6-Halogen derivatives of 2-(3-benzoylphenyl)propionic acid.
The synthesis of the 6-fluoro (I a), 6-chloro (I b) and 6-bromo (I c) derivatives of the known antiinflammatory agent 2-(3-benzoylphenyl)propionic acid (ketoprofen) is reported. The procedure employed involves the direct phase-transfer methylation of the appropriate arylacetonitriles and the subsequent hydrolysis of the alpha-methyl arylacetonitriles (V) thus obtained. It is noteworthy that (V b) and (V c) were not accompanied by alpha, alpha-dimethylated contaminants, owing to the steric hindrance of the chloro and bromine substituent. The pharmacological evaluation of (I a-c) showed that the presence of the halogen unexpectedly abolished the antiinflammatory and antipyretic activities of the model drug. The 6-ethoxy derivative (I d), isolated as by-product of the synthesis of (I a) was also found inactive. A hypothesis has been formulated on the loss of activity of these compounds.
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis*; D007660:Ketoprofen / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D010666:Phenylpropionates / Q000138:chemical synthesis*; D051381:Rats; D011919:Rats, Inbred Strains; D013696:Temperature
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010666:Phenylpropionates; D007660:Ketoprofen