Clofibrate analogues

It has long been known that clofibrate increases hepatic peroxisomes but whether a relationship exists between peroxisome proliferation and the hypolipidemic action of the drug has not been established. Several hypolipidemic clofibrate analogues did not proliferate hepatic mlcrosomes in rats, thus suggesting that both effects occur independently. ... 

The classic example of a peroxisome proliferator is clofibrate. This compound was developed as a drug for the treatment of hyperlipidaemia disorders. Given to rodents, it induces the proliferation in the liver of peroxisomes and, at high concentrations over a prolonged period of time, induces the development of hepatomas. A number of other compounds are now known to possess this property, many of them structural analogues of clofibrate (Reddy and Rao, 1986). 

The clinical success of clofibrate has naturally led to the synthesis of numerous analogues intended for use as hypocholesterolemic agents. One of these, clofenpyride (84), is synthesized readily from p-< hlorophenoxy-2,2-dimethylacetic acid (83) by conversion to the acid chloride and reaction with 3-hydroxy-40... 

BezafIbrate - Bezafibrate ( ), an analogue of clofibrate, had similar effects on serum lipids and lipoproteins as did clofibrate, but at lower doses. The pharmacologic spectrum of both drugs in rats was similar. In man, bezafibrate lowered serum triglycerides HDL-C in-... 

Based on the same hypothesis. Hammock et al. (1978) bioassayed analogues of the hypocholesterolaemic agent ethyl a-(4-chlorophenoxy)-a-methylpropionate (clofibrate, 106), tested earlier by Matolcsy et al. (1974a, 1974b), and fouhd that the acute symptoms on the test insects were similar to those induced by precocene II (74). 

Graham, M. J., M. A. Winham, S. L. Old, and T. J. B. Gray. 1996. Comparative hypolipidemic and peroxisomal effects of ciprofibrate, clofibric acid, and their respective difluorocy-clopropyl and 4-fluoro-substituted analogues in rat. Xenobiotica 26 695-707. 

The drug happens to be a structural analogue of clofibric acid. Contrary to clofibrate it helps to raise HDL levels but at the same time triglyceride levels are reduced appreciably. Interestingly, the drug is invariably employed in diet-refractory hypertriglyceridemia. ... 

In 1999, Bettoni and colleagues developed a DKR in order to prepare 2-aryloxyacid analogues of clofibrate, which show markedly different biological activities depending on the nature of the enantiomer. The key step of the synthesis was the condensation of sodium 4-chlorophenoxide on diastereomeric 2-bromoimides." (45)-4-Isopropyl-l,3-oxazolidin-2-one was used as the chiral auxiliary, as shown in Scheme 1.8. 

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