Design, synthesis and HIV-RT inhibitory activity of novel thiazolidin-4-one derivatives

A series of 2-aryl-3-(4,5,6-trimethylpyrimidin-2-yl) thiazolidin-4-ones (1a–1c) and their derivatives bearing a lipophilic substituent, like acetoxy group (3a–3c), propionyloxy group (4a–4c), methyl (5d and 5e) at C-5 on thiazolidin-4-one ring were designed, synthesized and evaluated for their HIV-RT inhibitory activity. Using selfcatalyzed Pummerer reaction, compounds 3a–3c and 4a–4c were obtained in good yield (63.1%–75.2%). Preliminary anti-HIV-RT test of these derivatives indicated that compounds 1a–1c, 4b (propionyloxy group at C-5) showed moderate HIV-RT inhibitory activity and compounds 5d and 5e with methyl at C-5 showed a weak HIVRT inhibitory activity. Structure activity relationship analysis suggested that the substituted groups on C-5 would be unfavorable to anti-HIV-RT activity and that the steric effect might play a critical role in the anti-HIV RT activity.