Relaxant activity of 6-cyano-2,2-dimethyl-2H-1-benzopyran-4-carboxamides and -thiocarboxamides and their analogs in guinea pig trachealis

Authors:
  • DBDerek R. Buckle
    Derek R. Buckle
  • CCClaire Carey
    Claire Carey
  • HPHilary Parr-Dobrzanski
    Hilary Parr-Dobrzanski
  • AFAndrew Faller
    Andrew Faller
  • KFKeith A. Foster
    Keith A. Foster
  • CHCatherine S. V. Houge-Frydrych
    Catherine S. V. Houge-Frydrych
  • IPIvan L. Pinto
    Ivan L. Pinto
  • DSDavid G. Smith
    David G. Smith
  • STStephen G. Taylor
    Stephen G. Taylor
Publisher website
Google Scholar
Abstract
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modifications of the potassium channel activator cromakalim (1) are described in which the amide moiety at C-4 has been replaced by carboxamide and thiocarboxamide functions.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.