Synthesis of new pyridazinone derivatives and their affinity towards alpha1-alpha2-adrenoceptors.
A series of 3(2H)-pyridazinone derivatives was evaluated for their affinity in vitro towards alpha1-alpha2-adrenoceptors by radioligand receptor binding assays. All target compounds showed good affinities for the alpha1-adrenoceptor (with Ki 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.
Corsano
S
S
Istituto di Chimica e Tecnologia del Farmaco, Università di Perugia, Italy.
Strappaghetti
G
G
Barbaro
R
R
Giannaccini
G
G
Betti
L
L
Lucacchini
A
A
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects; D066298:In Vitro Techniques; D007700:Kinetics; D008956:Models, Chemical; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*
D011724:Pyridazines; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2