Variation in the aromatic ring of cromakalim: antihypertensive activity of pyranopyridines and 6-alkyl-2H-1-benzopyrans.
The synthesis and antihypertensive activity in the spontaneously hypertensive rat of two new series of analogues related to cromakalim (1) are described. In the first series, where the benzopyran nucleus has been replaced by a pyranopyridine nucleus, the position of the nitrogen atom has been found to be critical for activity, and the most potent compounds are the pyrano[3,2-c]pyridines. In the second series, where the powerful electron-withdrawing cyano group of compound 1 has been replaced by alkyl and phenyl groups, the order of antihypertensive potency is ethyl, isopropyl, tert-butyl greater than propyl, cyclopentyl greater than methyl greater than phenyl.
Burrell
G
G
SmithKline Beecham Pharmaceuticals, Medicinal Research Centre, Harlow, Essex, England.
Cassidy
F
F
Evans
J M
JM
Lightowler
D
D
Stemp
G
G
D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry* / Q000627:therapeutic use; D055598:Chemical Phenomena; D002621:Chemistry; D019806:Cromakalim; D006973:Hypertension / Q000188:drug therapy; D011714:Pyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D011758:Pyrroles / Q000737:chemistry* / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR; D013329:Structure-Activity Relationship
D000959:Antihypertensive Agents; D001578:Benzopyrans; D011714:Pyrans; D011725:Pyridines; D011758:Pyrroles; D019806:Cromakalim