact of the Pre-DFG Residue, Val 195

  摘要：

  To investigate the role played by the unique pre-DFG residue Val 195 of Cdc7 kinase on the potency of azaindole-chloropyridines (1), a series of novel analogues with various chloro replacements were synthesized and evaluated for their inhibitory activity against Cdc7. X-ray cocrystallization using a surrogate protein, GSK3 beta, and modeling studies confirmed the azaindole motif as the hinge binder. Weaker hydrophobic interactions with Met 134 and Val 195 by certain chloro replacements (e.g., H, methyl) led to reduced Cdc7 inhibition. Meanwhile, data from other replacements (e.g., F, O) indicated that loss of such hydrophobic interaction could be compensated by enhanced hydrogen bonding to Lys 90. Our findings not only provide an in-depth understanding of the pre-DFG residue as another viable position impacting kinase inhibition, they also expand the existing knowledge of ligand-Cdc7 binding.

  DOI：

  10.1021/ml300348c
• 作为产物：
  描述：

  2,6-二氯-4-碘吡啶 在 bis-triphenylphosphine-palladium(II) chloride 、 1,1'-双(二苯基膦)二茂铁 、 tris-(dibenzylideneacetone)dipalladium(0) 、 sodium carbonate 、 锌 作用下， 以 乙醇 、 N,N-二甲基乙酰胺 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成 6-(((1r,4r)-4-hydroxycyclohexyl)amino)-4-(1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)picolinonitrile
  参考文献：
  名称：

  Azaindole-Based Inhibitors of Cdc7 Kinase: Impact of the Pre-DFG Residue, Val 195

  摘要：

  To investigate the role played by the unique pre-DFG residue Val 195 of Cdc7 kinase on the potency of azaindole-chloropyridines (1), a series of novel analogues with various chloro replacements were synthesized and evaluated for their inhibitory activity against Cdc7. X-ray cocrystallization using a surrogate protein, GSK3 beta, and modeling studies confirmed the azaindole motif as the hinge binder. Weaker hydrophobic interactions with Met 134 and Val 195 by certain chloro replacements (e.g., H, methyl) led to reduced Cdc7 inhibition. Meanwhile, data from other replacements (e.g., F, O) indicated that loss of such hydrophobic interaction could be compensated by enhanced hydrogen bonding to Lys 90. Our findings not only provide an in-depth understanding of the pre-DFG residue as another viable position impacting kinase inhibition, they also expand the existing knowledge of ligand-Cdc7 binding.

  DOI：

  10.1021/ml300348c

文献信息

• PYRROLOPYRIDINE INHIBITORS OF KINASES
  申请人：Florjancic Alan S.

  公开号：US20110015173A1

  公开（公告）日：2011-01-20

  The present invention relates to compounds of formula (I) or pharmaceutical acceptable salts, wherein R 1a , R 1b , R 1c , X, and Y are defined in the description. The present invention relates also to compositions containing said compounds which are useful for inhibiting kinases such as Cdc7 and methods of treating diseases such as cancer.

  本发明涉及公式（I）的化合物或药用可接受的盐，其中R1a、R1b、R1c、X和Y在描述中有定义。本发明还涉及含有上述化合物的组合物，该组合物对抑制Cdc7等激酶以及治疗癌症等疾病有用。
• US8435980B2
  申请人：——

  公开号：US8435980B2

  公开（公告）日：2013-05-07