Arylacethydroxamic Acids: a New Class of Potent Non-steroid Anti-inflammatory and Analgesic Substances

Abstract

IN recent years much effort has been directed to the search for non-steroid anti-inflammatory substances which can be used in the therapy of rheumatic diseases and related conditions¹. This communication reports the finding that a chemical family hitherto unexplored in this respect, namely, the arylacethydroxamic acids, includes several substances endowed with considerable anti-inflammatory and analgesic properties, and also a remarkably low degree of toxicity. A particularly interesting compound in this series was 4-butoxy-3-methyl-phenylacethydroxamic acid (I). In a comparative investigation with known antiphlogistic compounds, using the Benitz and Hall carrageenin-induced abscess test in rats², compound (I), in exactly the same dose, proved only slightly less active (c. half) than phenylbutazone (l,2-diphenyl-3,5-diketo-4-butylpyrazolidine), definitely more active than ‘Ibufenac’ (p-isobutylphenylacetic acid), and considerably more so than aspirin. The activity shown by compound (I) at the high dosage of 1 g/kg was as intense as that of the maximum tolerated dose of phenylbutazone (400 mg/kg) and considerably more so than that (10 mg/kg) of ‘Indomethacin’ (1-p-chlorobenzoyl-5-methoxyindolyl-3-acetic acid), which is the most efficient non-steroid antiphlogistic substance known so far. Compound (I) was also strongly active in the carrageenin-induced granuloma test in rats, whereas phenylbutazone and aspirin are known to behave poorly in this type of assay³.