Novel 1,4-benzothiazine derivatives as large conductance Ca2+-activated potassium channel openers.
The design and synthesis of a novel class of 1,4-benzothiazines targeted for the large-conductance calcium-activated potassium channels (BK) are presented. In vitro functional characterization of BK channel opening activity was assessed by measuring the relaxation of isolated rat aortic rings precontracted with KCl 20 mM. The results of this study show that the 1,4-benzothiazine heterocyclic nucleus is a suitable backbone for designing novel BK-openers; indeed, some of these new 1,4-benzothiazine derivatives had a vasorelaxant potency comparable or superior to that of reference BK-activator NS-1619 (1).
Calderone
Vincenzo
V
Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, Università degli Studi di Pisa, Via Bonanno 6, 56126 Pisa, Italy.
Spogli
Roberto
R
Martelli
Alma
A
Manfroni
Giuseppe
G
Testai
Lara
L
Sabatini
Stefano
S
Tabarrini
Oriana
O
Cecchetti
Violetta
V
D000818:Animals; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013843:Thiazines / Q000138:chemical synthesis / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
C446962:1,4-benzothiazine; D051036:Large-Conductance Calcium-Activated Potassium Channels; D013843:Thiazines