Clofibrate

Base Information

• Chemical Name: Clofibrate
• CAS No.: 637-07-0
• Molecular Formula: C12H15ClO3
• Molecular Weight: 242.702
• Hs Code.: 29189900
• European Community (EC) Number: 211-277-4
• NSC Number: 758474,79389
• UNII: HPN91K7FU3
• DSSTox Substance ID: DTXSID3020336
• Nikkaji Number: J3.314F
• Wikipedia: Clofibrate
• Wikidata: Q2701912
• NCI Thesaurus Code: C378
• Pharos Ligand ID: K3RA4G6JV2HR
• Metabolomics Workbench ID: 42958
• ChEMBL ID: CHEMBL565
• Mol file: 637-07-0.mol

Synonyms:Athromidin;Atromid;Atromid S;Chlorophenoxyisobutyrate, Ethyl;Clofibrate;Clofibric Acid, Ethyl Ester;Ethyl Chlorophenoxyisobutyrate;Miscleron;Miskleron

Chemical Property of Clofibrate

Chemical Property:

• Appearance/Colour: Clear colorless oil
• Vapor Pressure: 0.00528mmHg at 25°C
• Melting Point: <25 °C
• Refractive Index: n20/D 1.503
• Boiling Point: 274.82 °C at 760 mmHg
• Flash Point: 115.064 °C
• PSA: 35.53000
• Density: 1.148 g/cm³
• LogP: 3.06050
• Storage Temp.: 2-8°C
• Solubility.: Soluble to 100 mM in DMSO.
• Water Solubility.: 97.08mg/L(room temperature)
• XLogP3: 3.3
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 5
• Exact Mass: 242.0709720
• Heavy Atom Count: 16
• Complexity: 232

Purity/Quality:

99%min ^*data from raw suppliers

Clofibrate ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn,N
• Hazard Codes: Xn,N
• Statements: 22-37/38-41-51/53-40
• Safety Statements: 26-36/37/39-61-45-36/37

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antilipemic Agents
• Canonical SMILES: CCOC(=O)C(C)(C)OC1=CC=C(C=C1)Cl
• Recent ClinicalTrials: Coronary Drug Project Mortality Surveillance
• Description: Researchers in France observed in 1953 that structures derived from dehydrocholic acid, phenylethyl acetic acid, and certain other disubstituted acetic acids exhibited hypocholesterolemic properties in rats and humans. Several years later, Thorp and Waring discovered clof ibrate as an effective compound for lowering lipids in animal models, with minimal toxicity. Its mode of action was initially attributed to seasonal variations in adrenal and thyroid function, and the administration of androsterone was found to potentiate the hypocholesterolemic effect of this compound. Subsequently, several clinical trials were performed which showed that clofibrate decreases lipid levels in hypercholesterolemic patients, mainly as the result of a reduction in the very-low-density lipoprotein (VLDL), and less in the low-density lipoprotein (LDL) fraction, and that the coadministration of androsterone was not necessary for its hypolipidemic effect. Despite reported hepatomegaly in rats following long-term treatment with clofibrate, this drug was approved in the United States in 1967 for the treatment of hyperlipidemias. Clofibrate can be chemically synthesized by the condensation of phenol with ethyl 2-chloro-2-methylpropionate in the presence of a dehydrochlorinating agent, followed by chlorination and purification. It can also be synthesized by the condensation of p-chlorophenol with acetone and chloroform followed by esterifying the resultant acid to give clofibrate. Clofibrate is a selective agonist of peroxisome proliferator-activated receptor α (PPARα). In a transactivation assay, clofibrate exhibits EC50 values of 50 and 55 μM for murine and human PPARα, respectively. It also binds to PPARγ but with 10-fold less affinity and is inactive at PPARδ at concentrations up to 100 μM. Formulations containing clofibrate have been used to treat dyslipidemia and cardiovascular disease.
• Uses: vasodilator inhibits cholesterol biosynthesis Clofibrate is a lipid-lowering agent (antilipidemic) used for controlling high cholesterol (anticholesteremic) and triacylglyceride levels in the blood. It increases lipoprotein lipase activity to promote the conversion of VLDL to LDL, thereby reducing VLDL levels. It is indicated only in subjects with increased concentrations of VLDL and intermediate-density lipoproteins (IDL) who have failed to respond adequately to gemfibrozil or nicotinic acid. Clofibrate is of limited utility for patients with either familial hypercholesterolemia or polygenic hypercholesterolemia, as comparatively more effective drugs are available for lowering the concentration of LDL in these patients.Clofibrate has no effect on hyperchylomicronemia, nor does it affect concentrations of high-density lipoproteins (HDL). Thus, clofibrate appears to have specific efficacy only in patients with familial type-III hyperlipoproteinemia. There is no substantial evidence proving efficacy of clofibrate in preventing deaths from coronary artery disease. Clofibrate has been used to prevent or control polydipsia, polyuria, and dehydration in a limited number of patients with mild to moderate neurohypophyseal diabetes insipidus. A 5-year multicenter study reported failure of clofibrate in reducing or preventing mortality in cardiovascular disorders, which has provided a setback for the prophylactic use of this drug.
• Therapeutic Function: Antihyperlipidemic
• Clinical Use: Clofibrate is the drug of choice in the treatment of typeIII hyperlipoproteinemias and may also be useful, to a lesserextent, in types IIb and IV hyperlipoproteinemias. The drugis not effective in types I and IIa.Clofibrate can lower plasma concentrations of both triglyceridesand cholesterol, but it has a more consistent clinicaleffect on triglycerides. It also affects lipoprotein plasmalevels by enhancing removal of triglycerides from the circulationand causes reduction of VLDL by stimulatinglipoprotein lipase to increase the catabolism of this lipoproteinto LDL. Clofibrate lowers triglyceride levels in theserum much more than cholesterol levels and decreases levelsof FFAs and phospholipids. The lowering of cholesterollevels may result from more than one mechanism. Clofibrateinhibits the incorporation of acetate into the synthesis ofcholesterol, between the acetate and mevalonate step, by inhibitingsn-glyceryl-3-phosphate acyltransferase. Clofibratealso regulates cholesterol synthesis in the liver by inhibitingmicrosomal reduction of 3-hydroxy-3-methylglutaryl-CoA(HMG-CoA), catalyzed by HMG-CoA reductase. Clofibratemay lower plasma lipids by means other than impairment ofcholesterol biosynthesis, such as increasing excretionthrough the biliary tract.
• Drug interactions: The fibrates potentiate the actions of the coumarin anticoagulants, such as warfarin, so care should be taken to reduce the dose of simultaneously administered anticoagulants, and plasma prothrombin should be frequently measured until the level stabilizes. As mentioned earlier, great care should be given to combining a statin with a fibrate, since this combination may increase the risk of myositis and perhaps rhabdomyolysis.

Technology Process of Clofibrate

There total 11 articles about Clofibrate which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 97.0%

ethyl 2-methyl-2-phenoxypropanoate (18672-04-3) → Clofibrate (637-07-0)

Guidance literature:

With hydrogenchloride; (4s,6s)-2,4,5,6-tetra(9H-carbazol-9-yl)isophthalonitrile; hydrogen bromide; oxygen; In water; acetonitrile; at 25 ℃; for 2.5h; regioselective reaction; Irradiation;

DOI:10.1002/ejoc.201900411

Reference yield: 96.0%

ethyl 2-bromoisobutyrate (600-00-0) + 4-chloro-phenol (106-48-9,82344-39-6) → Clofibrate (637-07-0)

Guidance literature:

With potassium carbonate; In N,N-dimethyl-formamide; at 30 - 70 ℃; for 5h;

Reference yield: 84.0%

→ Clofibrate (637-07-0)

Guidance literature:

With ammonium acetate; acetic acid; at 110 ℃; for 8h;

upstream raw materials:

Clofibric acid

clofibryl chloride

ethyl 2-bromoisobutyrate

4-chloro-phenol

Downstream raw materials:

ethyl 2-methyl-2-phenoxypropanoate

2-(4-cyanophenoxy)-2-methylpropionic acid ethyl ester

ethyl 2-methyl-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]propanoate

Refernces

• 1、 Düsel, Simon Josef Siegfried,K?nig, Burkhard. "Oxidative Photochlorination of Electron-Rich Arenes via in situ Bromination". supporting information. p. 1491 - 1495. Retrieved 2019/04/30.
• 2、 ?a?ewska, Dorota,Kurczab, Rafa?,Wi?cek, Ma?gorzata,Sata?a, Grzegorz,Kie?-Kononowicz, Katarzyna,Handzlik, Jadwiga. "Synthesis and computer-aided analysis of the role of linker for novel ligands of the 5-HT6 serotonin receptor among substituted 1,3,5-triazinylpiperazines". . p. 319 - 325. Retrieved 2018/12/11.