The synthesis and antiallergic activity of a series of 2-hydroxy-N-1H-tetrazol-5-ylbenzamides and isomeric N-(2-hydroxyphenyl)-1H-tetrazole-5-carboxamides is described. A relationship between structure and intravenous antiallergic activity in the rat passive cutaneous anaphylaxis (PCA) test has been established using a Hansch/Free-Wilson model and used to direct studies toward potent derivatives. The contribution of physicochemical properties to activity is discussed. One member of this series, N-(3-acetyl-5-fluoro-2-hydroxyphenyl)-1H-tetrazole-5-carboxamide (3f), which was selected for further evaluation, has an ID50 value of 0.16 mg/kg po and is 130 times more potent than disodium cromoglycate (DSCG) on intravenous administration.

Summary Human lung tissue, passively sensitized with reaginic antibodies, released prostaglandins E1, E2 and F2α in addition to histamine and slow reacting substance (SRS‐A), when exposed to the appropriate antigen. No rabbit aorta contracting substance (RCS) was detected. Experiments with rats and guinea‐pigs showed that the release of RCS is not confined to anaphylactic reactions mediated by non‐reaginic antibodies but may be a feature of anaphylaxis in guinea‐pigs alone. Human lung tissue gently agitated with a blunt nylon rod liberated an E‐type prostaglandin and RCS in addition to histamine and SRS‐A. Human isolated bronchial muscle was contracted by RCS. Disodium cromoglycate antagonized the release of prostaglandins during anaphylaxis but not during agitation of human lung tissue, whereas indomethacin blocked the release of prostaglandins during agitation and anaphylaxis. The release of an E‐type prostaglandin during anaphylaxis in human lung tissue, which inhibits the further release of histamine could be another example of the regulatory role of prostaglandins in body functions.

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5‐Aminotetrazol (I) wird mit den substituierten Salicylsäuren (II) zu den Amiden (III) umgesetzt.