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

This study comprises a brief literature survey on cancer, its causes and treatment as well as biological activities and chemistry of pyridazine and fused pyridazine derivatives. The thesis involves design of some new pyridazine and fused pyridazine derivatives aiming to possess an anticancer activity through inhibition of VEGFR. The Schemes followed for the preparation of the designed compounds are summarized asfollows: Scheme (1) starts with the preparation of the root compound N-carbamimidoyl-4-[(6-chloropyridazin-3-yl) amino]benzenesulphonamide (I) followed by reaction with different aromatic amines to give N-Carbamimidoyl-4- [(6-arylaminopyridazin-3-yl)amino]benzenesulphonamides IIa-f. Scheme (2) involves nucleophilic substitution reaction of compound I with meta and para phenylenediamine to give the relevant compounds IIIa, b. Furthermore, compound IIIa was reacted with each of acetyl chloride and 3-chloropropionyl chloride to give the corresponding pyridazine derivatives IVa, b respectively. Further, compounds IIIa, b were reacted with different alkyl isothiocyanates to give the corresponding thiourea compounds Va-d and VIa-d. On the other hand, scheme (3A) involves the reaction of compound I with each of 2-aminophenol, different substituted anthranilic acids and 2-aminonicotinic acid to give the corresponding pyridazino [1,6-a] benzimidazole VII, pyridazino [6,1-b] quinazolines VIIIa,c,d and pyrido [2{u2019}, 3{u2019},4,5] pyrimido [1,2- b]pyridazine VIIIb respectively

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