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.

6-Halogen derivatives of 2-(3-benzoylphenyl)propionic acid / Cignarella, G; Curzu, Mm; Grella, G; Loriga, M; Anania, Vittorio Domenico; Desole, Maria Speranza. - In: IL FARMACO. EDIZIONE SCIENTIFICA. - ISSN 0430-0920. - 28:3(1983), pp. 187-198.

6-Halogen derivatives of 2-(3-benzoylphenyl)propionic acid.

ANANIA, Vittorio Domenico;DESOLE, Maria Speranza
1983

Abstract

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.
6-Halogen derivatives of 2-(3-benzoylphenyl)propionic acid / Cignarella, G; Curzu, Mm; Grella, G; Loriga, M; Anania, Vittorio Domenico; Desole, Maria Speranza. - In: IL FARMACO. EDIZIONE SCIENTIFICA. - ISSN 0430-0920. - 28:3(1983), pp. 187-198.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11388/140600
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