A series of 4-(N-methylencycloalkylamino)-1,8-naphthyridine derivatives variously substituted in positions 2 and 7 were synthesized and pharmacologically investigated for possible antihypertensive activity. These compounds were tested to determine a possible vasodilator mechanism of action. Compounds 22, 23, 27-29, 47 and 48 showed satisfactory levels of potency (pIC(50) > 5), which in one case (compound 23) reached a really interesting value (pIC(50) 6.92). Furthermore, for some selected compounds (19, 22, 23, 26, 28, 29, 47), the vasorelaxing activity was also evaluated in the presence of the guanylate cyclase blocker ODQ or of the adenylate cyclase blocker SQ 22536, and some of these can be considered as possible guanylate-cyclase inhibitors. Finally, compounds 19, 22 and 23 were also tested in the presence of the ATP-sensitive potassium channel blocker glybenclamide and seem to possess activating properties on these potassium channels. (C) 2001 Editions scientifiques et medicales Elsevier SAS.
Synthesis and evaluation of antihypertensive activity of 1,8-naphthyridine derivatives. Part X
CALDERONE, VINCENZO;MANERA, CLEMENTINA;SACCOMANNI, GIUSEPPE;TESTAI, LARA
2001-01-01
Abstract
A series of 4-(N-methylencycloalkylamino)-1,8-naphthyridine derivatives variously substituted in positions 2 and 7 were synthesized and pharmacologically investigated for possible antihypertensive activity. These compounds were tested to determine a possible vasodilator mechanism of action. Compounds 22, 23, 27-29, 47 and 48 showed satisfactory levels of potency (pIC(50) > 5), which in one case (compound 23) reached a really interesting value (pIC(50) 6.92). Furthermore, for some selected compounds (19, 22, 23, 26, 28, 29, 47), the vasorelaxing activity was also evaluated in the presence of the guanylate cyclase blocker ODQ or of the adenylate cyclase blocker SQ 22536, and some of these can be considered as possible guanylate-cyclase inhibitors. Finally, compounds 19, 22 and 23 were also tested in the presence of the ATP-sensitive potassium channel blocker glybenclamide and seem to possess activating properties on these potassium channels. (C) 2001 Editions scientifiques et medicales Elsevier SAS.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
