41859-67-0 Usage
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
Different sources of media describe the Uses of 41859-67-0 differently. You can refer to the following data:
1. Antilipemic
2. antihyperlipidemic
3. Bezafibrate has been used:a supplement in the standard diet (SD)?for mice to study its effect on diabetesto evaluate its effect on hepatitis C virus (HCV) assembly and secretionto evaluate its effect on gonadal steroidogenesis and?spermatogenesis?of zebrafish and also used as standard for HPLC
Manufacturing Process
0.292 moles p-chlorobenzoyl chloride and 50 ml dry pyridine were added
dropwise to 0.146 moles tyramine in 60 ml dry pyridine for 10 minutes. Then
the mixture was poured in about 500 g of ice with water. The fallen-out
crystals was filtered off, washed with diluted HCl, water and NaHCO3 solution
and 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 N
KOH and heated at 40°-45°C for 1 hour. On cooling 130 ml 2 N HCl was
added. The fallen-out precipitate was filtered off, filtrate was distilled off to
dryness. The residue was washed with water, NaHCO3 solution and
recrystallized 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 with
0.93 mole N-(4-chlorobenzoyl)tyramine. Methanol was removed in vacuum to
dryness. The residue was slurried in 100 ml absolute toluene and 0.137 moles
2-bromo-2-methylpropionic acid ethyl ester was added. The suspension was
heated for 25 hours at 80°C. Then it was distilled in vacuum to dryness and
the residue was dissolved in CH2Cl2, washed with diluted HCl, NaOH and
water, and dried over CaCl2. On removing of the solvent, the crude 2-{4-[2-
(4-chlorobenzoylamino)ethyl]phenoxy}-2-methylpropionic acid ethyl ester was
obtained. 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 N
KOH at ambient temperature and stood for 2 hours, then it was heated at
40°C for 1 hour. The substance was dissolved completely. On cooling the
mixture was neutralized with 200 ml 1 N HCl. The solvents were removed in
vacuum. The residue was washed with water and recrystallized from acetone
to give 2-{4-[2-(4-chlorobenzoylamino)ethyl]phenoxy}-2-methylpropionic
acid; 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.
Check Digit Verification of cas no
The CAS Registry Mumber 41859-67-0 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 4,1,8,5 and 9 respectively; the second part has 2 digits, 6 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 41859-67:
(7*4)+(6*1)+(5*8)+(4*5)+(3*9)+(2*6)+(1*7)=140
140 % 10 = 0
So 41859-67-0 is a valid CAS Registry Number.
InChI:InChI=1/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)
41859-67-0Relevant articles and documents
Amide Bond Formation via the Rearrangement of Nitrile Imines Derived from N-2-Nitrophenyl Hydrazonyl Bromides
Boyle, Mhairi,Livingstone, Keith,Henry, Martyn C.,Elwood, Jessica M. L.,Lopez-Fernandez, J. Daniel,Jamieson, Craig
, p. 334 - 338 (2022/01/20)
We report how the rearrangement of highly reactive nitrile imines derived from N-2-nitrophenyl hydrazonyl bromides can be harnessed for the facile construction of amide bonds. This amidation reaction was found to be widely applicable to the synthesis of primary, secondary, and tertiary amides and was used as the key step in the synthesis of the lipid-lowering agent bezafibrate. The orthogonality and functional group tolerance of this approach was exemplified by the N-acylation of unprotected amino acids.
Preparation process of bezafibrate compound
-
, (2018/10/19)
The invention especially relates to preparation technology for a bezafibrate compound, belonging to the field of pharmaceutical synthesis. The invention provides a preparation process of the bezafibrate compound. The preparation process comprises the following steps: subjecting a compound with a structure as shown in a formula a or a' and a compound with a structure as shown in a formula b to an acylation reaction in an aqueous solution of inorganic base B so as to obtain a bezafibrate intermediate with a structure as shown in a formula c; and then subjecting the bezafibrate intermediate, R1COR2 and methyl halide to a condensation reaction in an aqueous solution of inorganic alkali A to obtain the bezafibrate compound with a structure as shown in a formula d, wherein process flow is as described in the specification, M is a water-soluble inorganic acid, X is a halogen or alkoxy group, and R1 and R2 are the same or different and are selected from a group consisting of H and C1-C3 alkylgroups.
Treatment of skin conditions by use of PPAR alpha activators
-
, (2008/06/13)
Disorders of the skin and mucous membrane that have a disrupted or dysfunctional epidermal barrier are treated or prevented by topical application of compounds that are either activators of the farnesoid X receptor, activators of the peroxisome proliferator-activated receptor alpha , and oxysterol activators of the LXR alpha receptor. The same compounds are also effective in treating disorders of epidermal differentiation and proliferation.
