CYANOAMIDINES .1. SYNTHESIS AND VASODILATORY ACTIVITY OF N-SUBSTITUTED HETEROAROMATIC CYANOAMIDINES

Various heteroaromatic cyanoamidines were synthesized starting from ni triles via cyanoimidates or from amides via thioamides. The compounds were tested for inhibitory effect on the 40 mM K+-induced contraction of rat aorta strips and selected compounds were also evaluated for ant agonism of the norepinephrine-induced contraction. Most of the cyanoam idines showed vasodilatory activities. Potent vasoactive compounds wer e also examined for stimulation of the Rb-86(+) efflux to determine th eir potassium channel opening actions. Maximum potency was displayed b y -cyano-N'-(2-nitroxyethyl)-3-pyridinecarboxamidine (3h). The methane sulfonate of 3h, which was designated as KRN2391, has been selected fo r further development as an antianginal agent.