The individual enantiomers of cis-cromakalim possess K+ channel opening activity

摘要: Abstract Cromakalim (BRL 34915), a racemic trans-3,4-disubstituted benzopyran, is the prototype of novel group vasorelaxants which act by opening K+ channels in cell membrane, channel openers. The enantiomers cis-cromakalim were synthesized and their biological activity compared to that (trans-)cromakalim. Both (+)-(3R,4R) its (−)-(3S,4S) antipode inhibited binding opener [3H]P1075 strips rat aorta with pKi values 5.4 5.2, respectively. They relaxed noradrenaline-induced contractions isolated under control conditions pD2 5.7 5.2; vasorelaxant potency was greatly diminished depolarized (KCl = 55 mmol/l). compounds increased permeability membrane for as suggested ability stimulate 86Rb+ efflux from aortic strips. efflux-stimulating effects sulfonylurea, glibenclamide. These results show are genuine (R,R) enaniomer 50 times weaker than (−)-(3S,4R) enantiomer cromakalim ( levcromakalim, BRL 38227) but 3 more potent (+)-(3R,4S) enaniomer. data highlight importance stereochemistry at both 4 position benzopyran ring.