5-(4 '-substituted-2 '-nitroanilino)-1,2,3-triazoles as new potential potassium channel activators. I

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.