Biagi G, Calderone V, Giorgi I, Livi O, Scartoni V, Baragatti B, Martinotti E
Dipartimento di Scienze Farmaceutiche, Università degli Studi di Pisa, via Bonanno 6, 56126, Pisa, Italy.
Eur J Med Chem. 2000 Jul-Aug;35(7-8):715-20. doi: 10.1016/s0223-5234(00)00180-x.
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.
通过与带有苯并咪唑酮环的大电导钙（++）激活钾通道（BK（Ca））开放剂NS 004和NS 1619的假设相关性，合成了一系列新的5-（4'-取代-2'-硝基苯胺基）-1,2,3-三唑，并在体外分离的血管制剂上进行了测试。这些化合物从适当取代的2-硝基苯叠氮化物开始，通过与氰基乙酰胺的1,3-偶极环加成反应以及相应的1-芳基取代-5-氨基-1,2,3-三唑的迪姆罗特异构化反应制备。还制备了类似的5-（4'-取代-2'-氨基苯胺基）-1,2,3-三唑，以评估硝基在药效团模型中的作用。几乎所有的硝基化合物对去内皮的大鼠主动脉环都表现出血管舒张活性，其效力与参考化合物NS 1619相当。随着膜去极化水平的增加和钾通道阻滞剂4-氨基吡啶的作用，这种血管舒张活性显著降低，其药效学行为与钾通道激活一致。
