Synthesis and antihypertensive activity of 4-(substituted-carbonylamino)-2H-1-benzopyrans.
The synthesis and antihypertensive activity of a series of novel 4-(substituted-carbonylamino)-2H-1-benzopyran-3-ols, administered orally to conscious spontaneously hypertensive rats, are described. Optimum activity was observed for compounds with alkyl, amino, or aryl groups flanking the carbonyl group. Of the alkyl and amino series the most potent compounds contained the methyl and methylamino groups, respectively. Several analogues have been compared with cromakalim (1) for their effects on potassium ion efflux in the rabbit mesenteric artery using rubidium-86 as a marker. The ability of each compound to enhance rubidium-86 efflux is approximately parallelled by its blood pressure lowering activity, and thus these analogues, like compound (1), belong to the series of drugs which have been classified as potassium-channel activators.
Ashwood
V A
VA
SmithKline Beecham Pharmaceuticals, Medicinal Research Centre, Harlow, Essex, England.
Cassidy
F
F
Coldwell
M C
MC
Evans
J M
JM
Hamilton
T C
TC
Howlett
D R
DR
Smith
D M
DM
Stemp
G
G
D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011918:Rats, Inbred SHR; D013329:Structure-Activity Relationship
D000959:Antihypertensive Agents; D001578:Benzopyrans; D011188:Potassium