Synthesis and antihypertensive activity of new 6-heteroaryl-3-hydrazinopyridazine derivatives

The synthesis and pharmacological activity of new 6-heteroaryl-3-hydrazinopyridazines with antihypertensive action are described. The introduction of pyrrole, pyrazole, imidazole, triazole, tetrazole, thiophene, indole, and carbazole heterocyclic rings into the 6 position of the pyridazine nucleus has been carried out by three different methods of synthesis. The hypotensive action has been examined on normotensive and spontaneously hypertensive rats by comparison with dihydralazine (I). 6-Imidazol-1-yl derivatives have proved particularly active. Of these derivatives, 3-hydrazino-6-(2-methylimidazol-1-yl)pyridazine (7c) achieves 4.9 times the activity of dihydralazine when administered orally to spontaneously hypertensive rats. The LD50 values of 7c and dihydralazine are very similar.