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

New 4-(aroyloxyalkanoyl)-2,3-dimethyl-1-phenyl-3-pyrazolin-5-ones (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. Prelimin ary evaluation of analgesic activity revealed that the effect of 4-(2-pheny l-5-ethyloxazol-4-yl)-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one and 4-[2-(4-c hlorophenyl)-5-ethyloxazol-4-yl]-2,3-dimethyl-1-phenyl-3-pyrazoline-5-one o n acetic acid induced writhing was superior to that of antypyrine and amino pyrine. 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- dimethy l-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-pyrazol in-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 pa w oedema. (C) 2000 Editions scientifiques et medicales Elsevier SAS.