Potassium channel activators based on the benzopyran substructure: synthesis and activity of the C-8 substituent.
The synthesis of a series of methoxy bearing 2,2-dimethyl-2H-1-benzopyrans have been achieved for testing as potassium channel activators. The synthesis involves formation of 6-cyano-8-methoxy-2,2-dimethyl-2H-1-benzopyran from vanillin, epoxidation, then ring opening of the epoxide with nitrogen nucleophiles to produce the new benzopyrans. Biological testing showed a dramatic decrease in activity thus revealing an important site of activity in this class of compounds.
Thompson
Rona
R
School of Chemical and Physical Sciences, Victoria University of Wellington, Box 600, Wellington, New Zealand.
Doggrell
Sheila
S
Hoberg
John O
JO
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D019806:Cromakalim / Q000494:pharmacology; D004852:Epoxy Compounds / Q000737:chemistry; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D020110:Pinacidil / Q000494:pharmacology; D011169:Portal Vein / Q000187:drug effects / Q000502:physiology; D015221:Potassium Channels / Q000819:agonists*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D001578:Benzopyrans; D004852:Epoxy Compounds; D015221:Potassium Channels; D019806:Cromakalim; D020110:Pinacidil