N'-((5-cyanopyrazolo[1,5-a]pyridin-3-yl)methylene)-N-methyl-3-nitrobenzohydrazide | 1101119-59-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并吡啶类
• 英文名称: N'-((5-cyanopyrazolo[1,5-a]pyridin-3-yl)methylene)-N-methyl-3-nitrobenzohydrazide
• 英文别名: N-[(5-cyanopyrazolo[1,5-a]pyridin-3-yl)methylideneamino]-N-methyl-3-nitrobenzamide
• CAS: 1101119-59-8
• 化学式: C₁₇H₁₂N₆O₃
• 分子量: 348.321
• InChiKey: CUFHYKVWHFYLLP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  120
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-甲酰吡唑并[1,5-a]吡啶-5-甲腈 、 甲基肼硫酸盐 、 间硝基苯甲酰氯 在 碳酸氢钠 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以90%的产率得到N'-((5-cyanopyrazolo[1,5-a]pyridin-3-yl)methylene)-N-methyl-3-nitrobenzohydrazide
  参考文献：
  名称：

  Novel pyrazolo[1,5-a]pyridines as p110α-selective PI3 kinase inhibitors: Exploring the benzenesulfonohydrazide SAR

  摘要：

  Structure-activity relationship studies of the pyrazolo[1,5-a]pyridine class of PI3 kinase inhibitors show that substitution off the hydrazone nitrogen and replacement of the sulfonyl both gave a loss of p110 alpha selectivity, with the exception of an N-hydroxyethyl analogue. Limited substitutions were tolerated around the phenyl ring; in particular the 2,5-substitution pattern was important for PI3 kinase activity. The N-hydroxyethyl compound also showed good inhibition of cell proliferation and inhibition of phosphorylation of Akt/PKB, a downstream marker of PI3 kinase activity. It had suitable pharmacokinetics for evaluation in vivo, and showed tumour growth inhibition in two human tumour cell lines in xenograft studies. This work has provided suggestions for the design of more soluble analogues. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.11.031

文献信息

• Novel pyrazolo[1,5-a]pyridines as p110α-selective PI3 kinase inhibitors: Exploring the benzenesulfonohydrazide SAR
  作者：Jackie D. Kendall、Anna C. Giddens、Kit Yee Tsang、Raphaël Frédérick、Elaine S. Marshall、Ripudaman Singh、Claire L. Lill、Woo-Jeong Lee、Sharada Kolekar、Mindy Chao、Alisha Malik、Shuqiao Yu、Claire Chaussade、Christina Buchanan、Gordon W. Rewcastle、Bruce C. Baguley、Jack U. Flanagan、Stephen M.F. Jamieson、William A. Denny、Peter R. Shepherd

  DOI：10.1016/j.bmc.2011.11.031

  日期：2012.1

  Structure-activity relationship studies of the pyrazolo[1,5-a]pyridine class of PI3 kinase inhibitors show that substitution off the hydrazone nitrogen and replacement of the sulfonyl both gave a loss of p110 alpha selectivity, with the exception of an N-hydroxyethyl analogue. Limited substitutions were tolerated around the phenyl ring; in particular the 2,5-substitution pattern was important for PI3 kinase activity. The N-hydroxyethyl compound also showed good inhibition of cell proliferation and inhibition of phosphorylation of Akt/PKB, a downstream marker of PI3 kinase activity. It had suitable pharmacokinetics for evaluation in vivo, and showed tumour growth inhibition in two human tumour cell lines in xenograft studies. This work has provided suggestions for the design of more soluble analogues. (C) 2011 Elsevier Ltd. All rights reserved.