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)phenol derivatives substituted in the 4 position as measured on the carrageenan paw edema assay in Sprague-Dawley rats, was studied using indomethacin as a reference drug. Furthermore we studied the possible interference of few of these compounds on the calcium binding sites by using the specific ligand [3H]-PN 200-110 in "in vitro" experiments. As far as regard the antiinflammatory activity only the compounds 2b, 2j and 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 (approximately 30%) dosed at 2.5 mg/Kg. The compound 2k, however, showed, in comparison with indomethacin and the other new tested compounds, a longer lasting effect, reaching, after 8 h, a 56.7% inhibition of the edema. Finally the above mentioned compounds, when tested alone or in combination with nitrendipine, did not exert any displacing activity on [3H]-PN 200-110 binding to synaptosomal membranes. It is noteworthy however that compound 2e, which incidentally was inactive as antiinflammatory agent, showed a negative allosteric modulatory activity on the ability of nitrendipine to displace [3H]-PN 200-110 binding.
Tait
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Dipartimento di Scienze Farmaceutiche, Università di Modena.
Parenti
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Zanoli
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P
Veneri
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Truzzi
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Brandoli
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C
Baraldi
M
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di Bella
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M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D002118:Calcium / Q000737:chemistry; D002351:Carrageenan; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005260:Female; D017275:Isradipine / Q000378:metabolism; D008297:Male; D009568:Nitrendipine / Q000494:pharmacology; D010636:Phenols / Q000138:chemical synthesis* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000737:chemistry / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010636:Phenols; C036461:J 2644; D002351:Carrageenan; D009568:Nitrendipine; D002118:Calcium; D017275:Isradipine