CHIRAL RESOLUTION, CONFIGURATIONAL STUDY AND PHARMACOLOGICAL PROFILE OF 2-PHENOXYPROPIONIC ACIDS

The racemates and several enantiomers of 2-phenoxypropionic acids, bea ring alkyl, acetyl, benzyl, benzoyl, phenyl, difluorophenyl, Cl, NO2 g roups on the aromatic moiety, were investigated as potential analgesic -antiinflammatory drugs. The enantiomers, whose absolute configuration has been previously determined by us, were prepared by chiral resolut ion of the diastereoisomeric salts of the racemates with cynchonidine. The enantiomeric excess was determined by chiral chromatography. The chiroptical properties of the dextroisomers were investigated by CD. T he pharmacological properties of the racemates and the enantiomers wer e monitored by analgesic-antiinflammatory activity tests as well as by gastrotolerability and acute toxicity tests. Some compounds were show n to be superior to ASA and ketoprofen because they have higher or sim ilar analgesic properties, with less gastroulcerogenetic activity. Fur thermore low acute toxicity was found for the compounds with high valu es of ED50. Correlations between the configuration of the enantiomers and their activity are not evident. For the most active compounds, the activity of one of the enantiomers is superior to that of the racemat es. This is particularly true for (S)-3, (R)-15 and (S)-18.