Aminophenol Derivatives Research Articles

Inhibition of prostaglandin synthetases derived from neuronal and glial cells and rat renal medulla by ortho-, meta- and para-substituted aminophenolic compounds

Acetophenetidines, acetamidophenols, phenetidines and aminophenols substituted in o-, m- or p-position inhibit prostaglandin-synthetases originating from C 1300 mouse neuroblastoma cells (clone N2A), rat astrocytoma cells (clone C 6) and rat renal medulla. Desacetylated compounds were more potent inhibitors than their corresponding acetyl derivatives and many o- and m-analogues were more active than p-substituted structures like paracetamol (p-acetamidophenol) or phenacetin (p-acetophenetidine). When twelve o-, m- or p-aminophenolic test compounds were compared to acetylsalicylic acid and indomethacin, o-, and p-phenetidine and o-aminophenol were as effective as acetylsalicylic acid. All aminophenol derivatives which inhibited prostaglandin synthesis suppressed cultured nervous cell and kidney cyclo-oxygenases to similar extents. Our results suggest that aminophenolic drugs are not more effective against pros taglandin-synthetases in the CNS than against those in the periphery.

Decreasing inhibitory potency of prostaglandin synthetase inhibitors during their cooxidative metabolism. Studies on aminophenols, pyrazolon derivatives and 1,3-diphenylisobenzofuran.

A variety of prostaglandin synthetase inhibitors are cooxygenated during arachidonic acid peroxidation catalyzed by rat renal medulla prostaglandin synthetase or soybean lipoxygenase. Phenylbutazone, aminopyrine, 1,3-diphenylisobenzofuran, paracetamol, p-aminophenol, p-phenetidine and other o- and m-substituted aminophenol derivatives were cooxygenated, whereby prostaglandin synthetase inhibition was significantly weakened due to the formation of less inhibitory metabolites. In contrast, the inhibitory potency of diclofenac, indomethacin and phenacetin and its analogues remained unchanged during prostaglandin synthesis inhibition, because these compounds were no suitable cooxygenation substrates. Evidence is given that quinone imines may not be involved in the cooxidative metabolism of paracetamol and other aminophenols. As to the mechanisms of cooxygenation of suitable substrates dependent on their chemical structures either the arachidonic acid oxygenase or the subsequent hydroperoxidase reaction may trigger the oxygenation. 1,3-Diphenylisobenzofuran is metabolized during the formation of arachidonic acid hydroperoxides in contrast to paracetamol, which requires an additional peroxidase reaction to yield reactive metabolites.

Reduction of nitrotyrosyl residues in proteins

Reduction of nitrotyrosine and nitrotyrosyl peptides largely proceeds to the formation of the aminophenol derivative. However, a small amount of an acidic component has been detected in the reaction which has been tentatively identified as an aminosulfonic acid derivative of tyrosine.

Dipheyl Etherを基核とするAcid Hydrazide誘導体の合成研究 (第12報)

Hydrazinolysis with hydrazine hydrate was examined with mononitro-monoamino-diphenyl ethers possessing one each nitro and amino group in each benzene ring. In compounds with nitro group in the position ortho to phenoxyl group, hydrazine hydrate effected cleavage of ether oxygen to form o-nitrophenylhydrazine (II) and the corresponding aminophenol derivative (III). (II) easily underwent dehydration to form 1-hydroxybenzotriazole (IIa).In compounds with the nitro group meta to phenoxyl group, (IV) resisted hydrazinolysis, either at ordinary or higher pressure, and only reduction of the nitro group occured to produce a diamino derivative (V). In the case of compounds with a nitro group para to phenoxyl group, (VI) resisted hydrazinolysis at ordinary pressure but submitted to hydrazinolysis at higher pressure to form p-nitrophenylhydrazine (VII) and the corresponding aminophenol derivative (VIII), with a minute amount of the reduction product as diamino derivative (IX). Under some reaction conditions, the substance (VIII) further underwent autoreduction to form nitroaniline (VIIb) and nitrobenzene (VIIa).