Levonebivolol

Base Information

• Chemical Name: Levonebivolol
• CAS No.: 118457-14-0
• Molecular Formula: C₂₂H₂₅F₂NO₄
• Molecular Weight: 405.442
• European Community (EC) Number: 601-527-4
• UNII: GMK2E335DQ
• Nikkaji Number: J330.677A
• Wikidata: Q27132969
• NCI Thesaurus Code: C91033
• Metabolomics Workbench ID: 63091
• ChEMBL ID: CHEMBL2365658
• Mol file: 118457-14-0.mol

Synonyms:Levonebivolol;118457-16-2;l-nebivolol;(-)-Nebivolol;Levonebivolol [INN];UNII-GMK2E335DQ;118457-14-0;(-)-SSSR-nebivolol;(R,S,S,S)-nebivolol;R 67145;GMK2E335DQ;Bystolic;CHEBI:64020;Vasoxen;Nebivolol Impurity A;(1S,1'S)-2,2'-iminobis{1-[(2R,2'S)-6-fluoro-3,4-dihydro-2H-chromen-2-yl]ethanol};(S)-1-((R)-6-fluorochroman-2-yl)-2-(((S)-2-((S)-6-fluorochroman-2-yl)-2-hydroxyethyl)amino)ethan-1-ol;[2R,alphaS,2'S,alpha'S]-alpha,alpha'-[imino-bis(methylene)]bis[6-fluoro-3,4-dehydro-2H-1-benzopyran-2-methanol];Nebivolol (USAN/INN);R-67145;rel-Nebivolol;(1S)-1-[(2S)-6-fluoro-3,4-dihydro-2H-chromen-2-yl]-2-[[(2S)-2-[(2R)-6-fluoro-3,4-dihydro-2H-chromen-2-yl]-2-hydroxyethyl]amino]ethanol;l-Nebivolol;alpha,alpha'-(iminodi-methylene)bis[6-fluoro-2-chromanmethanol];LEVONEBIVOLOL [WHO-DD];SCHEMBL7919700;CHEMBL2365658;KOHIRBRYDXPAMZ-YHDSQAASSA-N;HMS3886O20;(alpha R,-alpha'R,2R,2'S)-rel-alpha,-alpha'-[Iminobis(methylene)]bis[6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol];HY-B0203;s5739;AKOS040752538;AT27091;CS-O-31133;D05127;R67145;Q27132969;(+/-)[R*,S*,S*,S*]-alpha,alpha'-[imino-bis (methylene)] bis [6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol];(|AS,|A inverted exclamation markaS,2R,2 inverted exclamation markaS)-|A,|A inverted exclamation marka-[Iminobis(methylene)]bis[6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol];(1S)-2-(((2S)-2-((2R)-6-FLUORO-3,4-DIHYDRO-2H-CHROMEN-2-YL)-2-HYDROXYETHYL)AMINO)-1-((2S)-6-FLUORO-3,4-DIHYDRO-2H-CHROMEN-2-YL)ETHANOL;2H-1-Benzopyran-2-methanol, alpha,alpha'-(iminobis(methylene))bis(6-fluoro-3,4-dihydro-, (2S-(2R*(R*(R*(S*)))))-

Chemical Property of Levonebivolol

Chemical Property:

• Vapor Pressure: 2.88E-15mmHg at 25°C
• Boiling Point: 600.5°C at 760 mmHg
• PKA: pKa 8.22(H2O,t =25±1,Iundefined,Ar) (Uncertain)
• Flash Point: 316.9°C
• PSA: 100.62000
• Density: 1.309
• LogP: 0.20940
• Storage Temp.: -20°C Freezer
• Solubility.: DMSO (Slightly), Methanol (Slightly, Heated)
• 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:

99.9% ^*data from raw suppliers

Nebivolol ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Canonical SMILES: C1CC2=C(C=CC(=C2)F)OC1C(CNCC(C3CCC4=C(O3)C=CC(=C4)F)O)O
• Isomeric SMILES: C1CC2=C(C=CC(=C2)F)O[C@H]1[C@H](CNC[C@@H]([C@@H]3CCC4=C(O3)C=CC(=C4)F)O)O
• Recent EU Clinical Trials: Effects of nebivolol on the cardiovascular functions, thermoregulation and blood flow during real and simulated conditions of microgravity
• Uses: Antihypertensive (β-blocker). Nebivolol is a cardioselective beta-1 receptor blocking agent.
• Clinical Use: Beta-adrenoceptor blocker: Essential hypertension Adjunct in heart failure
• Drug interactions: Potentially hazardous interactions with other drugs Anaesthetics: enhanced hypotensive effect. Analgesics: NSAIDs antagonise hypotensive effect. Anti-arrhythmics: increased risk of myocardial depression and bradycardia; increased risk of bradycardia, myocardial depression and AV block with amiodarone; increased risk of myocardial depression and bradycardia with flecainide. Antidepressants: enhanced hypotensive effect with MAOIs. Antihypertensives; enhanced hypotensive effect; increased risk of withdrawal hypertension with clonidine; increased risk of first dose hypotensive effect with post-synaptic alpha-blockers such as prazosin. Antimalarials: increased risk of bradycardia with mefloquine. Antipsychotics enhanced hypotensive effect with phenothiazines. Calcium-channel blockers: increased risk of bradycardia and AV block with diltiazem; hypotension and heart failure possible with nifedipine and nisoldipine; asystole, severe hypotension and heart failure with verapamil. Cytotoxics: possible increased risk of bradycardia with crizotinib. Diuretics: enhanced hypotensive effect. Fingolimod: possibly increased risk of bradycardia. Moxisylyte: possible severe postural hypotension. Sympathomimetics: severe hypertension with adrenaline and noradrenaline and possibly with dobutamine.

Technology Process of Levonebivolol

There total 64 articles about Levonebivolol 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: 67.0%

l-(R,S,S,S)-benzyl nebivolol hydrochloride (1224567-85-4) → nebivolol (118457-16-2,118457-14-0,118457-15-1,119365-25-2,119365-23-0,1360598-84-0)

Guidance literature:

l-(R,S,S,S)-benzyl nebivolol hydrochloride; With sodium hydroxide; In water; iso-butanol; at 25 ℃; Inert atmosphere;

With formic acid; 5% Pd(II)/C(eggshell); In iso-butanol; at 70 ℃; for 4h;

With sodium hydroxide; In water; iso-butanol;

Reference yield: 62.0%

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 (682359-63-3) → nebivolol (118457-16-2,118457-14-0,118457-15-1,119365-25-2,119365-23-0,1360598-84-0)

Guidance literature:

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; With hydrogenchloride; hydrogen; palladium 10% on activated carbon; In ethanol; water; at 50 - 55 ℃; for 16h; under 2250.23 Torr;

With sodium hydrogencarbonate; In water; pH=8;

Reference yield: 48.0%

(2S)-6-fluoro-2-[(2S)-oxiran-2-yl]-3,4-dihydro-2H-chromene (129050-23-3,793669-26-8,876514-31-7) + 2-amino-1-[6-fluoro-(2R)-3,4-dihydro-2H-2-benzopyran]-(1S)-1-ethanol hydrochloride → nebivolol (118457-16-2,118457-14-0,118457-15-1,119365-25-2,119365-23-0,1360598-84-0)

Guidance literature:

With boron trifluoride diethyl etherate; In isopropyl alcohol; Reflux;

upstream raw materials:

nebivolol

(R)-2-amino-1-[(S)-6-fluoro-3,4-dihydro-2H-chromen-2-yl]ethanol

(R)-2-[(R)-6-fluoro-3,4-dihydro-2H-chromen-2-yl]-2-hydroxyethyl-4-methylbenzenesulfonate

(S)-2-[(R)-2,2-dimethyl-1,3-dioxolan-4-yl]-6-fluoro-2,3-dihydrochromen-4-one

Downstream raw materials:

DL-nebivolol hydrochloride

nebivolol hydrochloride

nebivolol hydrochloride

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

Refernces

• 1、 Wang, Nai-Xing,Yu, An-Guang,Wang, Gui-Xia,Zhang, Xiu-Hui,Li, Qian-Shu,Li, Zhen. "Synthesis of (S,R,R,R)-α,α′-iminobis(methylene)bis(6- fluoro-3H,4H-dihydro-2H-1-benzopyran-2-methanol)". . p. 1154 - 1158. Retrieved 2007.
• 2、 -. "Preparation method and application of Smo inhibitor based on Nebivolol". . . Retrieved 2019/10/17.
• 3、 -. "A NEW METHOD FOR PRODUCING NEBIVOLOL HYDROCHLORIDE OF HIGH PURITY". Page/Page column 22. . Retrieved 2015/09/22.