503070-58-4

Basic information

• Product Name: Benzeneacetic acid, α,α-diphenyl-, coMpd. with (α1R)-α1-[[[6-[2-[(2,6-dichlorophenyl)Methoxy]ethoxy]hexyl]aMino]Methyl]-4-hydroxy-1,3-benzenediMethanol (1:1)
• Synonyms: Benzeneacetic acid, α,α-diphenyl-, coMpd. with (α1R)-α1-[[[6-[2-[(2,6-dichlorophenyl)Methoxy]ethoxy]hexyl]aMino]Methyl]-4-hydroxy-1,3-benzenediMethanol (1:1);vilanterol trifenatate;GW 642444M;GW642444M;GW-642444M;Vilanterol Trifenatate (API);4-[(R)-2-[[6-[2-(2,6-Dichlorobenzyloxy)ethoxy]hexyl]amino]-1-hydroxyethyl]-2-(hydroxymethyl)phenol triphenylacetate;Vilanterol Trifenate
• CAS NO: 503070-58-4
• Molecular Formula: C₂₀H₁₆O₂*C₂₄H₃₃Cl₂NO₅
• EINECS: -0
• Product Categories: Intermediate
• Mol File: 503070-58-4.mol
• Article Data: 7

Chemical Properties

• Melting Point: 131.9-134.2℃
• Appearance: /
• Storage Temp.: Hygroscopic, -20°C Freezer, Under inert atmosphere
• Solubility: Dichloromethane (Slightly), Methanol (Slightly)
• Stability: Hygroscopic
• CAS DataBase Reference: Benzeneacetic acid, α,α-diphenyl-, coMpd. with (α1R)-α1-[[[6-[2-[(2,6-dichlorophenyl)Methoxy]ethoxy]hexyl]aMino]Methyl]-4-hydroxy-1,3-benzenediMethanol (1:1)(CAS DataBase Reference)
• NIST Chemistry Reference: Benzeneacetic acid, α,α-diphenyl-, coMpd. with (α1R)-α1-[[[6-[2-[(2,6-dichlorophenyl)Methoxy]ethoxy]hexyl]aMino]Methyl]-4-hydroxy-1,3-benzenediMethanol (1:1)(503070-58-4)
• EPA Substance Registry System: Benzeneacetic acid, α,α-diphenyl-, coMpd. with (α1R)-α1-[[[6-[2-[(2,6-dichlorophenyl)Methoxy]ethoxy]hexyl]aMino]Methyl]-4-hydroxy-1,3-benzenediMethanol (1:1)(503070-58-4)

Safety Data

• Hazardous Substances Data: 503070-58-4(Hazardous Substances Data)

Usage

Chemical Properties

Vilanterol trifenatate is a white powder with a molecular weight of 774.8, and the empirical formula is C24H33Cl2NO5.C20H16O2. It insoluble in water and slightly soluble in methanol, ethanol, acetonitrile and propan-2-ol. It is slightly hygroscopic. It is provided in a micronized form.

Uses

Vilanterol Trifenatate is a long-acting β2 adrenergic receptor Agonist with alonger than 24-hour activity in humans, and is being developed to be used in combination with FF. It is also highly selective for the β2-receptor, with over 1000-fold greater selectivity compared to β1-receptors. It demonstrates prolonged bronchodilation in subjects with asthma and COPD.

Preparation

Vilanterol trifenatate is synthesized by incorporation of an oxygen atom at the homobenzylic position of the right-hand side phenyl ring of (R)-salmeterol and has suitable chemical properties for inhaled administration. The combination in fluticasone furoate (FF) and vilanterol trifenatate (VI) in a single inhaler is the first once daily combination available on the market for the treatment of stable COPD.

Definition

ChEBI: Vilanterol Trifenatate is a triphenylacetate salt obtained by combining vilanterol with one equivalent of triphenylacetic acid. Used in combination with fluticasone furoate for treatment of bronchospasm associated with chronic obstructive pulmonary disease. It has a role as a beta-adrenergic agonist and a bronchodilator agent. It contains a vilanterol(1+).

Biological Activity

vilanterol trifenatate is a novel and selective agonist of β2-ar with a pec50 value of 10.37±0.05 [1].vilanterol trifenatate is a novel long-acting β2-ar agonist (laba) with 24h activity in development for inhaled once daily treatment. in the radioligand binding studies, vilanterol trifenatate has shown the binding affinity in the one-affinity site model with pkd values of 9.44±0.07 and 10.82±0.12 in the presence gpp(nh)p and absence gpp(nh)p, respectively. in dissociation studies, vilanterol trifenatate has been reported to bind from the β2-ar with a dissociation t1/2 value of 3.5 min in the presence of gpp(nh)p. vilanterol trifenatate has been found to have a good selectivity for β2-ar over the other β-ar receptor subtypes(β1and β3) with pec50 values of 10.37±0.05, 6.98±0.03 and 7.36±0.03, respectively. vilanterol trifenatate has exhibited at least 1000-fold selectivity over both β1-and β3-ar subtypes [1].

Dosage

The recommended and maximum dose is one inhalation of vilanterol trifenatate 25 micrograms once daily either morning or evening but at the same time every day.

Mode of action

Vilanterol Trifenatate is a selective long-acting beta2-receptor agonist (also referred to as a LABA). The pharmacologic effects of beta2-adrenoceptor agonist drugs, including vilanterol trifenatate, are at least in part attributable to stimulation of intracellular adenylate cyclase, the enzyme that catalyses the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cyclic AMP). Increased cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells.

Upstream product

• 503068-34-6 4-[(1R)-2-({6-[(2-{[(2,6-dichlorophenyl)methyl]oxy}ethyl)oxy]-hexyl}-amino)-1-hydroxyethyl]-2-(hydroxymethyl)phenol 
• 595-91-5 triphenylacetic acid 
• 503068-37-9 (2R)-hydroxy-2-(2,2-dimethyl-4Η-1,3-benzodioxole-6-yl)-N-3-[6-[2-[(2,6-dichlorophenyl)methoxy]ethoxy]hexyl]-ethylamine 
• 102293-80-1 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone 
• 743460-69-7 (R)-(2-bromo-1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)ethoxy)(tert-butyl)dimethylsilane 
• 503070-57-3 2-((2-((6-bromohexyl)oxy)ethoxy)methyl)-1,3-dichlorobenzene 
• 452339-73-0 (5R)-5-(2,2-dimethyl- 4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one 
• 503068-36-8 (5R)-3-{6-[(2-{[(2,6-dichlorophenyl)methyl]oxy}ethyl)oxy]-hexyl}-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one 
• 15258-73-8 2,6-dichlorobenzyl alcohol 
• 20443-98-5 2,6-Dichlorobenzyl bromide 

Relevant articles and documents

Enantiomeric separation of vilanterol trifenatate by chiral liquid chromatography

Vilanterol trifenatate is a novel chiral long-acting β2-agonist developed. Vilanterol combined with inhaled corticosteroids can treat COPD and asthma. A simple liquid chromatographic method is developed for the quantitative determination of R-vilanterol and S-vilanterol (impurity S). HPLC separation was achieved on Chiralpak ID (250?×?4.6?mm; particle size 5?μm) column using hexane-ethanol-ethanolamine (75:25:0.1, v/v/v) as mobile phase at a flow rate of 1.0?mL/min. The resolution is greater than 3.3. Ethanolamine in the mobile phase is vital to enhance chromatographic efficiency and resolution between the isomers. The method was validated with respect to accuracy, specificity, precision, LOD, LOQ, linearity, and robustness as ICH guidelines.

AN IMPROVED PROCESS FOR PREPARATION OF VILANTEROL OR A PHARMACEUTICALLY ACCEPTABLE SALT THEREOF

The invention discloses an improved process for preparation of Vilanterol or a pharmaceutically acceptable salt thereof with good yields and high purity.

Vilanterol triphenylacetic acid salt crystallization method

The invention discloses a Vilanterol triphenylacetic acid salt crystallization method, and belongs to the field of drug synthesis. According to the method, Vilanterol triphenylacetic acid salt is crystallized by a gradient cooling method in chlorinated hydrocarbon and low-alcohol mixed solvents. By the aid of the crystallization method, reaction yield and chemical purity are improved.