Cloxacepride and related compounds: A new series of orally active antiallergic compounds

Article abstract of DOI:10.1021/jm00361a022

4-[(p-Chlorophenoxy)acetyllamino]-5-chloro-2-methoxy-N-[2-(diethylamino)ethyl]benzamide (cloxacepride) exhibited substantial oral antiallergic potential in a reaginic PCA test in rats over a wide range of antigenic challenge times. Available reference compounds with oral activity, such as doxantrazole and 7-(2-hydroxyethoxy)-9-oxo-xanthene-2-carboxylic acid (AH 7725, 4) were active only when administered 15 min before challenge: 4, in particular, was not consistent in effect. Oral ED₅₀ values for cloxacepride of 46-49 mg/kg were comparable to that of theophylline and to an intravenous injection of 2 mg/kg of disodium chromoglycate (DSCG) followed by immediate challenge. Following oral ED₅₀ doses, 1 showed slower onset and longer duration of action than theophylline. The absence of inhibition of systemic anaphylaxis and of antihistaminic activity suggests specific effect for reaginic antigen antibody reactions. Structure-activity relationships of various chemical modifications were investigated and discussed in terms of essential substituents.