Synthesis and anti-HIV studies of 2- and 3-adamantyl-substituted thiazolidin-4-ones

A series of novel thiazolidin-4-ones bearing a lipophilic adamantyl substituent at position 2 or 3 were synthesized. A majority of them showed a modest anti-HIV-1 activity, whereas 2-adamantan-1-yl-3-(4,6-dimethylpyrimidin-2-yl)-thiazolidin-4-one (8) was endowed with a remarkable antiviral potency (EC(50)=0.67 microM). The new series of compounds (22-29) with an adamantyl moiety at the 3-position of the thiazolidinone ring showed good to modest anti-HIV-1 activity (EC(50)=1.0-11 microM) but also pronounced cytostatic activity. For example 24, 26 and 29 showed an EC(50) of 1.0-2.0 microM, while the 50% effective concentrations for 23 and 28 were 7.8 and 11.0 microM, respectively. X-ray studies and quantum chemical calculations revealed that the anti-HIV activity of the compounds strongly depends on their dipole moments and conformation of the thiazolidinones.