Bezafibrate
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| Systematic (IUPAC) name |
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2-(4-{2-[(4-chlorobenzoyl)amino]ethyl}phenoxy)-2-methylpropanoic acid
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| Clinical data |
| AHFS/Drugs.com |
International Drug Names |
| MedlinePlus |
a682711 |
| Legal status |
- UK: Prescription-only (POM)
- US: ℞-only
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Routes of
administration |
Oral |
| Identifiers |
| CAS Registry Number |
41859-67-0 Y |
| ATC code |
C10AB02 |
| 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
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O=C(c1ccc(Cl)cc1)NCCc2ccc(OC(C(=O)O)(C)C)cc2
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InChI
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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
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Key:IIBYAHWJQTYFKB-UHFFFAOYSA-N Y
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| Y (what is this?) (verify) |
Bezafibrate (marketed as Bezalip and various other brand names) is a fibrate drug used for the treatment of hyperlipidaemia. It helps to lower LDL cholesterol and triglyceride in the blood, and increase HDL.
Contents
- 1 History
- 2 Mode of action
- 3 Uses
- 4 Side-effects
- 5 Other uses
- 6 Synthesis
- 7 References
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.[1] The main effect on cardiovascular morbidity is in patients with the metabolic syndrome, the features of which are attenuated by bezafibrate.[2] Studies show that in patients with impaired glucose tolerance, bezafibrate may delay progress to diabetes,[3] and in those with insulin resistance it slowed progress in the HOMA severity marker.[4] 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.[5]
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.[6]
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.[7]
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.
References
- ^ "Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease: the Bezafibrate Infarction Prevention (BIP) study". Circulation 102 (1): 21–7. 2000. doi:10.1161/01.cir.102.1.21. PMID 10880410.
- ^ Tenenbaum, A; Motro, M; Fisman, EZ; Tanne, D; Boyko, V; Behar, S (2005). "Bezafibrate for the secondary prevention of myocardial infarction in patients with metabolic syndrome". Archives of Internal Medicine 165 (10): 1154–60. doi:10.1001/archinte.165.10.1154. PMID 15911729.
- ^ Tenenbaum, A; Motro, M; Fisman, EZ; Schwammenthal, E; Adler, Y; Goldenberg, I; Leor, J; Boyko, V; et al. (2004). "Peroxisome proliferator-activated receptor ligand bezafibrate for prevention of type 2 diabetes mellitus in patients with coronary artery disease". Circulation 109 (18): 2197–202. doi:10.1161/01.CIR.0000126824.12785.B6. PMID 15123532.
- ^ Tenenbaum, A; Fisman, EZ; Boyko, V; Benderly, M; Tanne, D; Haim, M; Matas, Z; Motro, M; Behar, S (2006). "Attenuation of progression of insulin resistance in patients with coronary artery disease by bezafibrate". Archives of Internal Medicine 166 (7): 737–41. doi:10.1001/archinte.166.7.737. PMID 16606809.
- ^ Teramoto T, Shirai K, Daida H, Yamada N. Effects of bezafibrate on lipid and glucose metabolism in dyslipidemic patients with diabetes: the J-BENEFIT study. Cardiovascular Diabetology 2012, 11:29. http://www.cardiab.com/content/11/1/29, PMID 22439599
- ^ Dumont M, Stack C, Elipenahli C, Jainuddin S, Gerges M, Starkova N, Calingasan NY, Yang L, Tampellini D, Starkov AA, Chan RB, Di Paolo G, Pujol A, Beal MF (2012). "Bezafibrate administration improves behavioral deficits and tau pathology in P301S mice". Human Molecular Genetics 21 (23): 5091–5105. doi:10.1093/hmg/dds355. PMID 22922230.
- ^ "Contraceptive,Cholestrol - lowering drugs used to treat cancer. - Science daily".
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Lipid modifying agents (C10)
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|
| GI tract |
| Cholesterol absorption inhibitors, NPC1L1 |
|
|
| Bile acid sequestrants/resins (LDL) |
- Cholestyramine
- Colestipol
- Colestilan
- Colextran
- Colesevelam
|
|
|
| Liver |
| Statins (HMG-CoA reductase, LDL) |
- Simvastatin#
- Atorvastatin
- Fluvastatin
- Lovastatin
- Mevastatin
- Pitavastatin
- Pravastatin
- Rosuvastatin
- Cerivastatin‡
|
|
| Niacin and derivatives (HDL and LDL) |
- Niceritrol
- Niacin
- Nicofuranose
- Aluminium nicotinate
- Nicotinyl alcohol
- Acipimox
|
|
| MTTP inhibitors (VLDL) |
- Dirlotapide
- Lomitapide
- Mitratapide
|
|
|
| Blood vessels |
| Fibrates (PPAR) |
- Clofibrate‡
- Bezafibrate
- Aluminium clofibrate
- Gemfibrozil
- Fenofibrate
- Simfibrate
- Ronifibrate
- Ciprofibrate
- Etofibrate
- Clofibride
- Clinofibrate
|
|
| CETP inhibitors (HDL) |
- Anacetrapib†
- Dalcetrapib§
- Evacetrapib†
- Torcetrapib§
|
|
|
| Combinations |
- Niacin/lovastatin
- Niacin/simvastatin
- Ezetimibe/simvastatin
- Ezetimibe/atorvastatin
- Niacin/laropiprant
|
|
| Other |
- Dextrothyroxine‡
- Probucol
- Tiadenol
- Benfluorex
- Meglutol
- Omega-3-triglycerides
- Magnesium pyridoxal 5-phosphate glutamate
- Policosanol
- Lapaquistat§
- Mipomersen
- Alipogene tiparvovec
|
|
- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
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Index of nutrition
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|
| Description |
- Vitamins
- Cofactors
- Metal metabolism
- Fats
- metabolism
- intermediates
- lipoproteins
- Sugars
- Glycolysis
- Glycogenesis and glycogenolysis
- Fructose and galactose
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|
| Disease |
- Vitamins
- Carbohydrate
- Lipid
- Metals
- Other
- Symptoms and signs
- Tests
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| Treatment |
- Drugs
- Vitamins
- Mineral supplements
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