Bezafibrate

Bezafibrate

Systematic (IUPAC) name
2-(4-{2-[(4-chlorobenzoyl)amino]ethyl}phenoxy)-2-methylpropanoic acid
Clinical data
AHFS/Drugs.com	International Drug Names
MedlinePlus	a682711
Legal status	UK: POM (Prescription only) US: ℞-only
Routes of administration	Oral
Identifiers
CAS Number	41859-67-0 Y
ATC code	C10AB02 (WHO)
PubChem	CID: 39042
IUPHAR/BPS	2668
DrugBank	DB01393 Y
ChemSpider	35728 Y
UNII	Y9449Q51XH Y
KEGG	D01366 Y
ChEBI	CHEBI:47612 Y
ChEMBL	CHEMBL264374 Y
Chemical data
Formula	C19H20ClNO4
Molecular mass	361.819 g/mol
SMILES O=C(c1ccc(Cl)cc1)NCCc2ccc(OC(C(=O)O)(C)C)cc2
InChI InChI=1S/C19H20ClNO4/c1-19(2,18(23)24)25-16-9-3-13(4-10-16)11-12-21-17(22)14-5-7-15(20)8-6-14/h3-10H,11-12H2,1-2H3,(H,21,22)(H,23,24) Y Key:IIBYAHWJQTYFKB-UHFFFAOYSA-N Y
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Bezafibrate (marketed as Bezalip and various other brand names) is a fibrate drug used as a lipid-lowering agent to treat hyperlipidaemia. It helps to lower LDL cholesterol and triglyceride in the blood, and increase HDL.

History

Bezafibrate was first introduced by Boehringer Mannheim in 1977.

Mode of action

Like the other fibrates, bezafibrate is an agonist of PPARα; some studies suggest it may have some activity on PPARγ and PPARδ as well.

Uses

Bezafibrate improves markers of combined hyperlipidemia, effectively reducing LDL and triglycerides and improving HDL levels. The main effect on cardiovascular morbidity is in patients with the metabolic syndrome, the features of which are attenuated by bezafibrate. Studies show that in patients with impaired glucose tolerance, bezafibrate may delay progress to diabetes, and in those with insulin resistance it slowed progress in the HOMA severity marker. In addition, a prospective observational study of dyslipidemic patients with diabetes or hyperglycemia showed that bezafibrate significantly reduces haemoglobin A1c (HbA1c) concentration as a function of baseline HbA1c levels, regardless of concurrent use of antidiabetic drugs.

Side-effects

The main toxicity is hepatic (abnormal liver enzymes), and myopathy and rarely rhabdomyolysis have been reported.

Other uses

The Australian biotech company Giaconda combines bezafibrate with chenodeoxycholic acid in an anti-hepatitis C drug combination called Hepaconda.

Bezafibrate has been shown to reduce tau protein hyperphosphorylation and other signs of tauopathy in transgenic mice having human tau mutation.

The combination of a cholesterol-lowering drug, bezafibrate, and a contraceptive steroid, medroxyprogesterone acetate, could be an effective, non-toxic treatment for a range of cancers, researchers at the University of Birmingham have found.

Synthesis

Further evidence that substantial bulk tolerance is available in the para position is given by the lipid lowering agent bezafibrate.

Bezafibrate synthesis: E. Witte et al., DE 2149070 ; eidem, U.S. Patent 3,781,328 (both 1973 to Boehringer, Mann.).

The p-chlorobenzamide of tyramine undergoes a Williamson ether synthesis with ethyl 2-bromo-2-methylpropionate to complete the synthesis. The ester group is hydrolyzed in the alkaline reaction medium.