Antigen challenge of actively sensitized guinea pigs results in the release of histamine eicosanoids (products of the cyclooxygenase pathway of arachidonic acid metabolism) and slow reducing substance of anaphylaxis (SRS-A). By antagonizing the effects of histamine, serotonin, and acetylcholine, inhibiting the cyclooxygenase pathway and supplying arachidonic acid as substrate, the contribution of SRS-A to anaphylactic bronchospasm can be enhanced, thus allowing suitable quantitation of antagonists. This SRS-A mediated bronchospasm can be inhibited in a dose dependent fashion by FPL55712, a selective antagonist of SRS-A. This system represents an in vivo method capable of detecting compounds which inhibit SRS-A synthesis/release of SRS-A action at the effector organ.

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2-(Diethylamino)-6-nitrobenzonitrile (72). To a mixture of 3.82 g (0.02 mol) of 2-(ethylamino)-6-nitrobenzonitrile (73) and 3.2 g (0.02 mol) of ethyl iodide in 100 mL of DMF was added 0.96 g (0.02 mol) of 50% NaH (in oil) in portions. The mildly exothermic reaction was stirred for 10 min, poured into ice-water, and extracted into methylene chloride. Evaporation gave an oil that was passed through a short column of silica gel (20 g) with methylene chloride. The bright orange oil was collected and triturated with hexane to give 3.1 g of pure product, mp 39-41 °C.2-Nitro-5-(dimethylamino)benzoic Acid (75). Sodium cyanoborohydride (57 g) was added to a mixture of 54.6 g (0.21 mol) of commercial (70%) 2-nitro-5-aminobenzoic acid and 240 mL of formalin in 1200 mL of acetonitrile. The reaction mixture was stirred overnight and evaporated to one-third volume. The product crystallized as the hemihydrate: mp 187-189 °C; yield 50 g (100%). Anal. (C9H10N2O4-0.5H2O) C, , N. 5-(Dimethylamino)anthranilic Acid (76). A mixture of 10.5 g (0.05 mol) of the nitrobenzoic acid 75,5 g of 10% Pd on charcoal, and 25 g (0.3 mol) of cyclohexene in 200 mL of ethanol was heated at reflux for 3 h. The hot reaction mixture was filtered through Celite, the Celite pad was extracted three times with hot ethanol, and the combined ethanol filtrates were evaporated to one-third volume. Water was added to cloudiness, whereupon the pure product crystallized: yield 8.0 g (93%); mp 234-238 °C (lit.28 234-236 °C).

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