NEW CYCLOOXYGENASE-2 5-LIPOXYGENASE INHIBITORS - 1 - 7-TERT-BUTYL-2,3-DIHYDRO-3,3-DIMETHYLBENZOFURAN DERIVATIVES AS GASTROINTESTINAL SAFE ANTIINFLAMMATORY AND ANALGESIC AGENTS - DISCOVERY AND VARIATION OF THE 5-KETO SUBSTITUENT/

A series of 5-keto-substituted 7-tert-butyl-2,3-dihydro-3,3-dimethylbe nzofurans (DHDMBFs) were prepared and evaluated as potential nonsteroi dal antiinflammatory and analgesic agents. Interest in this class of c ompounds arose when a DHDMBF was found to be an active metabolite of t he di-tert-butylphenol antiinflammatory agent tebufelone. We have now found that a variety of 5-keto-substituted DHDMBFs have good in vivo a ntiinflammatory and analgesic activity after oral administration. Thes e compounds inhibit both cyclooxygenase (COX) and 5-lipoxygenase (5-LO X) in vitro. The cyclooxygenase inhibition was found to be selective f or the cyclooxygenase-2 isoform, and this combination of COX-2/5-LOX i nhibition may be responsible for the gastrointestinal safety of compou nds such as 30.