Synthesis of new pyridazinone derivatives and their affinity towards alpha(1)-alpha(2)-adrenoceptors

A series of 3(2H)-pyridazinone derivatives was evaluated for their affinity in vitro towards alpha(1)-alpha(2)-adrenoceptors by radioligand receptor b inding assays. All target compounds showed good affinities for the alpha(1) -adrenoceptor (with K-i values in the subnanomolar range), and a gradual in crease in affinity was observed by increasing the polymethylene chain lengt h of this series up to a maximum of six and seven carbon atoms, when the fr agment 4-[2-(2-methoxyphenoxy)-ethyl]-1-piperazinyl is linked in 5 position of the 3(2H)-pyridazinone ring, while a slight decrease was found for the higher homologues. Increasing the chain length when the 4-[2-(2-methoxyphen oxy)-ethyl]-1-piperazinyl group is linked in 6 position of the 3(2H)-pyrida zinone ring, had a different effect: there is the highest affinity when the polymethylene chain is of four carbon atoms. The alkylic chain, a spacer b etween the two major constituents of the molecule, can influence the affini ty and the selectivity. (C) 1999 Elsevier Science Ltd. All rights reserved.