23288-49-5

Basic information

• Product Name: Probucol
• Synonyms: PROBUCOL;4,4’-((1-methylethylidene)bis(thio))bis(2,6-bis(1,1-dimethylethyl)-pheno;biphenabid;bisbid;bisphenabid;dh581;4,4'-ISOPROPYLIDINEDITHIO-BIS-(2,6-DI-TERT-BUTYL)PHENOL;4-({1-[(4-hydroxy-3,5-di-t-butylphenyl)thio]-1-methylethyl}thio)-2,6-di-t-butylphenol
• CAS NO: 23288-49-5
• Molecular Formula: C₃₁H₄₈O₂S₂
• Molecular Weight: 516.84
• EINECS: 245-560-9
• Product Categories: Cardiovascular;Aromatics;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds;API;LORELCO;Isolabel;Cardiovascular APIs
• Mol File: 23288-49-5.mol
• Article Data: 12

Chemical Properties

• Melting Point: 126-128°C
• Boiling Point: 571.58°C (rough estimate)
• Flash Point: 264.9 °C
• Appearance: White Solid
• Density: 1.0008 (rough estimate)
• Vapor Pressure: 1.46E-12mmHg at 25°C
• Refractive Index: 1.5341 (estimate)
• Storage Temp.: Desiccate at +4°C
• Solubility: Chloroform (Slightly), Ethyl Acetate (Slightly)
• PKA: 10.27±0.70(Predicted)
• Merck: 14,7755
• CAS DataBase Reference: Probucol(CAS DataBase Reference)
• NIST Chemistry Reference: Probucol(23288-49-5)
• EPA Substance Registry System: Probucol(23288-49-5)

Safety Data

• WGK Germany: 2
• RTECS: AL3705000
• Hazardous Substances Data: 23288-49-5(Hazardous Substances Data)

Usage

Description

Probucol is a kind of bis-phenol antioxidant with anti-hyperlipidemic activity. It had been initially developed for the treatment of coronary artery disease. However, its clinical trials were stopped after people found that it could lower the HDL and LDL cholesterol in patients of a history of heart disease. Probucol exerts its effect through accelerating the fractional rate of low-density (LDL) catabolism which is in the final pathway of cholesterol elimination inside the body. It may also inhibit the early stage of cholesterol biosynthesis and dietary cholesterol absorption.

References

https://www.drugbank.ca/drugs/DB01599 https://pubchem.ncbi.nlm.nih.gov/compound/probucol#section=Top https://en.wikipedia.org/wiki/Probucol

Chemical Properties

White Solid

Uses

Different sources of media describe the Uses of 23288-49-5 differently. You can refer to the following data:
1. antihyperlipidemic
2. Probucol is an antilipemic.
3. anti-hyperlipoproteinemic
4. An antioxidant, anti-inflammatory, and hypocholesterolemic agent which inhibits atherogenesis in murine models.

Definition

ChEBI: A dithioketal that is propane-2,2-dithiol in which the hydrogens attached to both sulfur atoms are replaced by 3,5-di-tert-butyl-4-hydroxyphenyl groups. An anticholesteremic drug with antioxidant and anti-inflammatory properties, it is used to treat high l vels of cholesterol in blood.

Brand name

Lorelco (Sanofi Aventis).

Biological Functions

Probucol (Lorelco) is a hypocholesterolemic drug with few side effects that modestly (15–30%) decreases elevated plasma LDL cholesterol levels. The marginal LDL-lowering action plus reports that it can lower HDL cholesterol resulted in its discontinuation as a hypocholesterolemic drug. However, it still may reduce the risk of CHD because it is a powerful antioxidant. The oxidation hypothesis of atherosclerosis states that oxidation of lipids in LDL is required for LDL uptake by macrophages and smooth muscle cells in the intima of arteries, leading to their transformation to foam cells, an early event in atherogenesis. A recent clinical trial reported that use of probucol decreased the rate of restenosis of coronary arteries by 50% in patients who underwent angioplasty. Fluvastatin also has potent antioxidant properties that may contribute to its antiatherosclerotic effects.These findings suggest that reducing high plasma lipids may not be the only approach to retarding the progression of atherosclerosis and decreasing the risk of coronary heart disease.

General Description

Probucol, 4,4＇ -[(1-methylethylidene)bis(thio)]bis[2,6-bis(1,1-dimethylethyl)phenol], DH-581(Lorelco), is a chemical agent that was developed for the plasticsand rubber industry in the 1960s. The probucol moleculehas two tertiary butylphenol groups linked by a dithiopropylidenebridge, giving it a high lipophilic character with strongantioxidant properties. In humans, it causes reduction of bothliver and serum cholesterol levels, but it does not alter plasmatriglycerides. It reduces LDL and (to a lesser extent) HDLlevels by a unique mechanism that is still not clearly delineated.The reduction of HDL may be caused by the ability ofprobucol to inhibit the synthesis of apoprotein A-1, a majorprotein component of HDL. It is effective at reducing levelsof LDL and is used in hyperlipoproteinemias characterized byelevated LDL levels.

Biological Activity

Antioxidant, anti-inflammatory and hypocholesterolemic agent. Inhibits atherogenesis in genetically hypercholesterolemic rabbits (Watanabe) and attenuates ischemia/reperfusion-induced cardiomyocyte apoptosis.

Mechanism of action

Probucol reduces the overall level of cholesterol—primarily low-density lipoproteins— without having an effect on triglycerides and very low-density lipoproteins. It has been suggested that it inhibits synthesis of cholesterol itself and increases removal of bile salts. Upon using this drug, a fraction of low-density proteins is reduced; however, even more significant is the reduction of high-density proteins. From the epidemiological point of view, this is dangerous, because lowering the concentration of high-density proteins means less cholesterol is removed from tissues. However, in any case, probucol lowers the level of cholesterol in the plasma by 10–15%. Moreover, it has been shown that probucol facilitates reduction of necrotic zones in myocardial ischemia.

Pharmacology

Being a lipophilic compound, it is easily distributed into fatty tissue and, as a result, approximately 20% of its maximum concentration in the blood is still maintained for 6 months.

Synthesis

Probucol, bis(3,5-tert-butyl-4-hydroxyphenyl)mercaptol acetone (20.2.6), is synthesized by thioketalizing acetone with 2,6-di-tert-butyl-4-mercaptophenol in the presence of hydrogen chloride.

InChI:InChI=1/C31H48O2S2/c1-27(2,3)21-15-19(16-22(25(21)32)28(4,5)6)34-31(13,14)35-20-17-23(29(7,8)9)26(33)24(18-20)30(10,11)12/h15-18,32-33H,1-14H3

Upstream product

• 950-59-4 4-hydroxy-3,5-di-tert-butylthiophenol 
• 67-64-1 acetone 

Downstream Products

• 6386-58-9 4,4'-dithiobis(2,6-di-tert-butylphenol) 
• 6386-61-4 bis(4-hydroxy-3,5-di-tert-butylphenyl) trisulfide 
• 719-22-2 2,6-Di-tert-butyl-1,4-benzoquinone 
• 366494-63-5 5-O-{2,6-di-tert-butyl-4-[1-(3,5-di-tert-butyl-4-hydroxy-phenylsulfanyl)-1-methyl-ethylsulfanyl]phenyl}-2,3-O-(ethoxymethylene)-D-ribonic acid γ-lactone 
• 870460-21-2 2,6-di-tert-butyl-4-{1-[3,5-di-tert-butyl-4-(2-ethoxy-5(R)-hydroxymethyl-[1,3]dioxolan-4(R)-ylmethoxy)-phenylsulfanyl]-1-methyl-ethylsulfanyl}-phenol 
• 488-82-4 D-Arabitol 
• 50-69-1 D-ribose 
• 216168-57-9 {2,6-di-tert-butyl-4-[1-(3,5-di-tert-butyl-4-hydroxyphenylsulfanyl)-1-methylethylsulfanyl]phenoxy}acetic acid ethyl ester 
• 870460-32-5 2,6-di-tert-butyl-4-(1-{3,5-di-tert-butyl-4-[2-(2,2-dimethyl-[1,3]dioxolan-4(S)-yl)-ethoxy]-phenylsulfanyl}-1-methyl-ethylsulfanyl)-phenol 
• 870460-36-9 2,6-di-tert-butyl-4-[1-(3,5-di-tert-butyl-4-{2-[2-ethoxy-5-(2-hydroxy-ethyl)-[1,3]dioxolan-4-yl]-ethoxy}-phenylsulfanyl)-1-methyl-ethylsulfanyl]-phenol 
• 216167-92-9 2-[4-[[1-[[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]thio]-1-methylethyl]thio]-2,6-bis(1,1-dimethylethyl)phenoxy]acetic acid 

Relevant articles and documents

METHODS FOR PRODUCING 2,6-DI-TERT-BUTYL-4-MERCAPTOPHENOL AND 4,4'-ISOPROPYLIDENEDITHIOBIS[2,6-DI-TERT-BUTYLPHENOL]

The present invention provides a method for producing 2,6-di-tert-butyl-4-mercaptophenol containing reducing bis(3,5-di-tert-butyl-4-hydroxyphenyl) polysulfide with zinc in a mixed solvent of toluene and n-butanol, and provides a method for producing 4,4'-isopropylidenedithiobis[2,6-di-tert-butylphenol] using the above-mentioned method.

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