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

Journal of Medicinal Chemistry
J M JanuszR W Farmer

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.

Citations

Nov 16, 2002·Prostaglandins & Other Lipid Mediators·Lawrence J Marnett
Jan 11, 2001·Pharmacology & Therapeutics·R D MacPherson
Jul 12, 2000·European Journal of Medicinal Chemistry·G DannhardtB Fiebich
Mar 28, 2003·European Journal of Medicinal Chemistry·Holger UlbrichGerd Dannhardt
Feb 23, 2002·Bioorganic & Medicinal Chemistry Letters·Sabine BarbeyJean Pierre Hénichart
May 9, 2003·Bioorganic & Medicinal Chemistry·Masanao InagakiTatsuo Tsuri
Oct 2, 2014·Journal of Veterinary Internal Medicine·S D DumuscI A Burgener
Jul 1, 2011·Expert Opinion on Therapeutic Patents·Baker Jawabrah Al-HouraniFrank Wuest
Dec 23, 2016·Medicinal Research Reviews·Catarina Pereira-LeiteSalette Reis
Nov 9, 2011·Chemistry : a European Journal·Nuria RodríguezLukas J Goossen
Oct 3, 2018·SAR and QSAR in Environmental Research·Y XiA Yan
Dec 12, 2001·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·A BertoliniM Sandrini
Feb 15, 2019·Journal of Chemical Information and Modeling·Zijian QinAixia Yan
Sep 17, 2019·The Journal of Organic Chemistry·Brian J GroendykeSilas P Cook
Dec 26, 2007·Bioorganic & Medicinal Chemistry·Aurelio OrjalesM Teresa Núñez

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