SYNTHESIS AND BIOLOGICAL EVALUATION OF NOVEL IODOPHTHALAZINEDIONE DERIVATIVES AS ANTICONVULSANT AGENTS

In view of their expected anticonvulsant activity, some new derivatives of phthalazine   (I, II, III_a-f, IV, V, VI_a-f and VII_a-h) were designed and synthesized by condensation of Iodophthalic anhydride with hydrazine hydrate to produce iodophthalazindione I which heating with Alc. KOH to give compound II. The compounds III_a-f resulted from condensation of compound II with different alkylcholoroacetates. Compound II_b reacted with ammonia, hydrazinehydrate and different alkyl amines resulted compounds IV, V (hydrazide) and VI respectively. Compound V (hydrazide)  react with different aromatic aldehydes to produce compounds VII_a-h. the final compounds were structurally elucidated basis of IR , ¹HNMR, Ms Carbon, hydrogen and nitrogen analysis. The final compounds were evaluated for anticonvulsant activity using pentylenetetrazole (ptz) to induce convulsion and phenobarbital as reference standard. The compounds I, II, IV, V, VI_a, VI_b, VI_c, VI_d, VI_f, VII_a, VII_b, VII_c and VII_gwere active than Phenobarbital as standard reference the remain compounds less active than Phenobarbital. To under stand the molecular significant of these results we compared the binding modes of these compounds.
Acknalewlgement: Many thanks for Dr. Ahmed Mansour assist. Prof. of pharmacology and Dr. Farg Sherbiny lecturer of organic chemistry