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.
Biagi
G
G
Dipartimento di Scienze Farmaceutiche, Università di Pisa, Italy.
Calderone
V
V
Giorgi
I
I
Livi
O
O
Scartoni
V
V
Baragatti
B
B
Martinotti
E
E
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D015394:Molecular Structure; D015221:Potassium Channels / Q000819:agonists*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D007093:Imidazoles; D015221:Potassium Channels; D014230:Triazoles; D014665:Vasodilator Agents