(E)-2-amino-3-phenyl-6-benzoylimidazo[1,2-b]pyridazine oxime

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (E)-2-amino-3-phenyl-6-benzoylimidazo[1,2-b]pyridazine oxime
• 英文别名: (2-Amino-3-phenyl-imidazo[1,2-b]pyridazin-6-yl)-phenyl-methanone oxime；(NE)-N-[(2-amino-3-phenylimidazo[1,2-b]pyridazin-6-yl)-phenylmethylidene]hydroxylamine
• 化学式: C₁₉H₁₅N₅O
• 分子量: 329.361
• InChiKey: WDHJLIWOZVPJAM-HAVVHWLPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  88.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-bromo-2-phenylacetamide 在 sodium hydroxide 、 盐酸羟胺 、 sodium acetate 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 123.0h， 生成 (E)-2-amino-3-phenyl-6-benzoylimidazo[1,2-b]pyridazine oxime
  参考文献：
  名称：

  Imidazo[1,2-b]pyridazines, Novel Nucleus with Potent and Broad Spectrum Activity against Human Picornaviruses:  Design, Synthesis, and Biological Evaluation

  摘要：

  A novel structural class of picornavirus inhibitors comprising an imidazo[1,2-b]pyridazine nucleus was discovered. 2-Aminoimidazo[1,2-b]pyridazines (6d, (E/Z)-7b, (E)-7d, (Z)-7d, (El Z)-8b, (E)-10b, (E)-13a, (Z)-13a, (E)-13b, (Z)-13b, (E)-13c, and (Z)-13c) were designed and synthesized in an effort to identify potent broad spectrum antirhinoviral agents. A practical synthetic route to this chemical scaffold has been developed. The target compounds were evaluated in a plaque reduction assay and in a cytopathic effect assay. Our preliminary SAR studies highlight the minimum structural features required for antirhinovirus activity. Our data suggest that the nature of the linker between the phenyl and the imidazopyridazine moieties has a significant influence on the activity of these compounds. Oximes are slightly better than vinyl carboxamides at this position. The oximes are the most potent analogues against human rhinovirus 14 (HRV-14), and at the concentrations evaluated, no apparent cellular toxicity is noted. Furthermore, the E geometry appears to be a key element for activity; the Z isomer leads to a considerable loss in potency. Of particular interest, analogue 7b exhibits potent broad-spectrum antirhinoviral and antienteroviral activity when evaluated against a panel of seven additional rhino- and enteroviruses. The chemistry and the biological evaluations are discussed.

  DOI：

  10.1021/jm020583i

文献信息

• Imidazo[1,2-<i>b</i>]pyridazines, Novel Nucleus with Potent and Broad Spectrum Activity against Human Picornaviruses:  Design, Synthesis, and Biological Evaluation
  作者：Chafiq Hamdouchi、Concha Sanchez-Martinez、Joseph Gruber、Miriam del Prado、Javier Lopez、Almudena Rubio、Beverly A. Heinz

  DOI：10.1021/jm020583i

  日期：2003.9.1

  A novel structural class of picornavirus inhibitors comprising an imidazo[1,2-b]pyridazine nucleus was discovered. 2-Aminoimidazo[1,2-b]pyridazines (6d, (E/Z)-7b, (E)-7d, (Z)-7d, (El Z)-8b, (E)-10b, (E)-13a, (Z)-13a, (E)-13b, (Z)-13b, (E)-13c, and (Z)-13c) were designed and synthesized in an effort to identify potent broad spectrum antirhinoviral agents. A practical synthetic route to this chemical scaffold has been developed. The target compounds were evaluated in a plaque reduction assay and in a cytopathic effect assay. Our preliminary SAR studies highlight the minimum structural features required for antirhinovirus activity. Our data suggest that the nature of the linker between the phenyl and the imidazopyridazine moieties has a significant influence on the activity of these compounds. Oximes are slightly better than vinyl carboxamides at this position. The oximes are the most potent analogues against human rhinovirus 14 (HRV-14), and at the concentrations evaluated, no apparent cellular toxicity is noted. Furthermore, the E geometry appears to be a key element for activity; the Z isomer leads to a considerable loss in potency. Of particular interest, analogue 7b exhibits potent broad-spectrum antirhinoviral and antienteroviral activity when evaluated against a panel of seven additional rhino- and enteroviruses. The chemistry and the biological evaluations are discussed.