NEW ANTIALLERGIC PYRANO[3,2-G]QUINOLINE-2,8-DICARBOXYLIC ACIDS WITH POTENTIAL FOR THE TOPICAL TREATMENT OF ASTHMA

A number of antiallergic pyranoquinolinedicarboxylic acid derivatives with potential for the topical treatment of asthma have been synthesized. All the compounds have been evaluated against rat passive cutaneous anaphylaxis and in a dog hypotension screen. This is the first detailed description of the application of the latter screen for the identification of antiallergic agents. Two compounds, disodium 9-ethyl-6,9-dihydro-4,6-dioxo-10-propyl-4H-pyrano[3,2-g]quinoline-2,8-dicarboxylate (86) and disodium 6-(methylamino)-4-oxo-10-propyl-4H-pyrano[3,2-g]quinoline-2,8-dicarboxylate (72), were selected and further evaluated for their ability to induce phosphorylation of a 78000 molecular weight protein associated with the rat peritoneal mast cell. Their ability to inhibit histamine release from these cells and from a mucosal mast cell preparation has also been evaluated. These compounds, nedocromil sodium (TILADE 86) and minocromil (the free acid of 72), are at present undergoing therapeutic evaluation. The rationale for the screening procedure and the relevance of the second carboxylic acid function of these dibasic acids to receptor binding are discussed.