1,4-Dihydronaphthoquinones, hydroindoloquinones, benzofurans, and benzothiophenes as inhibitors of 5-lipoxygenase. Synthesis and structure-activity studies

Article abstract of DOI:10.1021/jm00164a050

A series of substituted 1,4-dihydronaphthoquinones, hydroindoloquinones, benzofuran-4,7-dihydroquinones, and benzothiophene-4,7-dihydroquinones were synthesized and evaluated for inhibitory activity against 5-lipoxygenase. These compounds were found to be active in vitro for LTC₄/D₄ inhibition with the potencies (IC₅₀'s) ranging from 0.2 to 85 μM. Active 1,4-dihydronaphthoquinone acetates (IC₅₀ < 20 μM) were evaluated in an ex vivo LTB₄ inhibition assay. The acetates of 1,4-dihydronaphthoquinones containing the alkyl substituent(s) (2-n-butyl, 11, and 2,3-diethyl, 15) exhibited the best activity in LTC₄/D₄ inhibition (IC₅₀ = 0.2-0.4 μM, in vitro) as well as in LTB₄ inhibition (60-75% inhibition).