(6-chloropyridazin-3-yl)-(4-methoxy-phenyl)-methanone | 591734-16-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (6-chloropyridazin-3-yl)-(4-methoxy-phenyl)-methanone
• 英文别名: 6-chloro-3-(4-methoxybenzoyl)pyridazine；(6-Chloropyridazin-3-yl)-(4-methoxyphenyl)methanone
• CAS: 591734-16-6
• 化学式: C₁₂H₉ClN₂O₂
• 分子量: 248.669
• InChiKey: OHMZVAVKPIMDAR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  52.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (6-chloropyridazin-3-yl)-(4-methoxy-phenyl)-methanone 在 吡啶 、 氨 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 67.0h， 生成 2,2,2-trifluoro-N-[3-(4-fluorophenyl)-6-(4-methoxybenzoyl)imidazo[1,2-b]pyridazin-2-yl]acetamide
  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
• 作为产物：
  描述：

  3,6-二氯哒嗪 、 对甲氧基苯乙腈 在 potassium tert-butylate 、 双氧水 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 2.5h， 以53%的产率得到(6-chloropyridazin-3-yl)-(4-methoxy-phenyl)-methanone
  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

• Acetonitrile Derivatives as Carbonyl Synthons. One-Pot Preparation of Diheteroaryl Ketones via a Strategy of Sequential S_NAr Substitution and Oxidation
  作者：Zhiwei Yin、Zhongxing Zhang、John F. Kadow、Nicholas A. Meanwell、Tao Wang

  DOI：10.1021/jo030234b

  日期：2004.2.1

  addition of sodium peroxide and aqueous NH4OAc solution effected oxidation to afford aryl heteroaryl ketones in good yields. Aryl acetonitrile derivatives are thus umpolung-type synthons of the corresponding aryl carbonyl functionality.

  2-芳基乙腈衍生物的阴离子与各种杂芳基氯化物或溴化物在S N Ar歧管中反应，得到易于氧化的中间阴离子。加入过氧化钠和NH 4 OAc水溶液进行氧化，以高收率得到芳基杂芳基酮。因此，芳基乙腈衍生物是相应的芳基羰基官能度的umpolung型合成子。