| abstract |
The present invention provides substituted 11-phenyl-dibenzazepine compounds, as well as analogues thereof, which are specific, potent and safe inhibitors of the Ca2+-activated potassium channel (Gardos channel) of erythrocytes, of mammalian cell proliferation and/or of secretagogue-stimulated transepithelial electrogenic chloride secretion in intestinal cells. The compounds can be used to reduce sickle erythrocyte dehydration and/or delay the occurrence of erythrocyte sickling or deformation in situ as a therapeutic approach towards the treatment or prevention of sickle cell disease. The compounds can also be used to inhibit mammalian cell proliferation in situ as a therapeutic approach towards the treatment or prevention of diseases characterized by abnormal cell proliferation. Furthermore, the compounds can also be used to inhibit chloride secretion in intestinal cells as a therapeutic approach towards the treatment of diarrhea and scours. |