Anti-AIDS agents 66: Syntheses and anti-HIV activity of phenolic and aza 3′,4′-di-O-(−)-camphanoyl-(+)-cis-khellactone (DCK) derivatives

New phenolic and aza 3′,4′-di-O-(−)-camphanoyl-(+)-cis-khellactone (DCK) analogs were synthesized and assayed for inhibition of HIV-1 IIIB replication in H9 lymphocytes. Compound 16, 4-methyl-1′-aza-DCK (4-methyl-aza-DCK), was less lipophilic than 4-methyl-DCK, and retained sub-micromolar anti-HIV activity with EC50 and TI values of 0.77 μM and >42, respectively. Moreover, it showed moderately improved metabolic stability. Introduction of phenolic hydroxyl groups to 4-methyl-DCK decreased lipophilicity significantly, but did not improve metabolic stability and also decreased activity.

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