Bezafibrate

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.

Bezafibrate

Clinical data
AHFS/Drugs.com	International Drug Names
MedlinePlus	a682711
Routes of administration	Oral
ATC code	C10AB02 (WHO)
Legal status
Legal status	UK: POM (Prescription only) US: ℞-only
Identifiers
IUPAC name 2-(4-{2-[(4-chlorobenzoyl)amino]ethyl}phenoxy)-2-methylpropanoic acid
CAS Number	41859-67-0 Y
PubChem CID	39042
IUPHAR/BPS	2668
DrugBank	DB01393 Y
ChemSpider	35728 Y
UNII	Y9449Q51XH
KEGG	D01366 Y
ChEBI	CHEBI:47612 Y
ChEMBL	ChEMBL264374 Y
CompTox Dashboard (EPA)	DTXSID3029869
ECHA InfoCard	100.050.498
Chemical and physical data
Formula	C19H20ClNO4
Molar mass	361.82 g·mol−1
3D model (JSmol)	Interactive image
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
(verify)

It was patented in 1971 and approved for medical use in 1978.^[1]

Medical uses

Bezafibrate improves markers of combined hyperlipidemia, effectively reducing LDL and triglycerides and improving HDL levels.^[2] The main effect on cardiovascular morbidity is in patients with the metabolic syndrome, the features of which are attenuated by bezafibrate.^[3] Studies show that in patients with impaired glucose tolerance, bezafibrate may delay progress to diabetes,^[4] and in those with insulin resistance it slowed progress in the HOMA severity marker.^[5] 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.^[6]

Side-effects

The main toxicity is hepatic (abnormal liver enzymes); myopathy and on rare occasions 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.^[7]

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.^[8]

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.^[9]

Synthesis

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

Bezafibrate synthesis:^[10][11]

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.

History

Bezafibrate was first introduced by Boehringer Mannheim in 1977.