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Clofibrate

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Clofibrate Basic information

Product Name:
Clofibrate
CAS:
637-07-0
MF:
C12H15ClO3
MW:
242.7
EINECS:
211-277-4
Mol File:
637-07-0.mol
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Clofibrate Chemical Properties

Melting point:
<25 °C
Boiling point:
154 °C
Density 
1.14 g/mL at 25 °C(lit.)
refractive index 
n20/D 1.503
Flash point:
113 °C
storage temp. 
2-8°C
solubility 
Soluble to 100 mM in DMSO.
form 
liquid
color 
clear, colorless
Water Solubility 
97.08mg/L(room temperature)
Merck 
14,2377
BRN 
1913459
CAS DataBase Reference
637-07-0(CAS DataBase Reference)
NIST Chemistry Reference
Clofibrate(637-07-0)
EPA Substance Registry System
Clofibrate (637-07-0)
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Safety Information

Hazard Codes 
Xn,N
Risk Statements 
22-37/38-41-51/53-40
Safety Statements 
26-36/37/39-61-45-36/37
RIDADR 
UN 3082 9/PG 3
WGK Germany 
3
RTECS 
UE9480000
HazardClass 
9
HS Code 
29189900
Hazardous Substances Data
637-07-0(Hazardous Substances Data)
Toxicity
LD50 in mice, rats (g/kg): 1.28, 1.65 orally (Metz)

MSDS

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Clofibrate Usage And Synthesis

Chemical Properties

Clear Colorless Oil

Uses

vasodilator

Uses

inhibits cholesterol biosynthesis

Uses

Antilipemic

Definition

ChEBI: The ethyl ester of clofibric acid.

brand name

Atromid (Wyeth);Aatroayerst;Aitiflus;Angiocapsul;Arterioflexion;Artriosan;Asa/cpib;Aterioplexin;Ateroayrest;Ateroclar;Aterofront;Ateronlen;Aterosol;Atevil;Atheroayerst;Atrofort;Atrolan;Atromid-s;Atrom-s;Ay 61;Biocleran;Clareden;Cloberab;Clobrate;Clobren-5 f;Clofenit;Clofibral;Clofibrate ayerst;Clofibrate compose;Clofibrato ayerst;Clofibrato procaps;Clofibrem;Clofimide;Clofin-icn;Clofipront 5000;Clofirem;Clofirin;Clofi-t;Clopin;Col 180;Contra-lipide;Corafen;Cr/085;Dabical;Dilectus;Doctus;Duplinal;Duraclofibrate;Ellemger;Eramid;Fibramid;Fibrolynt;Geri-70;Geromid;Healthstyle;Ici 28257nt;Ipolipid;Kontalipide;Levatram;Liapten;Liparil;Lipaten;Lipavlon 500;Lipicidon;Lipidicon;Liporan;Liptrinal;Lostat;Neoatromid;Nibratal;Nibratol;Nnormet;Nobret;Norinolipol;Normet richter;Nosterolin;Novofibrate;Omelip;Provasa;Recade;Regelan n 500;Sclerovasal;Serolipid;Sinteroid;Sklerocip;Sklerolip;Sklerovasal;Supraoxid;Tepincal;Tepingal;Vimedel;Vocaline.

World Health Organization (WHO)

Clofibrate, an antihyperlipidaemic agent, was introduced in 1967 and was subsequently extensively studied in the primary and secondary prevention of ischaemic heart disease. Following reports, published in 1978, of increased mortality among patients receiving clofibrate in a WHO-sponsored cooperative trial concerned with the primary prevention of ischaemic heart disease, the drug was withdrawn in some countries and its approved indications were severely restricted in many others. These restrictions have become the norm for more recently developed analogues of clofibrate. (Reference: (WHODI) WHO Drug Information, 2, 6, 1979)

General Description

Clofibrate, ethyl 2-(p-chlorophenoxy)-2-methylpropionate (Atromid-S), is a stable, colorless topale yellow liquid with a faint odor and a characteristictaste. It is soluble in organic solvents but insoluble in water.
Clofibrate is prepared by a Williamson synthesis, condensingp-chlorophenol with ethyl -bromoisobutyrate, or bythe interaction of a mixture of acetone, p-chlorophenol, andchloroform in the presence of excess potassium hydroxide.The acid obtained by either of these methods is esterified togive clofibrate. Both acid and ester are active; the latter, however,is preferred for medicinal use. Clofibrate is hydrolyzedrapidly to 2-p-chlorophenoxy-2-methylpropionic acid by esterasesin vivo and, bound to serum albumin, circulates inblood. The acid has been investigated as a hypolipidemicagent. It is absorbed more slowly and to a smaller extent thanis the ester. The aluminum salt of the acid gives even lowerblood levels than p-chlorophenoxy-2-methylpropionic acid.

Hazard

Questionable carcinogen; toxic; causes nausea, vomiting, diarrhea, weakness, stiffness, cramps, and muscle tenderness.

Biological Activity

PPAR agonist (EC 50 values are 50, 500 and > 100 μ M at PPAR α , PPAR γ and PPAR δ respectively). Antihyperlipoproteinemic.

Mechanism of action

The three structurally related fibrates available in the United States are gemfibrozil (Lopid), fenofibrate (Tricor) and clofibrate (Atromid-S).They share common uses and toxicities. The fibrates typically lower VLDL triglyceride by 40% or more and elevate plasma HDL cholesterol by 10 to 15%. The reduction of plasma triglycerides in humans appears due to increased lipoprotein lipase (LPL) activity. The fibrates activate a nuclear receptor (transcription factor) termed peroxisomal proliferation activated receptor (PPAR) that is a member of the steroid hormone receptor superfamily. PPAR increases transcription of the LPL gene and decreases transcription of the apolipoprotein CIII gene (apo CIII). Since LPL is responsible for catabolism of VLDL triglyceride and apo CIII is an inhibitor of LPL activity, the combined consequences of these changes are increased LPL activity and enhanced removal of triglyceride from the circulation.
The elevation of HDL levels by fibrates may be due to two drug actions: induced synthesis of apo-A1, the principal apoprotein of HDL, and increased assembly of new HDL particles in the circulation. Surface components of VLDL contribute to formation of HDL, as the VLDL particles are reduced in size through the action of LPL.The increased rate of catabolism of VLDL caused by the fibrates would provide more components for assembly of HDL particles.

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.

Side effects

The fibrates are generally well tolerated, with GI distress being the most likely complaint. Other adverse effects include myositis and erectile dysfunction, particularly with clofibrate. There is ongoing concern about the fibrates increasing the risk of gallstones, although the extent of risk is unclear. Because clofibrate was associated with increased mortality in early clinical trials, it should be considered as a second-line drug.

Safety Profile

Poison by intravenous route.Moderately toxic by ingestion and other routes. Anexperimental teratogen. Other experimental reproductiveeffects. Reduces plasma lipid levels. Human systemiceffects by ingestion: muscle weakness, muscle spasms, andfever. Q

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.

Clofibrate Preparation Products And Raw materials

Raw materials

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ClofibrateSupplierMore

J & K SCIENTIFIC LTD.
Tel:
010-82848833- ;010-82848833-
Email:
jkinfo@jkchemical.com;market6@jkchemical.com
Meryer (Shanghai) Chemical Technology Co., Ltd.
Tel:
21-61259100-
Email:
sh@meryer.com
3B Pharmachem (Wuhan) International Co.,Ltd.
Tel:
821-50328103-801
Email:
3bsc@sina.com
TCI (Shanghai) Development Co., Ltd.
Tel:
021-67121386 / 800-988-0390
Email:
Sales-CN@TCIchemicals.com
Energy Chemical
Tel:
021-58432009
Email:
sales8178@energy-chemical.com
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