Synthesis and anti-inflammatory activity of fluorinated phenyl styryl ketones and N-phenyl-5-substituted aryl-3-p-(fluorophenyl) pyrazolins and pyrazoles.
Various N-phenyl-5-substituted aryl-3-p-(fluorophenyl) pyrazolins and pyrazoles were synthesized by cyclization of the corresponding 4-(fluorophenyl) styryl and 4-(fluorophenyl) dibromostyryl ketones. These compounds were characterized by elemental analysis and UV, infrared, and nuclear magnetic spectral data. All substituted p-(fluorophenyl) styryl ketones [250 mg/kg orally (po)] possessed anti-inflammatory activity, as reflected by their ability to provide protection (51-70%) against carrageenin-induced edema in rat paw. Indomethacin (10 mg/kg, po) and dehydrozingerone (70 mg/kg, po), used as standard reference drugs, provided 97 and 60% protection, respectively. All compounds (0.20 mM) showed ability to denature bovine serum albumin, as observed in in vitro inhibition studies. Inhibition ranged from 7 to 59% for substituted p-(fluorophenyl) styryl ketones and from 12 to 21% for pyrazoles. No correlation was found between the anti-inflammatory activity of p-(fluorophenyl) styryl ketones or substituted pyrazoles and their effectiveness at inhibiting bovine serum albumin denaturation. The low toxicity of p-(fluorophenyl) styryl ketones was reflected by the dose that was lethal in 50% of the cases tested (2000-2500 mg/kg).
Nargund
L V
LV
Department of Pharmaceutical Chemistry, College of Pharmacy, J. N. Medical College, Belgaum, India.
Hariprasad
V
V
Reedy
G R
GR
D000818:Animals; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology*; D005260:Female; D007659:Ketones / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D007928:Lethal Dose 50; D008297:Male; D011489:Protein Denaturation / Q000187:drug effects; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D013329:Structure-Activity Relationship
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007659:Ketones; D011720:Pyrazoles