SYNTHESIS AND EVALUATION OF NITROGEN HETEROCYCLIC COMPOUNDS OF ANTITUMOR EFFECTS

Abstract

(CLXVIIIa-g) respectively. The biological activity of many drugs containing the thiohydantoin moiety led many investigators to synthesize several new compouunds containing this moeity and evaluate their pharmacological activites as antitumor and antiviral agents. Our research work at the National Organi­ zation for Drug Control and Research is usually oriented to the chemistry of biologically active compounds.

In this investigation, the following two topics are studied :

a) Synthesis and reactions of some thiohydantoin derivatives. b) Evaluation of the antitumor and aniiviral activities of the compounds obtained.

a) Synthesis and reactions of some thiohydantoin derivatives :

2-Thiohydantoin condenses with salicylaldehyde, furfural, and N,N-dimethyl-p-aminobenzaldehyde to give the corresponding arylidene derivatives (CLXIIa-c). Alkylation of these arylidenederivatives with alkyl iodides in alkaline medium leads to S-alkylation with the formation of the corresponding 2-S-alkyl derivatives (CLXIIIa-g). When the latter derivatives are allowed to react with hydrazine hydrate or phenyl­ hydrazine in boiling ethanol, the corresponding 2-hydrazino derivatives (CLXIVa-c) and 2-phenyl hydrazino derivatives (CLXIVd-f) are formed with the removal of the S-alkyl group.

Condensation of the hydrazino derivatives (CLXIVa-c) with benzaldehyde, salicylaldehyde, furfural and N,N-dimethyl-p-amino­ benzaldehyde gives the corresponding Schiffs bases (CLXVa-1).

Phosphorus oxychloride reacts with the 2-alkylmercapto-5-arylidene derivatives (CLXIIla-g) to give the corresponding 4-chloroimidazoles (CLXVIa-g).

It was interesting to test the reactivity of chlorine atom in the latter compounds (CLXVIa-g) towards some nitrogen nucleophiles. Thus, the 4-choroimidazoles (CLXVIa-g) react with p-toluidine, and hydrazine to give the 4-(p-tolylamino) (CLXVIIa-g) and 4-hydrazino derivatives