Metabolic chiral inversion of anti-inflammatory 2-arylpropionates: lack of reaction in liver homogenates, and study of methine proton acidity.
Xenobiotica
; 18(5): 533-43, 1988 May.
Article
em En
| MEDLINE
| ID: mdl-2840782
ABSTRACT
1. Enrichment in the (S)-enantiomers for (R)-flurbiprofen, (R)-naproxen, (R)-suprofen and (R;S)-ibuprofen was investigated in various subcellular hepatic preparations containing coenzyme A. While such preparations were able to form hippuric acid from benzoic acid, the chiral inversion was never seen. 2. Using 2-dimethylaminoethanethiol 2-phenylpropionate (DEPP) as a model acyl thioester, the acidity of the methine proton was investigated by monitoring the proton/deuterium exchange occurring in deuterated solvents using high-resolution n.m.r. The compound was inert up to 22 h in D2O at 37 degrees C and pD 7.4. In pure methanol or a methanol-water mixture, only solvolysis was seen. In contrast, competitive hydrolysis (k = 0.005 h-1) and proton/deuterium exchange (k = 0.09 h-1) were seen in a CD3CN/D2O (5050) mixture at 37 degrees C. 3. It is speculated that the failure to characterize chiral inversion of 2-arylpropionates in subcellular preparations may be due to the absence of a microenvironment of adequately moderate polarity.
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Base de dados:
MEDLINE
Assunto principal:
Anti-Inflamatórios não Esteroides
/
Fígado
Idioma:
En
Ano de publicação:
1988
Tipo de documento:
Article
País de afiliação:
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