PMID: 2104936Jan 1, 1990Paper

2-substituted-1-naphthols as potent 5-lipoxygenase inhibitors with topical antiinflammatory activity

Journal of Medicinal Chemistry
D G BattR R Harris

Abstract

The synthesis, biological evaluation, and structure-activity relationships of a series of 1-naphthols bearing carbon substituents at the 2-position are described. These compounds are potent inhibitors of the 5-lipoxygenase from RBL-1 cells and also inhibit bovine seminal vesicle cyclooxygenase. Structure-activity relationships for these two enzymes are different, implying specific enzyme inhibition rather than a nonspecific antioxidant effect. 2-(Aryl-methyl)-1-naphthols are among the most potent 5-lipoxygenase inhibitors reported (IC50 values generally 0.01-0.2 microM) and show excellent antiinflammatory potency in the mouse arachidonic acid ear edema model. To study the effects of structure on in vitro and in vivo activity, four general features of the molecules were varied: the 2-substituent, the 1-hydroxyl group, substitution on the naphthalene rings, and the 1,2-disubstituted naphthalene unit itself. 2-Benzyl-1-naphthol (5a, DuP 654) shows a very attractive profile of topical antiinflammatory activity and is currently in clinical trials as a topically applied antipsoriatic agent.

Citations

Nov 1, 1991·Archiv der Pharmazie·H TanzerW Wiegrebe
Apr 5, 1996·The Journal of Biological Chemistry·R D AbeysingheJ B Porter
Jul 19, 2014·Cancers·Rosalina Wisastra, Frank J Dekker
Oct 27, 2018·European Journal of Medicinal Chemistry·Subhajit MakarSushil K Singh
Aug 1, 1992·Trends in Pharmacological Sciences·R M McMillan, E R Walker
Jun 25, 2013·ACS Medicinal Chemistry Letters·Baisong ZhengYongcheng Song
May 6, 2015·The Journal of Organic Chemistry·Yoshinari SawamaHironao Sajiki
Oct 27, 2012·Organic Letters·Dongjin KangPhil Ho Lee
Jan 4, 2006·The Journal of Organic Chemistry·Xiaoxia ZhangRichard C Larock

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