M. Duflos, J. Courant, G. Baut
Jul 1, 1998
Citations
0
Influential Citations
7
Citations
Quality indicators
Journal
European Journal of Medicinal Chemistry
Abstract
Abstract The development of new potential anti-inflammatory compounds resulting from the incorporation of α-aminoacid residues into 6-amino-2,4-lutidine afforded (N-protected) aminoamides with interesting inhibitory activity. Out of 28 tested compounds, 10 ( 5a, 5b, 7d, 8a, 8b, 8d, 10a, 11b, 12a and 12b ) exerted potent (>90%) inhibition in the carrageenan foot edema (CFE) rat model after oral administration of 0.4 mmol kg −1 . Except for Cbz-glycyl, Cbz-alanyl, Fmoc-valyl and Cbz-alanyl-glycyl derivatives ( 5a, 5b, 7d and 11b ). N-deprotection afforded more active compounds. Introduction of a glycyl residue in the previously studied highly active 3-fluorobenzamide 2 , which led to 10a , maintained potent peripheral edema inhibition but had a detrimental effect in the acute TPA-induced mouse ear-swelling model. Glycylglycinamide 12a , which had an ID 50 of 9.0 mg kg −1 in the CFE test, appeared to be the most efficient compound tested in this new series of non-carboxylic nonsteroidal anti-inflammatory drugs. Glycinamide 8a , although less potent in the same assay (14.3 mg kg −1 ), exerted a significant inhibitory effect in acute and chronic ear-swelling tests after topical application of 3 mg/ear.