New amido derivatives as potential BKCa potassium channel activators. XI.
The vasorelaxing effects of exogenous activators of large-conductance calcium-activated potassium channels (BK channels) can furnish the pharmacological rational basis for the treatment of hypertension and/or other diseases related with an impaired contractility of vessels. Since in previous works some benzanilide derivatives showed BK channel-induced vasorelaxing activity, in this paper we have taken into consideration the introduction of methylene spacer(s) between the amide linker and one or both the aromatic substituents, to evaluate the pharmacological effect caused by these lengthenings and to obtain possible useful information about structure-activity relationships. Overall, the main findings of this work suggest that the introduction of one or two methylene group(s) in the amide linker exerts a negative influence on the BK-opening properties, which can be due to an excessive lengthening of the spacer between the two aromatic rings and/or to further degrees of conformational freedom.
Calderone
Vincenzo
V
Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, Università di Pisa, via Bonanno 6, I-56126 Pisa, Italy. calderone@farm.unipi.it
Fiamingo
Francesca Lidia
FL
Amato
Gabriella
G
Giorgi
Irene
I
Livi
Oreste
O
Martelli
Alma
A
Martinotti
Enrica
E
D000813:Anilides / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D015640:Ion Channel Gating; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000819:agonists*; D008958:Models, Molecular; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000737:chemistry / Q000494:pharmacology
D000813:Anilides; D051036:Large-Conductance Calcium-Activated Potassium Channels; D014665:Vasodilator Agents; C034595:benzanilide