SYNTHESIS, ANTIINFLAMMATORY ACTIVITY AND MOLECULAR-ORBITAL STUDIES OFA SERIES OF BENZYLIDENEAMINOXYPROPIONIC ACIDS SUBSTITUTED ON THE PHENYL RING

An examination of the antiinflammatory properties of certain beta-amin oxypropionic acids A (AOPAs) previously synthe- sized as analogs of an tiinflammatory drugs with an arylacetic structure B (ArAAs), indicated that the most active acid is the (E)-3-(benzylideneaminoxy)-propionic acid (1), which was found to possess an activity comparable to that o f Diclofenac (8). In an attempt to verify whether appropriate substitu tions on the aromatic ring of 1 can modulate the antiinflammatory prop erties of this class of drugs, a series of benzylideneaminoxypropionic acids (BAOPAs) were synthesized, in which the phenyl group is substit uted, in its 3 possible positions, by groups possessing different elec tronic, steric, and lipophilic characteristics. The antiinflammatory a ctivity of the new compounds was determined by carrageenan-induced rat paw edema, using Diclofenac (8) as the reference drug. The pharmacolo gical results revealed that among the BAOPAs examined, the most active are the m-chloro (7b) and p-ethoxy (7p) substituted compounds, which exhibit an antiinflammatory activity comparable to that of 1. Quantum mechanical calculations were also carried out in order to gain insight into the possible correlations between the pharmacological activity o bserved and the electronic and conformational effects induced by the p resence of the various substituents.