Alpha1-Adrenoceptor Antagonists. 6. Structural Optimization of Pyridazinone-Arylpiperazines. Study of the Influence on Affinity and Selectivity of Cyclic Substituents at the Pyridazinone Ring and Alkoxy Groups at the Arylpiperazine Moiety

In continuing our search for selective α1-adrenoceptor (AR) antagonists, we have synthesized new alkoxyarylpiperazinylalkylpyridazinone derivatives. The new compounds were tested for their affinity toward α1- and α2-AR and toward the 5-HT1A receptor. α1-AR affinity data are in the subnanomolar range, with 3 showing an affinity of 0.052 nM, about 5-fold higher than prazosin. None of the studied compounds was found to be α1/α2 selective, but 8 showed an interesting 5-HT1A/α1 affinity ratio of 119.