Design, synthesis and pharmacological activities of 2-substituted 4-phenylquinolines as potential antidepressant drugs

This work represents the design, synthesis, and pharmacological testing of 4-phenylquinoline derivatives as potential antidepressants. Various modifications of substituents at the 2-position of the quinoline ring were tried, and two main series of derivatives were synthesized. In the first series, a...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1985-10, Vol.28 (10), p.1394-1398
Main Authors: Alhaider, Abdulqader A, Abdelkader, M. Atef, Lien, Eric J
Format: Article
Language:English
Subjects:
Animals
Antidepressive Agents - chemical synthesis
Body Temperature Regulation - drug effects
Chemical Phenomena
Chemistry
Exact sciences and technology
Heterocyclic compounds
Heterocyclic compounds with only one n hetero atom and condensed derivatives
Lethal Dose 50
Magnetic Resonance Spectroscopy
Mice
Organic chemistry
Preparations and properties
Quinolines - chemical synthesis
Quinolines - pharmacology
Structure-Activity Relationship
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Summary:This work represents the design, synthesis, and pharmacological testing of 4-phenylquinoline derivatives as potential antidepressants. Various modifications of substituents at the 2-position of the quinoline ring were tried, and two main series of derivatives were synthesized. In the first series, an open (dialkylamino)alkyl chain is linked to the 2-position of the quinoline ring by isosteres. The second approach involved the synthesis of a novel analogue of trazodone with a 4-phenylquinoline grouping replacing the chlorophenyl group of trazodone. The potential antidepressant activity of these new compounds has been demonstrated by their antagonism to the reserpine-induced hypothermia in mice. Both length of the side chain and isosteric displacements within the side chain affect the value of the ED50 obtained. Compounds having three atoms separating the terminal nitrogen from the quinoline ring were found to be more active than those with four atoms. The 2-thia derivatives were devoid of antidepressant activity. Replacement of the open side chain at the 2-position of the quinoline ring by piperazine or substituted piperazines resulted in new compounds that are slightly more potent than imipramine.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00148a004