In this study, the synthetic way to new N-pyridinyl(methyl)indolylpropanamides acting as non acidic NSAIDs has been described. Pharmacomodulation was carried out at N(1) and C(5) of the indole ring and at the level of the propanamide chain. N(3)-pyridinylmethyl-[1(4-chlorobenzyl-5-chloroindol-3-yl)propanamide represents one of the most potent compounds in the TPA-induced mouse ear swelling assay, with a level of activity higher than that of ibuprofen and comparable to that of dexamethasone.