Synthesis and preliminary evaluation of new 5-pyrazolinone derivatives as analgesic agents

Eur J Med Chem. 2000 Mar;35(3):359-64. doi: 10.1016/s0223-5234(00)00117-3.

Abstract

New 4-(aroyloxyalkanoyl)-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one s (5) were cyclized to 4-(2-aryl-5-unsubstituted/substituted oxazol-4-yl)-2,3-dimethyl-1-phenyl-3-pyrazolin-5-ones (6) employing the Davidson procedure. Preliminary evaluation of analgesic activity revealed that the effect of 4-(2-phenyl-5-ethyloxazol-4-yl)-2, 3-dimethyl-1-phenyl-3-pyrazolin-5-one and 4-[2-(4-chlorophenyl)-5-ethyloxazol-4-yl]-2, 3-dimethyl-1-phenyl-3-pyrazoline-5-one on acetic acid induced writhing was superior to that of antypyrine and aminopyrine. 4-[2-(4-Chlorophenyl)-5-methyloxazol-4-yl]-2, 3-dimethyl-1-phenyl-3-pyrazolin-5-one and 4-[2-(4-methoxyphenyl)-5-ethyloxazol-4-yl]-2, 3-dimethyl-1-phenyl-3-pyrazolin-5-one were more potent than aminopyrine, whereas 4-(2-phenyl-5-methyloxazol-4-yl)-2, 3-dimethyl-1-phenyl-3-pyrazolin-5-one and 4-[2-(4-methoxyphenyl)-5-methyl-oxazol-4-yl]-2, 3-dimethyl-1-phenyl-3-pyrazolin-5-one were not as active (modified Koster's Test; 0.19-0.21 mmol.kg(-1)). None of the selected entries showed inhibition of formaldehyde-induced paw oedema.

MeSH terms

  • Acetic Acid
  • Analgesics, Non-Narcotic / chemical synthesis*
  • Analgesics, Non-Narcotic / pharmacology
  • Animals
  • Edema / chemically induced
  • Edema / prevention & control
  • Female
  • Formaldehyde
  • Male
  • Mice
  • Pain Measurement / drug effects
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / pharmacology
  • Structure-Activity Relationship

Substances

  • Analgesics, Non-Narcotic
  • Pyrazoles
  • Formaldehyde
  • Acetic Acid