Relaxant activity of 6-cyano-2,2-dimethyl-2H-1-benzopyran-4-carboxamides and -thiocarboxamides and their analogues in guinea pig trachealis.
Structural modifications of the potassium channel activator cromakalim (1) are described in which the amide moiety at C-4 has been replaced by carboxamide and thiocarboxamide functions. Analogues in which the hydroxyl group at C-3 has been oxidized or removed are also disclosed. Such analogues display an interesting profile of smooth muscle relaxant activity in the guinea pig isolated trachea, not all of which appears to result from the opening of potassium channels, but few compounds retain useful in vivo activity. However, one compound in particular, 6-cyano-2,2-dimethyl-N-methyl-2H-1-benzopyran-4-thiocarboxamide (13) was shown to be a potent potassium channel activator in vitro and to provide prolonged protection to guinea pigs from the respiratory effects of inhaled histamine.
Arch
J R
JR
SmithKline Beecham Pharmaceuticals, Biosciences Research Centre, Surrey, England.
Buckle
D R
DR
Carey
C
C
Parr-Dobrzanski
H
H
Faller
A
A
Foster
K A
KA
Houge-Frydrych
C S
CS
Pinto
I L
IL
Smith
D G
DG
Taylor
S G
SG
D000818:Animals; D001578:Benzopyrans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001993:Bronchodilator Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D019806:Cromakalim; D006168:Guinea Pigs; D008297:Male; D015394:Molecular Structure; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011758:Pyrroles / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013854:Thioamides / Q000138:chemical synthesis / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D001578:Benzopyrans; D001993:Bronchodilator Agents; D015221:Potassium Channels; D011758:Pyrroles; D013854:Thioamides; D019806:Cromakalim; C070496:6-cyano-2,2-dimethyl-N-methyl-2H-1-benzopyran-4-thiocarboxamide