N'-((5-cyanopyrazolo[1,5-a]pyridin-3-yl)methylene)-2-methyl-5-nitrobenzenesulfonohydrazide | 1101118-71-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N'-((5-cyanopyrazolo[1,5-a]pyridin-3-yl)methylene)-2-methyl-5-nitrobenzenesulfonohydrazide
• 英文别名: N'-((5-cyanopyrazolo[1,5-a]pyridin-3-yl)methylene)-2-methyl-5-nitrobenzenesulfono-hydrazide；N-[(5-cyanopyrazolo[1,5-a]pyridin-3-yl)methylideneamino]-2-methyl-5-nitrobenzenesulfonamide
• CAS: 1101118-71-1
• 化学式: C₁₆H₁₂N₆O₄S
• 分子量: 384.375
• InChiKey: ZIADOUJVFAAIHL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  154
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N'-((5-cyanopyrazolo[1,5-a]pyridin-3-yl)methylene)-2-methyl-5-nitrobenzenesulfonohydrazide 、 4-(2-溴乙基)吗啉氢溴酸盐 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以79%的产率得到N'-((5-cyanopyrazolo[1,5-a]pyridin-3-yl)methylene)-2-methyl-N-(2-morpholinoethyl)-5-nitrobenzenesulfonohydrazide
  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
• 作为产物：
  描述：

  异烟酸甲酯 在 硫酸 、 水 、 2,4,6-三甲基苯磺酰羟胺 、 三乙胺 、 三氯氧磷 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 60.03h， 生成 N'-((5-cyanopyrazolo[1,5-a]pyridin-3-yl)methylene)-2-methyl-5-nitrobenzenesulfonohydrazide
  参考文献：
  名称：

  Discovery of pyrazolo[1,5-a]pyridines as p110α-selective PI3 kinase inhibitors

  摘要：

  We have made a novel series of pyrazolo[1,5-a]pyridines as PI3 kinase inhibitors, and demonstrated their selectivity for the p110 alpha isoform over the other Class Ia PI3 kinases. We investigated the SAR around the pyrazolo[1,5-a] pyridine ring system, and found compound 5x to be a particularly potent example (p110 alpha IC50 0.9 nM). This compound inhibits cell proliferation and phosphorylation of Akt/PKB, a downstream marker of PI3 kinase activity, and showed in vivo activity in an HCT-116 human xenograft model. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.11.029

文献信息

• [EN] PYRAZOLO[1,5-A]PYRIDINES AND THEIR USE IN CANCER THERAPY<br/>[FR] PYRAZOLO[1,5-A]PYRIDINES ET LEUR UTILISATION EN CANCÉROTHÉRAPIE
  申请人：AUCKLAND UNISERVICES LTD

  公开号：WO2009008748A1

  公开（公告）日：2009-01-15

  Pyrazolo[1,5-a]pyridines are described, including methods for their preparation, and their use as agents or drugs for cancer therapy, both alone or in combination with radiation and/or other anticancer drugs.

  Pyrazolo[1,5-a]吡啶类化合物被描述，包括它们的制备方法，以及它们作为抗癌治疗药物或药剂的用途，无论是单独使用还是与放疗和/或其他抗癌药物联合使用。
• PYRAZOLO[1,5-a]PYRIDINES AND THEIR USE IN CANCER THERAPY
  申请人：Kendall Jackie Diane

  公开号：US20100226881A1

  公开（公告）日：2010-09-09

  Pyrazolo[1,5-a]pyridines are described, including methods for their preparation, and their use as agents or drugs for cancer therapy, both alone or in combination with radiation and/or other anticancer drugs.

  本文描述了Pyrazolo[1,5-a]pyridines，包括其制备方法，以及其作为单独或与放射治疗和/或其他抗癌药物联合使用的癌症治疗药物或代理。