Synthesis and anticonvulsant evaluation of some substituted-1,3-diazaspiro decan-4-one derivatives / Rasha Mohamed Mohamed Hassan ; Supervised M. Nabil Youssef Aboul-Enein , Kamilia Mahmoud Amin

Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmaceutical Chemistry

The search for anticonvulsant compounds with selective activity and less toxicity continues to be an area of intensive research in medicinal chemistry. Thus, in this work, the first part deals with the synthesis of certain substituted spiroimidazolidinones (1,3-diazaspiro[4.5]decan-4-ones) VIa-d and VIIIa-x and evaluation of their anticonvulsant properties. Also, in this part a molecular modeling study was performed for the designed target compounds. Moreover, in the second part, the enantioseparation of the racemic derivatives VIc-d and VIIIm-x using different polysaccharide type chiral stationary phases (CSPs), namely, Chiralcel OJ, Chiralcel OD and Lux {u2013}amylose-2 has been studied. Accordingly, this thesis is divided into two parts including the following sections: A) Part I Introduction: This part includes the mechanism of action of antiepileptic drugs and a review on the different biological activities of imidazolidines, imidazolidine-2-one and imidazolidine-4-one moieties as well as their methods for synthesis. Aim of the Present Work: This section discusses the rationale on which the design of the synthesized compounds was based, in addition to the schemes followed in their synthesis. Theoretical Discussion: This section addresses the reactions followed in the synthesis of the new target compounds VIa- d and VIIIa-x, in addition to intermediates needed in their preparation. The strategies followed for the synthesis of the designed compounds, as well as starting materials and intermediates have been described in Schemes I and II.

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