New 4-(4-methyl-phenyl)phthalazin-1(2H)-one derivatives and their effects on α1-receptors

Continuing our research aimed at obtaining new compounds with high affinity and selectivity toward α1-AR, a new series of arylpiperazine derivatives was designed, synthesized, and biologically tested. The new compounds 1–17 are characterized by a phenylphthalazin-1(2H)-one fragment connected through an alkyl chain to an arylpiperazine residue. The pharmacological profile of these compounds was evaluated for their affinity and selectivity toward α1-AR, α2-AR and toward 5HT1A serotoninergic receptor. A discussion on the structure–activity relationship (SAR) of these compounds is also reported.

Graphical abstractContinuing our research aimed at obtaining new compounds with high affinity and selectivity toward α1-AR, a new class of arylpiperazine derivatives has been synthesized. The new compounds are characterized by a 4-methyl-phenyl-phthalazinone system linked, through a linker of two-, four- or seven-carbon atoms, to an arylpiperazine moiety. The pharmacological profile of these compounds was evaluated for their affinities toward α1- and α2-AR, and toward 5HT1A receptor. A discussion on the structure–activity relationship of such compounds is also reported.Figure optionsDownload full-size imageDownload as PowerPoint slide