N'-((6-bromoimidazo[1,2-a]pyridin-3-yl)methylene)-2-methyl-5-nitrobenzenesulfonohydrazide | 945619-40-9

• 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'-((6-bromoimidazo[1,2-a]pyridin-3-yl)methylene)-2-methyl-5-nitrobenzenesulfonohydrazide
• 英文别名: Imidazopyridine derivative, 7c；N-[(E)-(6-bromoimidazo[1,2-a]pyridin-3-yl)methylideneamino]-2-methyl-5-nitrobenzenesulfonamide
• CAS: 945619-40-9
• 化学式: C₁₅H₁₂BrN₅O₄S
• 分子量: 438.261
• InChiKey: ZFLTXSSEUQFHCZ-QGMBQPNBSA-N

物化性质

• 密度：
  1.74±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  130
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  重氮甲烷 、 N'-((6-bromoimidazo[1,2-a]pyridin-3-yl)methylene)-2-methyl-5-nitrobenzenesulfonohydrazide 以 四氢呋喃 、 乙醚 为溶剂， 以83%的产率得到2-甲基-5-硝基苯磺酸(2E)-2-[(6-溴咪唑并[1,2-A]吡啶-3-基)亚甲基]-1-甲酰肼
  参考文献：
  名称：

  Synthesis, biological evaluation and molecular modelling of sulfonohydrazides as selective PI3K p110α inhibitors

  摘要：

  A series of 2-methyl-5-nitrobenzenesulfonohydrazides were prepared and evaluated as inhibitors of PI3K. An isoquinoline derivative shows good selectivity for the p110 alpha isoform over p110 beta and p110 delta, and also demonstrates good in vitro activity in a cell proliferation assay. Molecular modelling provides a rationalisation for the observed SAR. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.08.062
• 作为产物：
  描述：

  (E)-(6-bromoimidazo[1,2-a]pyridin-3-yl)methylidenehydrazine 、 2-甲基-5-硝基苯磺酰氯 在 吡啶 作用下， 反应 5.0h， 生成 N'-((6-bromoimidazo[1,2-a]pyridin-3-yl)methylene)-2-methyl-5-nitrobenzenesulfonohydrazide
  参考文献：
  名称：

  Synthesis and biological evaluation of sulfonylhydrazone-substituted imidazo[1,2-a]pyridines as novel PI3 kinase p110α inhibitors

  摘要：

  We have previously reported the imidazo[1,2-a]pyridine derivative 4 as a novel p110 alpha inhibitor; however, although 4 is a potent inhibitor of p110 alpha enzymatic activity and tumor cell proliferation in vitro, it is unstable in solution and ineffective in vivo. To increase stability the pyrazole of 4 was replaced with a hydrazone and a moderately potent p110 alpha inhibitor 7a was obtained. Subsequent optimization of 7a afforded exceptionally potent p110 alpha inhibitors, including 8c and 8h, with IC(50) values of 0.30 nM and 0.26 nM, respectively; to the best of our knowledge, these compounds are the most potent PI3K p110 alpha inhibitors reported to date. Compound 8c was also stable in solution and exhibited significant anti-tumor effectiveness in vivo. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.05.070

文献信息

• [EN] PIK3/P110a INHIBITORS FOR PREVENTION OF RESTENOSIS BY APPLICATION AS AN IMPLANT COATING<br/>[FR] INHIBITEURS DE PIK3/P110? POUR LA PRÉVENTION DE LA RESTÉNOSE PAR APPLICATION SOUS LA FORME D'UN REVÊTEMENT POUR IMPLANT
  申请人：UNIV ZUERICH

  公开号：WO2012156379A1

  公开（公告）日：2012-11-22

  The invention relates to medical implant having a basic body comprising an inhibitor of p110α incorporated into or coated onto the basic body. As inhibitor, N-[(6-bromoimidazo[1,2-a]pyridin-3-yl) methyleneamino]-N,2-dimethyl-5-nitro-benzenesulfonamide is preferred. The invention further relates to a coating of an implant, and a second indication medical use of N-[(6-bromoimidazo[1,2-a]pyridin-3-yl) methyleneamino]-N,2-dimethyl-5-nitro-benzenesulfonamide for the prevention of restenosis as a coating on medical implants.
• Synthesis, biological evaluation and molecular modelling of sulfonohydrazides as selective PI3K p110α inhibitors
  作者：Jackie D. Kendall、Gordon W. Rewcastle、Raphael Frederick、Claire Mawson、William A. Denny、Elaine S. Marshall、Bruce C. Baguley、Claire Chaussade、Shaun P. Jackson、Peter R. Shepherd

  DOI：10.1016/j.bmc.2007.08.062

  日期：2007.12

  A series of 2-methyl-5-nitrobenzenesulfonohydrazides were prepared and evaluated as inhibitors of PI3K. An isoquinoline derivative shows good selectivity for the p110 alpha isoform over p110 beta and p110 delta, and also demonstrates good in vitro activity in a cell proliferation assay. Molecular modelling provides a rationalisation for the observed SAR. (c) 2007 Elsevier Ltd. All rights reserved.
• Synthesis and biological evaluation of sulfonylhydrazone-substituted imidazo[1,2-a]pyridines as novel PI3 kinase p110α inhibitors
  作者：Masahiko Hayakawa、Ken-ichi Kawaguchi、Hiroyuki Kaizawa、Tomonobu Koizumi、Takahide Ohishi、Mayumi Yamano、Minoru Okada、Mitsuaki Ohta、Shin-ichi Tsukamoto、Florence I. Raynaud

  DOI：10.1016/j.bmc.2007.05.070

  日期：2007.9.1

  We have previously reported the imidazo[1,2-a]pyridine derivative 4 as a novel p110 alpha inhibitor; however, although 4 is a potent inhibitor of p110 alpha enzymatic activity and tumor cell proliferation in vitro, it is unstable in solution and ineffective in vivo. To increase stability the pyrazole of 4 was replaced with a hydrazone and a moderately potent p110 alpha inhibitor 7a was obtained. Subsequent optimization of 7a afforded exceptionally potent p110 alpha inhibitors, including 8c and 8h, with IC(50) values of 0.30 nM and 0.26 nM, respectively; to the best of our knowledge, these compounds are the most potent PI3K p110 alpha inhibitors reported to date. Compound 8c was also stable in solution and exhibited significant anti-tumor effectiveness in vivo. (c) 2007 Elsevier Ltd. All rights reserved.