Studies on the Syntheses of Analgesics. LIII. Synthesis of 3-(4-Substituted phenyl)-2-oxobutanamide Derivatives (Studies on the Syntheses of Heterocyclic Compounds. DCCCXLV)

Abstract

Derivatives of 3-[4-(1, 3-dihydro-1-oxo-2H-isoindol-2-yl) phenyl]-2-oxobutanamide (1), exhibiting potent anti-inflammatory and analgesic activity, were obtained from 3-(4-aminophenyl)-2-oxo-butanamide (2) and 3-[4-(1, 3-dihydro-1-oxo-2H-isoindol-2-yl) phenyl]-2-oxobutanoic acid (25) as intermediates. Furthermore, the structures of E and Z isomers of 2-butenoic acid and oxiranecarboxylic acid derivatives as synthetic intermediates of compound (2) were studied. Among the derivatives, 3-[4-(2, 5-dihydro-1H-pyrrol-1-yl) phenyl]-2-oxobutanamide (6), 2-oxo-3-[4-(1-piperidinyl) phenyl] butanamide (8), 3-[4-(3-carboxypropanoylamino)-phenyl]-2-oxobutanamide (11), 3-[4-(2, 5-dihydro-2, 5-dioxo-1H-pyrrol-1-yl)-phenyl]-2-oxobutanamide (14), and N-benzyl-3-[4-(1, 3-dihydro-1-oxo-2H-isoindol-2-yl) phenyl]-2-oxobutanamide (16) showed potent anti-inflammatory activity comparable to phenylbutazone at the first screening with carragenin-induced rat paw edema.