Synthesis of Some New Pyridazine Derivatives for Anti-HAV Evaluation

Abstract

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