Synthesis, anti-inflammatory and analgesic evaluation of thioxoquinazolinone derivatives

Abstract

A series of 3-substituted-2-thioxoquinazolin-4(3H)-one derivatives have been synthesized and their structures have been elucidated on the basis of IR, 1H-NMR, elemental analysis and mass spectroscopic studies. Anti-inflammatory and analgesic activity of the synthesized compounds was evaluated by Carrageenan induced rat paw edema method and Eddy's hot plate method respectively. Among the synthesized compounds N- (4-hydroxyphenyl) -N- (4-oxo-3-phenyl-2-thioxo-3,4-dihydroquinazolin-1 (2H) methyl) acetamide (PTQ01) showed excellent anti-inflammatory activity. N-(4-ethoxyphenyl) -N- (3-(naphthalen-2yl) -4-oxo-2-thioxo-3,4-dihydroquinazolin-1 (2H) -yl) methyl) acetamide (NTQ02), N- (4-Hydroxyphenyl) -N- ((3-naphthalen-2-yl) -4-oxo-2-thioxo-3,4-dihydorquinazolin-1 (2H) -ylmethyl) acetamide (NTQ01), N- ((3-(4-ethoxyphenyl) -4-oxo-2-thioxo-3,4-dihydoquinazolin-1 (2H) -yl) methyl) -N- (4-hydroxyphenyl)acetamide (ETQ01) N- (3-(4-ethoxyphenyl) -4-oxo-2thioxo-3,4-dihydroquinazolin-1 (2H) -ylmethyl) -N- (4-hydroxyphenyl) acetamide (ETQ04), N- (4-ethoxyphenyl) -N- ((4-oxo-3-phenyl-2-thioxo-3,4-dihydoquinazolin-1 (2H) -yl) methyl) acetamide (PTQ02) and N-(4-ethoxyphenyl)-N-(3-(4-ethoxyphenyl)-4-oxo-2-thioxo-3,4-dihydoquinazolin-1 (2H)-yl) methyl) acetamide (ETQ02) at a dose of 20 mg/kg exhibited significant anti-inflammatory activity compared to that of standard drug diclofenac sodium. The compound 2-(2,3-dimethylphenyl)(3-(4-ethoxyphenyl)-4-oxo-2-thioxo-3,4-di-hydroquinazolin-1-2H) -1ylmethylamino) benzoic acid PTQ03 and sodium 2- (2- ((2,6-dichlrophenyl)(3-(4-oxo-2-thiox-o-3,4-dihydroquinazolin-1 (2H)-yl) methyl) amino) phenylacetate (PTQ04) showed moderate anti-inflammatory activity. The compounds PTQ01, PTQ02, PTQ04, ETQ01 and ETQ02 showed significant analgesic activity compared with that of standard drug pentazocin. © 2011 The Pharmaceutical Society of Japan.