| 10960187 |
Biagi G, Calderone V, Giorgi I, Livi O, Scartoni V, Baragatti B, Martinotti E: 5-(4'-Substituted-2'-nitroanilino)-1,2,3-triazoles as new potential potassium channel activators. Eur J Med Chem. 2000 Jul-Aug;35(7-8):715-20.
I.. By the hypothesised correlation with the large conductance Ca (++)-activated potassium channel (BK (Ca)) openers NS 004 and NS 1619, bearing a benzimidazolone 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-nitro-phenylazides by 1,3-dipolar cycloaddition reaction to cyanoacetamide and following Dimroth isomerisation of the corresponding 1-arylsubstituted-5-amino-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 the pharmacophoric model. Almost all the nitro compounds showed a vasorelaxant activity on endothelium-denuded rat aortic rings with a potency comparable 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. |
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