Urea/thiourea derivatives of Gly/Pro conjugated 2,3-dichlorophenyl piperazine as potent anti-inflammatory agents: SAR studies

Abstract

Two series of urea/thiourea derivatives of Gly/Pro conjugated 2,3-dichlorophenyl piperazine have been synthesized and characterized as novel anti-inflammatory agents. The results demonstrate that the derivatives <strong>1f</strong>, <strong>1g</strong>, <strong>1j</strong>, <strong>1k</strong>, <strong>2g</strong>, <strong>2j</strong> and <strong>2k</strong> show good anti-inflammatory properties with IC₅₀ values of 42 ± 0.32 µM, 30 ± 0.51 µM, 65 ± 0.61 µM, 60 ± 0.52 µM, 60 ± 0.22 µM, 57 ± 0.37 µM and 35 ± 0.15 µM respectively. These results reveal that compounds with electron withdrawing moieties (F and Cl) particularly at <em>para</em> position exhibit excellent anti-inflammatory activity compared to the standards indomethacin (IC₅₀= 58 ± 0.37 µM) and ibuprofin (IC₅₀ = 67 ± 0.43 µM).