6-(1-Azetidinyl)-3-(4-methoxyphenyl)pyridazino[4,3-c]isoquinoline | 96825-89-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 6-(1-Azetidinyl)-3-(4-methoxyphenyl)pyridazino[4,3-c]isoquinoline
• 英文别名: Pyridazino(4,3-c)isoquinoline, 6-(1-azetidinyl)-3-(p-methoxyphenyl)-；6-(azetidin-1-yl)-3-(4-methoxyphenyl)pyridazino[4,3-c]isoquinoline
• CAS: 96825-89-7
• 化学式: C₂₁H₁₈N₄O
• 分子量: 342.4
• InChiKey: ISRFFUUSKJOMHT-UHFFFAOYSA-N

物化性质

• 沸点：
  590.8±60.0 °C(Predicted)
• 密度：
  1.299±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  51.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-(4-Methoxy-phenyl)-10-oxa-3,4-diaza-phenanthren-9-one 在 吡啶 、 乙酸铵 、 五氯化磷 、 三氯氧磷 作用下， 以 二乙二醇二甲醚 为溶剂， 反应 21.5h， 生成 6-(1-Azetidinyl)-3-(4-methoxyphenyl)pyridazino[4,3-c]isoquinoline
  参考文献：
  名称：

  Benzodiazepine receptor binding and anticonflict activity in a series of 3,6-disubstituted pyridazino[4,3-c]isoquinolines devoid of anticonvulsant properties

  摘要：

  A series of 3,6-disubstituted pyridazino[4,3-c]isoquinolines were synthesized and tested for their ability to inhibit the binding of [3H]diazepam to rat brain receptors in vitro. Compounds bearing a phenyl, 4-methoxyphenyl, or methyl group at position 3 and a dialkylamino group at position 6 showed the highest affinity in the binding assay and were subsequently evaluated for their anticonflict and anticonvulsant effects. All of these compounds (5a-1 and 5q) were active in the Vogel rat conflict procedure, but none prevented convulsions in mice induced either by metrazol or bicuculline. 3-Phenyl-6-pyrrolidinylpyridazino[4,3-c]isoquinoline (5d) with a Ki = 11.4 nM in the binding assay exhibited the best potency in the anticonflict assay (MED 5 mg/kg ip) and did not produce neuromuscular impairment at the highest dose tested (50 mg/kg ip).

  DOI：

  10.1021/jm00147a034

文献信息

• Pyridazino(4,3-c)isoquinoline derivatives
  申请人：GRUPPO LEPETIT S.p.A.

  公开号：EP0134461A1

  公开（公告）日：1985-03-20

  The present invention is directed to pyridazino [4, 3-c] isoquinolines of Formula I wherein R represents methyl, phenyl or substituted phenyl groups, R1 represents inter alia amino or substituted amino, alkoxy or cycloalkoxy groups, having pharmacological activity, to process for preparing them and to the pharmaceutical compositions containing them. The compounds of the invention possess anti-anxiety activity.

  本发明涉及式 I 的哒嗪并[4，3-c]异喹啉类化合物 其中R代表甲基、苯基或取代苯基，R1代表氨基或取代氨基、烷氧基或环烷氧基等基团，具有药理活性，并涉及制备它们的工艺和含有它们的药物组合物。本发明的化合物具有抗焦虑活性。
• TOJA, E.;TARZIA, G.;BARONE, D.;LUZZANI, F.;GALLICO, L., J. MED. CHEM., 1981, 28, N 9, 1314-1319
  作者：TOJA, E.、TARZIA, G.、BARONE, D.、LUZZANI, F.、GALLICO, L.

  DOI：——

  日期：——
• US4716159A
  申请人：——

  公开号：US4716159A

  公开（公告）日：1987-12-29
• Benzodiazepine receptor binding and anticonflict activity in a series of 3,6-disubstituted pyridazino[4,3-c]isoquinolines devoid of anticonvulsant properties
  作者：Emilio Toja、Giorgio Tarzia、Domenico Barone、Franco Luzzani、Licia Gallico

  DOI：10.1021/jm00147a034

  日期：1985.9

  A series of 3,6-disubstituted pyridazino[4,3-c]isoquinolines were synthesized and tested for their ability to inhibit the binding of [3H]diazepam to rat brain receptors in vitro. Compounds bearing a phenyl, 4-methoxyphenyl, or methyl group at position 3 and a dialkylamino group at position 6 showed the highest affinity in the binding assay and were subsequently evaluated for their anticonflict and anticonvulsant effects. All of these compounds (5a-1 and 5q) were active in the Vogel rat conflict procedure, but none prevented convulsions in mice induced either by metrazol or bicuculline. 3-Phenyl-6-pyrrolidinylpyridazino[4,3-c]isoquinoline (5d) with a Ki = 11.4 nM in the binding assay exhibited the best potency in the anticonflict assay (MED 5 mg/kg ip) and did not produce neuromuscular impairment at the highest dose tested (50 mg/kg ip).