Derivatives of (phenylsulfanyl)benzoic acids with multiple antileukotrienic activity

摘要

A series of derivatives of (phenylsulfanyl) benzoic acids bearing quinoline, 2,4-dihydroxy-3- propylacetophenone and 2,4-difluorobiphenyl moieties were prepared and their antileukotrienic activities evaluated. Some of the compounds were found to display multiple antileukotrienic effect in the inhibition of LTB4 biosynthesis, binding to LTD4 and LTB4 receptors, superior to the standards ( zileuton and zafirlukast) used. The compounds had an antiinflammatory effect, manifested with quinoline derivatives by a significant inhibition of bronchospasm induced by LTD4 and/or albumin. The results of regression analysis correspond to the observation that the most active compounds belong to quinoline derivatives with the lowest lipophilicity. X-ray analysis of the quinoline compounds revealed that an intramolecular hydrophobic interaction of their aromatic rings does not occur in the solid state.