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

• Published in: European journal of medicinal chemistry 2000-03, Vol.35 (3), p.359-364
• Main Authors: Gürsoy, Aysel, Demirayak, Şeref, Çapan, Gültaze, Erol, Kevser, Vural, Kamil
• Format: Article
• Language: English
• Subjects: Acetic Acid; analgesic activity; Analgesics; Analgesics, Non-Narcotic - chemical synthesis; Analgesics, Non-Narcotic - pharmacology; Animals; Biological and medical sciences; Edema - chemically induced; Edema - prevention & control; Female; Formaldehyde; Male; Medical sciences; Mice; Neuropharmacology; oxazole; Pain Measurement - drug effects; Pharmacology. Drug treatments; Pyrazoles - chemical synthesis; Pyrazoles - pharmacology; pyrazolin-5-one; Structure-Activity Relationship; synthesis
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/S0223-5234(00)00117-3

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. 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.