SYNTHESIS AND ANTIINFLAMMATORY ACTIVITY OF 2,6-BIS(1,1-DIMETHYLETHYL)PHENOL DERIVATIVES

The influence of 11 newly synthesized 2,6-bis(1,1-dimethylethyl) pheno l derivatives substituted in the 4 position as measured on the carrage enan paw edema assay in Sprague-Dawley rats, was studied using indomet hacin as a reference drug. Furthermore we studied the possible interfe rence of few of these compounds on the calcium binding sites by using the specific ligand [H-3]-PN 200-110 in ''in vitro'' experiments. As f ar as regard the antiinflammatory activity only the compounds 2b, 2j a nd 2k, dosed at 20 mg/Kg/os, exerted an inhibitory effect on paw edema which was practically equal after 6 h, to that of indomethacin (appro ximately 30%) dosed at 2.5 mg/Kg. The compound 2k, however, showed, in comparison with indomethacin and the other new tested compounds, a lo nger lasting effect, reaching, after 8 h, a 56.7% inhibition of the ed ema. Finally the above mentioned compounds, when tested alone or in co mbination with nitrendipine, did not exert any displacing activity on [H-3]-PN 200-110 binding to synaptosomal membranes. It is noteworthy h owever that compound 2e, which incidentally was inactive as antiinflam matory agent, showed a negative allosteric modulatory activity on the ability of nitrendipine to displace [H-3]-PN 200-110 binding.