Synthesis of Some New Pyridazine Derivatives for Anti-HAV Evaluation.

4-(2-(4-Halophenyl)hydrazinyl)-6-phenylpyridazin-3(2 H )-ones 1a , b were prepared and treated with phosphorus oxychloride, phosphorus pentasulphide and ethyl chloroformate to give the corresponding chloropyridazine, pyridazinethione, oxazolopyridazine derivatives 2 - 4 , respectively. Compound 2 reacted with hydrazine hydrate to afford hydrazinylpyridazine 7 . The reaction of 4-(2-(4-chlorophenyl)hydrazinyl)-3-hydrazinyl-6-phenylpyridazine ( 7 ) with acetic anhydride, p -chlorobenzaldehyde and carbon disulphide gave the corresponding pyridazinotriazine derivatives 8 - 10 . On the other hand, 5-(4-chlorophenylamino)-7-(3,5-dimethoxybenzylidene)-3-phenyl-5 H -pyridazino[3,4- b ][1,4]thiazin-6(7 H )-one ( 11 ) was prepared directly from the reaction of compound 3 with chloroacetic acid in presence of p -chlorobenzaldehyde. Compound 11 reacted with nitrogen nucleophiles (hydroxylamine hydrochloride, hydrazine hydrate) and active methylene group-containing reagents (malononitrile, ethyl cyanoacetate) to afford the corresponding fused compounds 12 - 15 , respectively. Pharmacological screening for antiviral activity against hepatitis A virus (HAV) was performed for the new compounds. 4-(4-Chlorophenylamino)-6-phenyl-1,2-dihydropyridazino[4,3- e ][1,2,4]triazine-3(4 H )-thione ( 10 ) showed the highest effect against HAV.