Synthesis and anticonvulsant activity of some 1-cyclohexylidine/ cycloheptylidine-4-substitued semicarbazide derivatives

Abstract

Aryl semicarbazide derivatives are reported to possess anticonvulsant activity. On the other hand unsubstituted and small substituents (less than 3 carbon atom) containing cyclohexanones prevented both pentylenetetrazole and MES induced seizures. Similarly cycloheptanone fused with benzodiazepine and furan produced anticonvulsant compounds. Therefore looking into the above facts in the present study, we have synthesized 12 derivatives of 1-cyclohexylidine/cycloheptylidine-4-substitued semicarbazide derivatives and screened them for anticonvulsant activity. The synthesis of compounds was achieved as follows: The various para substituted (H, CH3, F,Cl,Br, I) anilines were converted to aryl ureas by reacting with sodium cyanate in the presence of glacial acetic acid. These aryl ureas and aryl semicarbazides were synthesized by allowing them to react with hydrazine hydrate. Finally the aryl semicarbazides were condensed with cyclohexanone/ cycloheptanone in the presence of sodium acetate to give title compounds. All the synthesized compounds were evaluated for anticonvulsant activity by MES method using carbamazepine as standard and it was observed that all the compounds possess anticonvulsant activity comparable to carbamazepine. Carbamazepine had shown the abolition in the hind limb extensor tonic convulsion after 2 sec. whereas few compounds i.e. 1-cyclohexylidine-4-(4-fluorophenyl) semicarbazide, 1-cycloheptylidine-4-(4- fluorophenyl) semi-carbazide and 1-cycloheptylidine-4-phenylsemicarbazide were more active than standard. Overall it was found that cycloheptyl containing compounds were more active than cyclohexyl containing compounds. The unsubstitued compounds were more active than halo derivatives i.e. electron withdrawing groups, and halo compounds were more active than methyl derivatives i.e. electron donating group (CH3). The order of activity for cyclohexanone and cycloheptanone derivatives is as follows: H >F >Cl >Br >I >CH3. Among the halo derivatives, the activity decreased with increasing molecular weight of halo substituents.