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

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 microM. Active 1,4-dihydronaphthoquinone acetates (IC50 less than 20 microM) 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 microM, in vitro) as well as in LTB4 inhibition (60-75% inhibition).