Synthesis of new pyridazinone derivatives and their affinity towards α 1–α 2-adrenoceptors

Abstract

A series of 3(2 H)-pyridazinone derivatives was evaluated for their affinity in vitro towards α 1–α 2-adrenoceptors by radioligand receptor binding assays. All target compounds showed good affinities for the α 1-adrenoceptor (with K i values in the subnanomolar range), and a gradual increase in affinity was observed by increasing the polymethylene chain length of this series up to a maximum of six and seven carbon atoms, when the fragment 4-[2-(2-methoxyphenoxy)-ethyl]-1-piperazinyl is linked in 5 position of the 3(2 H)-pyridazinone ring, while a slight decrease was found for the higher homologues. Increasing the chain length when the 4-[2-(2-methoxyphenoxy)-ethyl]-1-piperazinyl group is linked in 6 position of the 3(2 H)-pyridazinone ring, had a different effect: there is the highest affinity when the polymethylene chain is of four carbon atoms. The alkylic chain, a spacer between the two major constituents of the molecule, can influence the affinity and the selectivity.