PRD-92-Ea [5,5-Dimethyl-11-oxo-5H, HH-(2) benzopyrano (4,3-g) (1) benzopyran-9-carboxylic acid ethanolamine], was an active antiallergic compound in rat and monkey experimental models of immediate hypersensitivity. It inhibited, in a dose-dependent manner, the rat PCA reaction after both intravenous and oral administration. It also inhibited the degranulation of rat peritoneal mast cells after antigenic challenge. PRD-92-Ea was also active in preventing bronchoconstriction in Ascaris-sensitive Rhesus monkeys after intravenous, topical and oral administration. Using chopped monkey tissues, it was found that PRD-92-Ea prevented histamine release from the respiratory mast cells, but not from the cutaneous mast cells. No reason for this dichotomy of effect is known. PRD-92-Ea showed antagonistic activity against the allergic mediators released from mast cells. In order of decreasing potency it was active against SRS-A (monkey lung), PGF_2α, PGE₂, serotonin, bradykinin and histamine. Apart from its antiallergic effects PRD-92-Ea had no other significant pharmacological activity.

DSCG and PRD-92-Ea showed tachyphylaxis in the rat PCA test when a large intravenous dose (40 mg/kg of DSCG and 20 mg/kg of PRD-92-Ea) was given 30 min before administering intravenously the expected effective doses at the time of antigen challenge. This predosing led to a marked loss of effectiveness. Cross-reacting tachyphylaxis was also demonstrated in this model. Predosing rats with DSCG led to a great loss of effectiveness of a subsequent expected active dose of PRD-92-Ea and predosing with PRD-92-Ea had the same effect in preventing the antiallergic action of a subsequent dose of DSCG. The Rhesus monkey (Macaca mulatto) did not exhibit this phenomenon of tachyphylaxis. PRD-92-Ea and DSCG were given intravenously 30 min before and the same dose of 20 mg/kg repeated just before Ascaris suum challenge in the Rhesus monkey asthma model with no loss of their expected effectiveness.

The synthesis and properties of the title compounds 1 are described. Many of these compounds are potent inhibitors of the passive cutaneous anaphylaxis reaction of rats against egg albumin challenge. Structural variations include substitutions in the 2, 3, 4, 5, 7, and 12 position of the nucleus 1. A novel rearrangement from a compound of the related [3,4-f] series to this group is reported.

The synthesis and properties of the title compounds 1 are described. Several of these compounds, in addition to being potent inhibitors of the passive cutaneous anaphylaxis reaction of rats against egg albumin challenge, significantly block the effects of several mediators of anaphylaxis in isolated smooth muscle preparations. An improved procedure for the isolation and partial purification of SRS-A from chopped guinea pig lung tissue is also described.

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