Anti-AIDS agents. Part 62: Anti-HIV activity of 2′-substituted 4-methyl-3′,4′-di-O-(-)-camphanoyl-(+)-cis-khellactone (4-methyl DCK) analogs

Article abstract of DOI:10.1016/j.bmcl.2004.09.032

Four 4-methyl-3′,4′-di-O-(-)-camphanoyl-(+)-cis-khellactone (4-methyl DCK) analogs (7a-d) with different alkyl substituents at the 2′-position were synthesized and evaluated for inhibition of HIV-1 replication in H9 lymphocytes. 2′-Methyl-2′-ethyl-4-methyl DCK (7b) was more potent (EC₅₀ = 0.22 μM, TI > 175) than the other three compounds (7a, 7c, and 7d), but significantly less potent than 4-methyl DCK (2, EC₅₀ = 0.0059 μM, TI > 6600). Four 4-methyl-3′,4′- di-O-(-)-camphanoyl-(+)-cis-khellactone (4-methyl DCK) analogs (7a-d) with different alkyl substituents at the 2′-position were synthesized and evaluated for inhibition of HIV-1 replication in H9 lymphocytes. 2′-Methyl-2′-ethyl-4-methyl DCK (7b) was more potent (EC ₅₀ = 0.22 μM, TI > 175) than the other three compounds (7a, 7c, and 7d), but significantly less potent than 4-methyl DCK (2, EC₅₀ = 0.0059 μM, TI > 6600). The bioassay results indicated that the 2′-substituents had a strong effect on the anti-HIV activity, and gem-dimethyl substitution at the 2′-position was greatly preferable to larger alkyl substituents or hydrogen atoms.