Synthesis and smooth muscle relaxant activity of a new series of potassium channel activators: 3-amido-1,1-dimethylindan-2-ols.
The synthesis of a novel series of smooth muscle relaxants which have been shown to act via the opening or activation of potassium channels is described. Compounds have been evaluated for their ability to inhibit spontaneous tone in guinea pig isolated trachealis and structure-activity relationships are discussed. One compound in particular, 1,1-dimethyl-5-nitro-3-(2-pyridon-1-yl)indan-2-ol, (16) was identified as a potent relaxant of airways smooth muscle in vitro with IC50 = 0.15 microM and was found to significantly inhibit histamine-induced dyspnoea in conscious guinea pigs when given orally 30-45 min prior to challenge.
Buckle
D R
DR
SmithKline Beecham Pharmaceuticals, Biosciences Research Centre, Epsom, Surrey, England.
Arch
J R
JR
Edge
C
C
Foster
K A
KA
Houge-Frydrych
C S
CS
Pinto
I L
IL
Smith
D G
DG
Taylor
J F
JF
Taylor
S G
SG
Tedder
J M
JM
D000577:Amides / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects / Q000502:physiology; D001993:Bronchodilator Agents; D055598:Chemical Phenomena; D002621:Chemistry; D019806:Cromakalim; D006168:Guinea Pigs; D007189:Indans / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D015394:Molecular Structure; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D010276:Parasympatholytics / Q000138:chemical synthesis* / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D011758:Pyrroles / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014132:Trachea / Q000187:drug effects / Q000502:physiology
D000577:Amides; D001578:Benzopyrans; D001993:Bronchodilator Agents; D007189:Indans; D010276:Parasympatholytics; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; C067816:1,1-dimethyl-5-nitro-3-(2-pyridon-1-yl)indan-2-ol