A series of 3(2H)-pyridazinone derivatives was evaluated for their affinity in vitro towards alpha(1)-alpha(2)-adrenoceptors by radioligand receptor binding assays. All target compounds showed good affinities for the alpha(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(2H)-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(2H)-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. (C) 1999 Elsevier Science Ltd. All rights reserved.
|Autori:||Corsano S; Strappaghetti G; Barbaro R; Giannaccini G; Betti L; Lucacchini A|
|Titolo:||Synthesis of new pyridazinone derivatives and their affinity towards alpha(1)-alpha(2)-adrenoceptors|
|Anno del prodotto:||1999|
|Digital Object Identifier (DOI):||10.1016/S0968-0896(99)00046-2|
|Appare nelle tipologie:||1.1 Articolo in rivista|