Synthesis and preliminary evaluation of new 5-pyrazolinone derivatives as analgesic agents.
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.
Gürsoy
A
A
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Istanbul, 34452 Beyazit, Istanbul, Turkey. ayselgursoy@yahoo.com
Demirayak
S
S
Capan
G
G
Erol
K
K
Vural
K
K
D019342:Acetic Acid; D018712:Analgesics, Non-Narcotic / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D005260:Female; D005557:Formaldehyde; D008297:Male; D051379:Mice; D010147:Pain Measurement / Q000187:drug effects; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D018712:Analgesics, Non-Narcotic; D011720:Pyrazoles; D005557:Formaldehyde; D019342:Acetic Acid