Antiallergic properties of SQ 13,847, an orally effective agent. I. Activity in vivo.

A structurally novel pyrazolo[1,5-c]quinazoline, SQ 13,847, was demonstrated to be an orally active antiallergic agent. The compound inhibited immunoglobulin (Ig)E-mediated passive cutaneous anaphylaxis (PCA) and passive pulmonary anaphylaxis in the rat (ID50 = 2 to 4 mg/kg p.o.), but failed to affect IgG-mediated PCA in the rat, IgE-mediated PCA in the mouse or IgG1-mediated PCA in the guinea pig. The relative potencies of SQ 13,847 and its 2-carboxylic acid metabolite, SQ 12,903, upon oral vs. intravenous administration were consistent with a role of SQ 13,847 as an orally absorbed prodrug of SQ 12,903. In the rat, SQ 13,847 is not an antagonist of histamine in serotonin, in beta adrenergic agonist or a bronchodilator.