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

Abstract

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 μM). 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 μM) but also pronounced cytostatic activity. For example 24, 26 and 29 showed an EC ₅₀ of 1.0–2.0 μM, while the 50% effective concentrations for 23 and 28 were 7.8 and 11.0 μM, 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.

Graphical abstract