New cyclooxygenase-2/5-lipoxygenase inhibitors. 1. 7-tert-buty1-2,3-dihydro-3,3-dimethylbenzofuran derivatives as gastrointestinal safe antiinflammatory and analgesic agents: discovery and variation of the 5-keto substituent.

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Citation

Janusz JM, Young PA, Ridgeway JM, Scherz MW, Enzweiler K, Wu LI, Gan L, Darolia R, Matthews RS, Hennes D, Kellstein DE, Green SA, Tulich JL, Rosario-Jansen T, Magrisso IJ, Wehmeyer KR, Kuhlenbeck DL, Eichhold TH, Dobson RL, Sirko SP, Farmer RW

New cyclooxygenase-2/5-lipoxygenase inhibitors. 1. 7-tert-buty1-2,3-dihydro-3,3-dimethylbenzofuran derivatives as gastrointestinal safe antiinflammatory and analgesic agents: discovery and variation of the 5-keto substituent.

J Med Chem. 1998 Mar 26;41(7):1112-23.

PubMed ID
9544211 [ View in PubMed
]
Abstract

A series of 5-keto-substituted 7-tert-buty1-2,3-dihydro-3,3- dimethylbenzofurans (DHDMBFs) were prepared and evaluated as potential nonsteroidal antiinflammatory and analgesic agents. Interest in this class of compounds arose when a DHDMBF was found to be an active metabolite of the di-tert-butylphenol antiinflammatory agent tebufelone. We have now found that a variety of 5-keto-substituted DHDMBFs have good in vivo antiinflammatory and analgesic activity after oral administration. These compounds inhibit both cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) in vitro. The cyclooxygenase inhibition was found to be selective for the cyclooxygenase-2 isoform, and this combination of COX-2/5-LOX inhibition may be responsible for the gastrointestinal safety of compounds such as 30.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
IbuprofenProstaglandin G/H synthase 2IC 50 (nM)30000N/AN/ADetails