Synthesis of 1,8-naphthyridine derivatives: potential antihypertensive agents - Part VIII

A series of (ethoxycarbonylpiperazinyl)- and piperazinyl-1,8-naphthyridine derivatives, variously substituted, has been synthesized and pharmacologica lly investigated for anthihypertensive activity. Some of them exhibited a s ignificant and prolonged decrease of the mean arterial pressure (MAP) on sp ontaneously hypertensive rats. On the basis of the pharmacological results, no structure-activity relationship can be deduced at this time. Moreover, the most active compound 4e, was investigated by means of in vitro pharmaco logical functional studies and in vivo, as a diuretic agent, to determine a possible mechanism of the antihypertensive activity, which results in a pr obably non-competitive antagonism against alpha(1), vascular adrenoceptors. This mechanism was also shown by the compounds 8 and 13. (C) Elsevier, Par is.