Nebivolol

Base Information

• Chemical Name: Nebivolol
• CAS No.: 99200-09-6
• Deprecated CAS: 104365-59-5
• Molecular Formula: C22H25F2NO4
• Molecular Weight: 405.442
• European Community (EC) Number: 601-527-4
• DSSTox Substance ID: DTXSID9040556
• Nikkaji Number: J33.390E
• Wikipedia: Nebivolol
• Wikidata: Q418130
• NCI Thesaurus Code: C66221
• RXCUI: 31555
• Pharos Ligand ID: 78H9V6NSXZX6
• Metabolomics Workbench ID: 149291
• ChEMBL ID: CHEMBL434394
• Mol file: 99200-09-6.mol

Synonyms:67555, R;alpha,alpha'-(iminobis(methylene))bis(6-fluoro-3,4-dihydro)-2H-1-benzopyran-2-methanol;Bystolic;Hydrochloride, Nebivolol;Lobivon;Nebilet;nebivolol;nebivolol hydrochloride;R 67555;R-67555;R67555;Silostar

Chemical Property of Nebivolol

Chemical Property:

• Appearance/Colour: Odour
• Vapor Pressure: 2.88E-15mmHg at 25°C
• Refractive Index: 1.58
• Boiling Point: 600.455 °C at 760 mmHg
• PKA: 14.29±0.20(Predicted)
• Flash Point: 316.944 °C
• PSA: 70.95000
• Density: 1.31 g/cm³
• LogP: 2.75450
• Storage Temp.: 2-8°C(protect from light)
• XLogP3: 3
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 6
• Exact Mass: 405.17516460
• Heavy Atom Count: 29
• Complexity: 483

Purity/Quality:

Nebivolol ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Drug Classes: Beta-Adrenergic Receptor Antagonists
• Canonical SMILES: C1CC2=C(C=CC(=C2)F)OC1C(CNCC(C3CCC4=C(O3)C=CC(=C4)F)O)O
• Recent ClinicalTrials: Effectiveness and Safety of Combination of Nebivolol and Amlodipine in Hypertensive Patients Versus Each Monotherapy
• Recent EU Clinical Trials: Open-label, multicenter, multinational, interventional Clinical Trial to assess Efficacy and Safety of the extemporaneous combination of Nebivolol and Ramipril in hypertensive patients - ARTEMISIA study
• Description: Nebilet was launched in Germany and the Netherlands as an antihypertensive agent. It is prepared by a five step route starting with 6-fluoro-4- oxobenzopyran-2-carboxylic acid. It is a selective β1-adrenergic receptor antagonist and is 50 times less potent at β2-receptors. Vasodialating properties occur via the nitric oxide pathway. While the L-isomer is more potent than the D-isomer, the racemic mixture is necessary for optimal activity. Upon administration, an immediate fall in blood pressure occurs, it improves both left ventricular systolic and diastolic function, and lowers peripheral blood resistance. Nebilet does not influence insulin sensitivity nor lipid profile comparible to atenolol. Doses of 50 mg of atenolol and 10 mg of Nebilet are equipotent but Nebilet has a longer duration of action due to an accumulation of the drug and increasing plasma levels of active metabolites.
• Uses: Labeled Nebivolol, intended for use as an internal standard for the quantification of Nebivolol by GC- or LC-mass spectrometry.

Technology Process of Nebivolol

There total 26 articles about Nebivolol which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 97.0%

(R*,R*,R*,S*)-N-{2-[(tert-butyldimethylsilyl)oxy]-2-(6-fluoro-3,4-dihydro-2H-2-[1]benzopyranyl)ethyl}-6-fluoro-3,4-dihydro-α-hydroxy-2H-2[1]benzopyran ethanamine → nebivolol (99200-09-6,118457-14-0,118457-15-1,119365-25-2,119365-23-0,1360598-84-0)

Guidance literature:

(R*,R*,R*,S*)-N-{2-[(tert-butyldimethylsilyl)oxy]-2-(6-fluoro-3,4-dihydro-2H-2-[1]benzopyranyl)ethyl}-6-fluoro-3,4-dihydro-α-hydroxy-2H-2[1]benzopyran ethanamine; With hydrogenchloride; methanol; water; at 70 ℃; for 1h;

With sodium hydroxide; In methanol; water;

Reference yield: 90.0%

N-benzyl-(±)-nebivolol → nebivolol (99200-09-6,118457-14-0,118457-15-1,119365-25-2,119365-23-0,1360598-84-0)

Guidance literature:

With 10 wt% Pd(OH)2 on carbon; hydrogen; for 12h; Inert atmosphere; Reflux;

Reference yield: 65.0%

α,α'-[[(phenylmethyl)imino]bismethylene]bis-[6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol] (929706-85-4) → nebivolol (99200-09-6,118457-14-0,118457-15-1,119365-25-2,119365-23-0,1360598-84-0)

Guidance literature:

With hydrogen; palladium on activated charcoal; In 2-methoxy-ethanol; at 20 ℃; normal pressure;

upstream raw materials:

N-[(S,S)-1-hydroxy-2-(6-fluoro-chroman-4-one-2-yl)]-N-[(R,S)-1-hydroxy-2-(6-fiuoro-chroman-4-one-2-yl)]-amine

N-benzyl-N-[(R,R)-1-hydroxy-2-(6-fluoro-chroman-4-one-2-yl)]-N-[(S,R)-1-hydroxy-2-(6-fluoro-chroman-4-one-2-yl)]-amine

(S*,R*)-(±)-α-[(benzylamino)methyl](6-fluoro-2-chromanyl)methanol

dibenzylamine

Downstream raw materials:

(+)-Nebivolol

nebivolol

nebivolol hydrochloride

α,α'-iminobis(methylene)bis[6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol] hydrochloride

Refernces

• 1、 -. "A NEW METHOD FOR PRODUCING NEBIVOLOL HYDROCHLORIDE OF HIGH PURITY". Page/Page column 22. . Retrieved 2015/09/22.
• 2、 -. "PREPARATION OF NEBIVOLOL". Page/Page column 14. . Retrieved 2011/10/19.