当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Benzodiazepine receptor binding and anticonflict activity in a series of 3,6-disubstituted pyridazino[4,3-c]isoquinolines devoid of anticonvulsant properties.

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

Abstract：

: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).

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Toja E,Tarzia G,Barone D,Luzzani F,Gallico L

doi

10.1021/jm00147a034

subject

Has Abstract

pub_date

1985-09-01 00:00:00

pages

1314-9

issue

9

eissn

0022-2623

issn

1520-4804

journal_volume

28

pub_type

杂志文章

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