Abstract
A series of 5-keto-substituted 7-tert-buty1-2,3-dihydro-3,3- dimethylbenzofurans (DHDMBFs) were found to be nonsteroidal antiinflammatory and analgesic agents. These compounds are inhibitors of 5-lipoxygenase (5-LOX) and cyclooxygenase (COX) with selectivity for the COX-2 isoform. A series of analogues were prepared to investigate the scope of this lead. Five ketone side chains from active DHDMBFs were used to investigate the effects of changes in the DHDMBF "core": the size and identity of the heterocycle and the substituent requirements of the heterocycle and phenyl ring. Biological testing showed that a variety of structural changes can be accommodated, but no structure was clearly superior to the DHDMBF structure.
MeSH terms
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Analgesics / chemical synthesis*
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Analgesics / chemistry
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Analgesics / pharmacology
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Animals
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Anti-Inflammatory Agents / chemical synthesis*
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Anti-Inflammatory Agents / chemistry
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Anti-Inflammatory Agents / pharmacology
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Benzofurans / chemical synthesis*
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Benzofurans / chemistry
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Benzofurans / pharmacology
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Blood Platelets / drug effects
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Blood Platelets / enzymology
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Carrageenan / adverse effects
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Cyclooxygenase Inhibitors / chemical synthesis*
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Cyclooxygenase Inhibitors / chemistry
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Cyclooxygenase Inhibitors / pharmacology
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Edema / chemically induced
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Edema / drug therapy
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Humans
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Lipoxygenase Inhibitors*
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Rats
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Rats, Inbred Lew
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Rats, Sprague-Dawley
Substances
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Analgesics
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Anti-Inflammatory Agents
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Benzofurans
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Cyclooxygenase Inhibitors
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Lipoxygenase Inhibitors
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Carrageenan