Thiazolyl‐N‐substituted amides: A group of effective anti‐inflammatory agents with potential for local anesthetic properties. Synthesis,biological evaluation,and a QSAR approach

A series of thiazolyl‐N‐substituted amides were synthesized and tested for anti‐inflammatory activity. Their R_M values were determined as an expression of their lipophilicity. Theoretical calculation of their lipophilicity, as clog P and log D_7.4 was also performed. The effect of the synthesized compounds on inflammation, using the carrageenan‐induced mouse paw edema model was studied. In general, the studied compounds were found to be potent anti‐inflammatory agents (23.2–72.1%). Anti‐inflammatory activity was influenced by some structural characteristics of the synthesized compounds. An attempt was made to correlate their biological activity with some physicochemical parameters using a quantitative structure–activity relationship approach (QSAR). A parabolic dependence of activity from clog D_7.4 and a linear dependence from surface tension were found. The anti‐inflammatory activity of the thiazolyl‐amides were found to a great extent to be under pharmacokinetic control. Drug Dev. Res. 48:53–60, 1999. © 1999 Wiley‐Liss, Inc.