Synthesis and anticonvulsant activity of some 2-(2-{1-[substituted phenyl]ethylidene}hydrazinyl)-4-(4-methoxy-phenyl)-6-oxo-1,6-dihydro-pyrimidine-5-carbonitrile

Abstract

A series of dihydro-pyrimidine-5-carbonitrile derivatives (3–16) were synthesized and evaluated for their anticonvulsant activity against MES and scPTZ models. Motor impairment screening was carried out by rotarod test method and CNS depressant effect was determined by Porsolt’s force swim pool method. Compounds 4 and 9 having p-substituted bromo and m-substituted nitro groups, respectively, were found to be most active showing activity both in MES and scPTZ screen at lower doses of 30 mgkg⁻¹ at 0.5 h and 100 mgkg⁻¹ at 4 h. In the rotarod motor impairment screen, compound 4 did not show any motor impairment even at the maximum dose of 300 mgkg⁻¹; however, compound 9 showed motor impairment at 300 mgkg⁻¹ dose after 4.0 h. The compounds were also tested for their CNS depression effect. The compounds 4 and 9 showed 41.38 and 43.44% increase in immobility time with respect to control. The pharmacophore hypothesis also fits best for compounds 4 and 9.

Keywords::

• Cyanopyrimidine derivatives
• Schiff’s Base
• Anticonvulsant
• Neurotoxicity
• CNS depression activity

Acknowledgements

The authors are thankful to Jamia Hamdard (New Delhi) for providing research facilities to pursue this work.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.