The pharmacological activity of derivatives of 4-oxo-3,4-dihydroquinazoline and anthranilamides containing a fragment of glycine
Keywords:quinazolone, anthranilamide, antidepressant effect, anticonvulsant activity, hypnotic activity
AbstractDerivatives of 4-oxo-3,4-dihydroquinazoline are known as a promising class of compounds due to their wide spectrum of the pharmacological activity. Taking into account the PASS data for the substituted anthranilamides synthesized, as well as derivatives of 4-oxo-3,4-dihydroquinazoline containing an “in-built” fragment of amino acid glycine as a pharmacophore, the decision to study their central neurotropic effects was made. While studying the hypnotic, anticonvulsant and antidepressant activities the highest antidepressant properties of N-(1,1-diphenyl-1-hydroxyet-2-yl)-N'-diphenylhydroxyacetylanthranilamide (compound 4) have been determined, this compound is slightly inferior the reference drug Imipramine. N-(phenylhydrazidoacetyl)-N'-succinamidoanthranilamide (compound 1) reveals high anticonvulsant properties and is not inferior the classical anticonvulsant drug Depakine. When studying the hypnotic effect the antagonism with Barbamyl for 2-(4-oxo-3,4-dihydro-3-quinazolinyl)acetohydrazide (compound 5) has been found. Methyl-(2-methylcarbonyloxymethyl-4-oxo-3,4-dihydro-3-quinazolinyl)acetate (compound 8) decreased the latent period of “falling asleep” for animals in 1.6 and 1.7 times in the doses of 20 and 200 mg/kg, respectively (the same level with the reference drug), and therefore, it is a promising compound for further research of the hypnotic activity. The analysis of the “structure-activity” relationship gives the possibility to assume that such pronounced pharmacological activity is due to the presence of substituents in position 2 of the quinazoline nucleus. Therefore, the data obtained prove that the study of these derivatives is promising for further search of new biologically active substances with hypnotic, anticonvulsant and antidepressant properties.
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