Acta Pharm. 58 (2008) 467-477
Synthesis and biological evaluation of some 4-(1H-indol-3-yl)-6-phenyl 1,2,3,4-tetrahydropyrimidin-2-ones/thiones as potent anti-inflammatory agents
MOHAMMAD AMIR, SADIQUE AKHTAR JAVED and HARISH KUMAR
Department of Pharmaceutical Chemistry, Faculty of
Accepted October x, 2008
Twelve new 4-(1H-indol-3-yl)-6-phenyl-1,2,3,4-tetrahydropyrimidin-2-ones/thiones (7-18) have been synthesized by reacting 1-aryl-3-(1H-indol-3-yl)-2-propen-1-one with urea and thiourea in ethanolic potassium hydroxide. Their structures have been confirmed by IR, 1H NMR and mass spectral data. The compounds were tested for their anti-inflammatory activity. Test results revealed that compounds showed 49.5 to 70.7% anti-inflammatory activity whereas the standard drug ibuprofen showed 86.4% activity at the same oral dose. Four compounds, 4-(1H-indol-3-yl)-6-(4-chlorophenyl-1,2,3,4-tetrahydropyrimidin-2-one (8), 4-(1H-indol-3-yl)-6-(4-methylphenyl-1,2,3,4-tetrahydropyrimidin-2-one (10), 4-(1H-indol-3-yl)-6-(4-chlorophenyl-1,2,3,4-tetrahydropyrimidin-2-thione (14), 4-(1H-indol-3-yl)-6-(4-methylphenyl-1,2,3,4-tetrahydropyrimidin-2-thione (16), that showed significant anti-inflammatory activity were selected to study their ulcerogenic and lipid peroxidation activities. All tested compounds showed significant reduction in the ulcerogenic potential and lipid peroxidation compared to the standard drug ibuprofen.
Keywords: pyrimidine derivatives, anti-inflammatory activity, ulcerogenicity, lipid peroxidation