Pyranenamines: a new series of antiallergic compounds

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Abstract
Condensation of 3,5-diacylpyrantriones with various aromatic amines gave a new class of potent, orally active, antiallergic compounds, the 3-[(arylamino)ehtylidene]-5-acylpyrantriones (pyranenamines) as evaluated in the traditional rat passive cutaneous anaphylaxis (PCA) assay and in the in vitro fragmented rat and primate lung assay. Potencies in the PCA system, when measured i.v., reached a maximum ID50 [dose producing 50% inhibition] of 0.9 .mu.g/kg (1000 times more potent than disodium chromoglycate) with 5-acetyl-4-hydroxy-3-[1-[(3,5-bis-glyceramoylphenyl)amino]ethylidene]-2H-pyran-2,6(3H)-dione as predicted by structure-activity relationship (SAR) analyses. Potencies in the i.v. PCA system correlated with potencies in the in vitro rat lung system but not with potencies in the oral PCA system or the in vitro primate lung system. Several compounds had good oral potency and 1 analog, 3-acetyl-4-hydroxy-3-[1-[3-amino-4-hydroxyphenyl)amino]ethylidene]-2H-pyran-2,6(3H)-dione hydrochloride reached an oral ID50 of less than 1 mg/kg and was more than 10 times more effective than disodium chromoglycate at inhibiting the release of histamine and slow-reacting substance of anaphylaxis in the fragmented primate lung assay.

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