G. Biagi et al., 5-(4 '-substituted-2 '-nitroanilino)-1,2,3-triazoles as new potential potassium channel activators. I, EUR J MED C, 35(7-8), 2000, pp. 715-720
By the hypothesised correlation with the large conductance Ca++-activated p
otassium channel (BKCa) openers NS 004 and NS 1619, bearing a benzimidazolo
ne ring, a series of new 5-(4'-substituted-2'-nitroanilino)-1,2,3-triazoles
were synthesised and tested on in vitro isolated vascular preparation. The
compounds were prepared. starting from the appropriately substituted 2-nit
ro-phenylazides by 1,3-dipolar cycloaddition reaction to cyanoacetamide and
following Dimroth isomerisation of the corresponding 1-arylsubstituted-5-a
mino-1,2,3-triazoles. The analogous 5-(4'-substituted-2'-amino-anilino)-1,2
,3-triazoles were also prepared to assess the role of the nitro group in th
e pharmacophoric model. Almost all the nitro compounds showed a vasorelaxan
t activity on endothelium-denuded rat aortic rings with a potency comparabl
e to that recorded for the reference compound NS 1619. Such a vasorelaxing
activity was significantly reduced by the increase of the level of membrane
depolarisation and by the potassium channel blocker 4-aminopyridine with a
pharmacodynamic behaviour consistent with a potassium channel activation.
(C) 2000 Editions scientifiques et medicales Elsevier SAS.