1044870-39-4

Basic information

• Product Name: RVX-208
• Synonyms: 2-(4-(2-hydroxyethoxy)-3,5-diMethylphenyl)-5,7-diMethoxyquinazolin-4(3H)-one;RVX-208;RVX-000222;4(3H)-Quinazolinone, 2-[4-(2-hydroxyethoxy)-3,5-dimethylphenyl]-5,7-dimethoxy-;2-[4-(2-hydroxyethoxy)-3,5-dimethylphenyl]-5,7-dimethoxy-4(3H)-quinazolinone RVX-208;Apabetalone;Apabetalone-RVX-208;RVX-208(RVX000222)
• CAS NO: 1044870-39-4
• Molecular Formula: C₂₀H₂₂N₂O₅
• Molecular Weight: 370.39908
• Product Categories: Inhibitors
• Mol File: 1044870-39-4.mol
• Article Data: 12

Chemical Properties

• Boiling Point: 594.2±60.0 °C(Predicted)
• Appearance: /
• Density: 1.28±0.1 g/cm3(Predicted)
• Storage Temp.: -20°C (des.)
• Solubility: Soluble in DMSO (up to 75 mg/ml) or in Ethanol (up to 4 mg/ml).
• PKA: 14.21±0.10(Predicted)
• Stability: Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 1 month.
• CAS DataBase Reference: RVX-208(CAS DataBase Reference)
• NIST Chemistry Reference: RVX-208(1044870-39-4)
• EPA Substance Registry System: RVX-208(1044870-39-4)

Safety Data

• Hazardous Substances Data: 1044870-39-4(Hazardous Substances Data)

Usage

Description

RVX-208 is a selective antagonist of bromodomain and extra terminal (BET) proteins' bromodomains, which play a crucial role in gene transcription by interacting with acetylated lysine-containing sequences on target proteins. It exhibits a higher affinity for the second bromodomain (BD2) compared to the first bromodomain (BD1) and is capable of selectively releasing BET proteins from chromatin in cells. RVX-208 has been shown to interfere with the BET protein BRD4, leading to increased expression of apolipoprotein (Apo) A1 and reducing atherosclerosis in hyperlipidemic ApoE-deficient mice.

Uses

Used in Pharmaceutical Industry:
RVX-208 is used as a therapeutic agent for targeting BET proteins, particularly for the treatment of various diseases and conditions associated with altered gene transcription and chromatin remodeling. Its ability to selectively release BET proteins from chromatin and interfere with BRD4 makes it a promising candidate for developing novel treatments.
Used in Cardiovascular Disease Management:
RVX-208 is used as a potential treatment for atherosclerosis, particularly in hyperlipidemic ApoE-deficient mice. Its capacity to reduce atherosclerosis and increase the expression of apolipoprotein A1 suggests that it may have beneficial effects on cardiovascular health and disease prevention.
Used in Gene Regulation Research:
RVX-208 is used as a research tool for studying the role of BET proteins and their bromodomains in gene transcription and chromatin remodeling. Its selectivity for BD2 over BD1 allows researchers to investigate the specific functions and interactions of these bromodomains in various cellular processes and diseases.

References

1) Picaud?et al. (2013),?RVX-208, an inhibitor of BET transcriptional regulators with selectivity for the second bromodomain; Proc. Natl. Acad. Sci. USA,?110?19754 2) McLure?et al. (2013),?RVX-208, an inducer of ApoA-I in humans, is a BET bromodomain antagonist; PLoS One,?8e83190 3) Bailey?et al. (2010),?RVX-208: a small molecule that increases apolipoprotein A-I and high-density lipoprotein cholesterol in vitro and in vivo; J. Am. Coll. Cardiol.,?55?2580 4) Jahagirdar?et al. (2014),?A novel BET bromodomain inhibitor, RVX-208 shows reduction of atherosclerosis in hyperlipidemic ApoE deficient mice; Atherosclerosis,?236?91

Upstream product

• 1039948-89-4 4-(2-hydroxy ethoxy)-3,5-dimethyl benzaldehyde 
• 63920-73-0 2-amino-4,6-dimethoxybenzamide 
• 1044872-73-2 4-[2-(tert-butyldimethylsilanyloxy)ethoxy]-3,5-dimethylbenzaldehyde 
• 21544-81-0 4,6-dimethoxyindoline-2,3-dione 
• 2233-18-3 4-hydroxy-3,5-dimethylbenzaldehyde 
• 40891-33-6 3,5-dimethoxyaniline hydrochloride 
• 10272-07-8 3.5-dimethoxyaniline 
• 1545025-44-2 2-amino-4,6-dimethoxybenzonitrile 
• 2735-04-8 2,4-Dimethoxyaniline 
• 62827-49-0 2-bromo-4,6-dimethoxybenzoic acid 
• 96-49-1 [1,3]-dioxolan-2-one 
• 1044870-30-5 2-(4-hydroxy-3,5-dimethylphenyl)-5,7-dimethoxy-3,4-dihydroquinazolin-4-one 
• 81574-69-8 2-bromo-4,6-dimethoxybenzaldehyde 
• 20469-65-2 1-bromo-3,5-dimethoxybenzene 

Downstream Products

• 1044871-58-0 propylcarbamic acid-2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl ester 
• 1044871-64-8 cyclohexylcarbamic acid-2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl ester 
• 1246250-66-7 3-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)-5-phenylimidazolidine-2,4-dione 
• 1253733-29-7 N-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)-N-methylformamide 
• 1253733-25-3 N-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl)-N-methylacetamide 
• 1202407-32-6 2-(3,5-dimethyl-4-(2-(methylamino)ethoxy)phenyl)-5,7-dimethoxyquinazolin-4(3H)-one 
• 1044870-92-9 2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)acetic acid 
• 1444000-04-7 3,4,5-triacetoxy-6-(2-(4-(3-(2,2-dimethylpropionyloxymethyl)-5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethoxy)tetrahydropyran-2-carboxylic acid methyl ester 
• 1444000-02-5 6-(2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethoxy)-3,4,5-trihydroxytetrahydropyran-2-carboxylic acid 
• 1444000-03-6 2,2-dimethylpropionic acid 2-(4-(2-hydroxyethoxy)-3,5-dimethylphenyl)-5,7-dimethoxy-4-oxo-4H-quinazolin-3-ylmethyl ester 
• 1202407-33-7 2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl 4-fluoro-phenylcarbamate 
• 1202407-34-8 2-(4-(5,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-yl)-2,6-dimethylphenoxy)ethyl methanesulfonate 

Relevant articles and documents

Discovery of Orally Bioavailable Chromone Derivatives as Potent and Selective BRD4 Inhibitors: Scaffold Hopping, Optimization, and Pharmacological Evaluation

Bromodomain-containing protein 4 (BRD4) represents a promising drug target for anti-inflammatory therapeutics. Herein, we report the design, synthesis, and pharmacological evaluation of novel chromone derivatives via scaffold hopping to discover a new class of orally bioavailable BRD4-selective inhibitors. Two potent BRD4 bromodomain 1 (BD1)-selective inhibitors 44 (ZL0513) and 45 (ZL0516) have been discovered with high binding affinity (IC50 values of 67-84 nM) and good selectivity over other BRD family proteins and distant BD-containing proteins. Both compounds significantly inhibited the expression of Toll-like receptor-induced inflammatory genes in vitro and airway inflammation in murine models. The cocrystal structure of 45 in complex with human BRD4 BD1 at a high resolution of 2.0 ? has been solved, offering a solid structural basis for its binding validation and further structure-based optimization. These BRD4 BD1 inhibitors demonstrated impressive in vivo efficacy and overall promising pharmacokinetic properties, indicating their therapeutic potential for the treatment of inflammatory diseases.

Design, synthesis and biological evaluation of hypolipidemic compounds based on BRD4 inhibitor RVX-208

Bromodomain-containing protein 4 (BRD4) is a new therapeutic target for the treatment of diseases including cardiovascular diseases, cancer, inflammation and central nervous system (CNS) disorders. In this study, we introduced the pharmacophore of fibrates to a BRD4 inhibitor, RVX-208, to design dual-active hypolipidemic compounds, and found that some of new analogues showed favorable hypolipidemic activities. Synthetic accessibility towards this class of compounds optimized RVX-208 as well as would supply more thoughts on hypolipidemic drugs.

Preparation method for Apabetalone

The invention relates to a preparation method for Apabetalone, and particularly discloses a synthesis method for Apabetalone. The preparation method comprises the following steps: (1) a first intermediate, i.e., 2-bromo-4,6-dimethoxy benzamide, is prepared; (2) a second intermediate, i.e., 4-{2-[(t-butyldimethylsilicon)oxy]ethyoxyl}-3,5-dimethyl benzaldehyde, is prepared; (3) the first intermediate and the second intermediate are sealed under the conditions of cuprous bromide, cesium carbonate, L-proline and ammonia hydroxide to react, so that Apabetalone is obtained. The preparation method disclosed by the invention is simple, and yield is high.