Some structural changes on triazolyl-benzotriazoles and triazolyl-benzimidazolones as potential potassium channel activators. III

This paper reports the synthesis and pharmacological evaluation of some compounds, obtained by structural modifications of 1,2,3-triazolyl-benzotriazoles and 1,2,3-triazolyl-benzimidazolones, which had shown activity as potential activators of the big-conductance calcium-activated potassium channels (BK Ca). Changes have concerned the introduction of a hinderer substituent in the 5-position of the benzimidazolone ( 4a, b) and benzotriazole ( 5a, b) rings, opening of the benzimidazolone ring ( 7) and substitution of the 1,2,3-triazole ring with a 2-hydroxyphenyl ring ( 10). Furthermore a series of 3-aryl-benzotriazin-4-one derivatives ( 13a– e) has been studied, which appears as a modification and/or combination of the benzimidazolone and benzotriazole rings. Only compound 10 shows interesting activity, while the other structural modifications either do not increase (compounds 4 and 5) or reduce (compounds 7 and 13) the pharmacological activity. However, these results provide useful information about structure–activity relationships.