title: 1,2,3-Triazol-carboxanilides and 1,2,3-triazol-(N-benzyl)-carboxamides as BK-potassium channel activators. XII.
abstract: The chemical structures of many synthetic activators of large-conductance calcium-activated potassium channels (BK channels) satisfy a simple pharmacophore model, consisting of two appropriately substituted phenyl rings connected by a linker of a heterogeneous nature. In this paper, a series of new compounds with modifications of the linker portion of the above pharmacophore are described. In particular, in these new derivatives, the linker portion is represented by a 1,2,3-triazole-carboxamide group, which can be viewed as a combination of two different kinds of linker, independently used in previous series of BK-openers: the amide function and the 1,2,3-triazole ring. The overall finding of this study indicated that the triazole-carboxamide derivatives were generally poorly effective and that this structural modification of the linker is deleterious for activity on BK channels. Therefore, it can be hypothesized that the increase of the steric hindrance of the linker and/or the increase of the distance between the two aromatic portions are negative for the interaction with the biological target.
authors.affiliation: Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, Università di Pisa, via Bonanno 6, I-56126 Pisa, Italy. calderone@farm.unipi.it
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Calderone
authors.forename: Francesca Lidia
authors.initials: FL
authors.lastname: Fiamingo
authors.forename: Gabriella
authors.initials: G
authors.lastname: Amato
authors.forename: Irene
authors.initials: I
authors.lastname: Giorgi
authors.forename: Oreste
authors.initials: O
authors.lastname: Livi
authors.forename: Alma
authors.initials: A
authors.lastname: Martelli
authors.forename: Enrica
authors.initials: E
authors.lastname: Martinotti
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000813:Anilides / Q000737:chemistry*; D000818:Animals; D001393:Azoles / Q000737:chemistry*; D008297:Male; D015394:Molecular Structure; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
chemical_list: D000480:Alkynes; D000577:Amides; D000813:Anilides; D001393:Azoles; D015221:Potassium Channels