Bezafibrate CAS 41859-67-0
Introduction：Basic information about Bezafibrate CAS 41859-67-0, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
Bezafibrate Basic information
| Product Name: | Bezafibrate |
| Synonyms: | Bezafibrate D6 (dimethyl D6);Bezabrate D6 (DiMethyl D6);2-(4-{2-[(4-chlorophenyl)forMaMido]ethyl}phenoxy)-2-Methylpropanoic acid;Bezafibrate-d6;BEZAFIBRATE EPB(CRM STANDARD);BEZAFIBRATE MM(CRM STANDARD);bezafibrat;bezafibrato |
| CAS: | 41859-67-0 |
| MF: | C19H20ClNO4 |
| MW: | 361.82 |
| EINECS: | 255-567-9 |
| Product Categories: | Intracellular receptor;Intermediates & Fine Chemicals;Pharmaceuticals;Active Pharmaceutical Ingredients;Pharmaceutical intermediates;Cardiovascular Drugs |
| Mol File: | 41859-67-0.mol |
Bezafibrate Chemical Properties
| Melting point | 184 °C |
| Boiling point | 572.1±45.0 °C(Predicted) |
| density | 1.260±0.06 g/cm3(Predicted) |
| storage temp. | 2-8°C |
| solubility | DMF: soluble |
| form | solid |
| pka | 3.29±0.10(Predicted) |
| color | White to Off-White |
| Merck | 14,1195 |
| Stability: | Hygroscopic |
| 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) |
| InChIKey | IIBYAHWJQTYFKB-UHFFFAOYSA-N |
| SMILES | C(O)(=O)C(OC1=CC=C(CCNC(=O)C2=CC=C(Cl)C=C2)C=C1)(C)C |
| LogP | 2.504 (est) |
| CAS DataBase Reference | 41859-67-0(CAS DataBase Reference) |
| EPA Substance Registry System | Propanoic acid, 2-[4-[2-[(4-chlorobenzoyl)amino]ethyl]phenoxy]-2-methyl- (41859-67-0) |
Safety Information
| Hazard Codes | Xn |
| Risk Statements | 22 |
| Safety Statements | 36 |
| WGK Germany | 1 |
| RTECS | UE8755000 |
| HS Code | 29242990 |
| Storage Class | 11 - Combustible Solids |
| Hazard Classifications | Acute Tox. 4 Oral |
| Toxicity | LD50 oral in rat: 1082mg/kg |
| Description | Bezafibrate is a non-selective agonist of peroxisome proliferator-activated receptors (PPARs; EC50s = 50, 60, and 20 μM for human PPARα, PPARγ, and PPARδ, respectively). It reduces triglyceride levels and the size of lipid droplets in an oleic acid-induced HepaRG hepatocyte model of steatosis when used at a concentration of 25 μM. Bezafibrate (10 mg/kg per day) reduces plasma VLDL and LDL mass and triglyceride and free fatty acid levels in a high-fructose plus lard diet-induced rat model of insulin resistance. |
| Chemical Properties | Off-White Solid |
| Originator | Bezafibrate,Eipico Co. |
| Uses | Antilipemic |
| Uses | antihyperlipidemic |
| Uses | anti-hyperlipoproteinemic |
| Uses | Bezafibrate has been used:
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| Definition | ChEBI: Bezafibrate is a monocarboxylic acid amide obtained by the formal condensation of the carboxy group of 4-chlorobenzoic acid with the amino group of 2-[4-(2-aminoethyl)phenoxy]-2-methylpropanoic acid. Benafibrate is used for the treatment of hyperlipidaemia. It has a role as a xenobiotic, an environmental contaminant, a geroprotector and an antilipemic drug. It is a monocarboxylic acid, an aromatic ether, a member of monochlorobenzenes and a monocarboxylic acid amide. It is functionally related to a propionic acid. |
| Manufacturing Process | 0.292 moles p-chlorobenzoyl chloride and 50 ml dry pyridine were addeddropwise to 0.146 moles tyramine in 60 ml dry pyridine for 10 minutes. Thenthe mixture was poured in about 500 g of ice with water. The fallen-outcrystals was filtered off, washed with diluted HCl, water and NaHCO3 solutionand dried. It was recrystallized from acetone to give di(4-chlorobenzoyl)tyramine; yield 98 %; MP: 203°-205°C. 0.11 moles above product in 400 ml methanol was mixed with 130 ml 2 NKOH and heated at 40°-45°C for 1 hour. On cooling 130 ml 2 N HCl wasadded. The fallen-out precipitate was filtered off, filtrate was distilled off todryness. The residue was washed with water, NaHCO3 solution andrecrystallized from ethanol to give N-(4-chlorobenzoyl)tyramine; yield 91%;MP: 174°-176°C. 2.14 g sodium was dissolved in 50 ml of absolute methanol and mixed with0.93 mole N-(4-chlorobenzoyl)tyramine. Methanol was removed in vacuum todryness. The residue was slurried in 100 ml absolute toluene and 0.137 moles2-bromo-2-methylpropionic acid ethyl ester was added. The suspension washeated for 25 hours at 80°C. Then it was distilled in vacuum to dryness andthe residue was dissolved in CH2Cl2, washed with diluted HCl, NaOH andwater, and dried over CaCl2. On removing of the solvent, the crude 2-{4-[2-(4-chlorobenzoylamino)ethyl]phenoxy}-2-methylpropionic acid ethyl ester wasobtained. After recrystallization from ether/ ligroin and acetone it had MP:96°-97°C; yield 67 %. 0.1 mole above ester in 1.5 L of dioxane was slowly mixed with 200 ml 1 NKOH at ambient temperature and stood for 2 hours, then it was heated at40°C for 1 hour. The substance was dissolved completely. On cooling themixture was neutralized with 200 ml 1 N HCl. The solvents were removed invacuum. The residue was washed with water and recrystallized from acetoneto give 2-{4-[2-(4-chlorobenzoylamino)ethyl]phenoxy}-2-methylpropionicacid; yield 84%; MP: 186°C. |
| Therapeutic Function | Antihyperlipidemic |
| Biochem/physiol Actions | The peroxisome proliferator-activated receptor (PPAR) is a member of the steroid nuclear receptor superfamily. Bezafibrate is a peroxisome proliferator-activated receptor agonist for PPARα, PPARδ, and PPARγ. Lipoprotein lipase (LPL) activator.PPARgamma agonists, including Bezafibrate, have beneficial effects in the suppression of the inflammatory response during RSV infection and therefore might have clinical efficacy in the course of severe RSV-infection. |
| Clinical Use | Hyperlipidaemia |
| Drug interactions | Potentially hazardous interactions with other drugs Antibacterials: increased risk of myopathy with daptomycin - try to avoid concomitant use. Anticoagulants: enhances effect of coumarins and phenindione; dose of anticoagulant should be reduced by up to 50% and adjusted by monitoring INR. Antidiabetics: may improve glucose tolerance and have an additive effect with insulin or sulphonylureas. Ciclosporin: may increase nephrotoxicity and reduce ciclosporin levels. Colchicine: possible increased risk of myopathy. Lipid-regulating drugs: increased risk of myopathy in combination with statins and ezetimibe - avoid with ezetimibe; do not exceed 10 mg of simvastatin and 20 mg of rosuvastatin. |
| Metabolism | 50% of the administered bezafibrate dose is recovered in the urine as unchanged drug and 20% in the form of glucuronides. Elimination is rapid, with excretion almost exclusively renal. 95% of the activity of the [14C]-labelled drug is recovered in the urine and 3% in the faeces within 48 hours. |
| References | [1] ALEXANDRA ROGUE . PPAR agonists reduce steatosis in oleic acid-overloaded HepaRG cells[J]. Toxicology and applied pharmacology, 2014, 276 1: Pages 73-81. DOI: 10.1016/j.taap.2014.02.001 [2] H MATSUI. Improved insulin sensitivity by bezafibrate in rats: relationship to fatty acid composition of skeletal-muscle triglycerides.[J]. Diabetes, 1997, 46 3: 348-353. DOI: 10.2337/diab.46.3.348 |
Bezafibrate Preparation Products And Raw materials
| Raw materials | 4-Chlorobenzoyl chloride-->Tyramine-->Ethyl 2-bromoisobutyrate-->Sodium |
