Novel Adrenoceptor Antagonists with a Tricyclic Pyrrolodipyridazine Skeleton

A still unknown tricyclic heterocyclic system (<BO>5</BO>) was synthesized from 6-hydroxy-2-methylpyridazin-3-one and its structure identified as 2,8-dichloro-6-methylpyrrolo[1,2-b:3,4-d‘]dipyridazin-5(6H)-one by spectroscopic investigations. Selective condensation of <BO>5 </BO>with 2-[4-(2-substituted-phenyl)piperazin-1-yl]ethylamine gave the 2-arylpiperazinylethylamino-8-chloro derivatives <BO>6a</BO><BO>−</BO><BO>c</BO>, which were investigated in binding studies toward the three α<INF>1</INF>-adrenergic and 5-HT<INF>1A</INF>-serotonergic receptor subtypes. They displayed high potency on all the assays and some selectivity for α<INF>1a</INF> and α<INF>1d</INF> subtypes.