Design, Synthesis, and a1-Adrenoceptor Binding Properties of New Arylpiperazine Derivatives bearing a Flavone Nucleus as the Terminal Heterocyclic Molecular Portion

Following our research project aimed at obtaining new compounds with high affinity and selectivity toward α1-adrenoceptors (AR), a new class of piperazine derivatives was designed, synthesized and biologically tested. The new compounds 1-13 are characterized by a flavone system linked, through an ethoxy or propoxy spacer, to a phenyl- or pyridazinone-piperazine moiety. Biological data showed an interesting profile for the phenylpiperazine subclass found to have a nanomolar affinity toward α1-AR, and less pronounced affinity for α2-AR and the 5-HT1A serotoninergic receptor. A discussion on the structure-activity relationship (SAR) of such compounds is also reported, on the basis of the flavone substitution pattern, length and functionalization of the spacer, and disruption of the phenylpiperazine system.