title: Some structural changes on triazolyl-benzotriazoles and triazolyl-benzimidazolones as potential potassium channel activators. III.
abstract: 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.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Pisa, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Biagi
authors.forename: V
authors.initials: V
authors.lastname: Calderone
authors.forename: I
authors.initials: I
authors.lastname: Giorgi
authors.forename: O
authors.initials: O
authors.lastname: Livi
authors.forename: V
authors.initials: V
authors.lastname: Scartoni
authors.forename: B
authors.initials: B
authors.lastname: Baragatti
authors.forename: E
authors.initials: E
authors.lastname: Martinotti
mesh_terms: 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
chemical_list: D007093:Imidazoles; D015221:Potassium Channels; D014230:Triazoles; D014665:Vasodilator Agents