(-)-Nebivolol - CAS 118457-16-2
Not Intended for Therapeutic Use. For research use only.
Category:
Inhibitor
Product Name:
(-)-Nebivolol
Catalog Number:
118457-16-2
Synonyms:
(αS,α’S,2R,2’S)-α,α’-[Iminobis(methylene)]bis[6-fluoro-3,4-dihydro-2H-1-benzopyran-2-methanol]; [2S-[2R*[R*[R*(S*)]]]]-α,α’-[Iminobis(methylene)]bis[6-fluoro-3,4-dihydro- 2H-1-benzopyran-2-methanol; Levonebivolol; R 67145; l-Nebivolol
CAS Number:
118457-16-2
Description:
This active molecular is a β-adrenergic receptor antagonist. Levonebivolol is an enantiomer of Nebivolol which is a β1 receptor blocker with nitric oxide-potentiating vasodilatory effect used in treatment of hypertension and left ventricular failure in Europe. It is highly cardioselective under certain circumstances. In Apr 2015, US FDA approved an ANDA for nebivolol submitted by Amerigen. In Jan 2016, Forest Laboratories and the University of Chicago withdrew a phase II/III trial for Hypertension in patients with chronic obstructive pulmonary disease in USA .
Molecular Weight:
405.44
Molecular Formula:
C22H25F2NO4
Quantity:
Milligrams-Grams
Quality Standard:
In-house standard
COA:
Inquire
MSDS:
Inquire
Canonical SMILES:
C1CC2=C(C=CC(=C2)F)OC1C(CNCC(C3CCC4=C(O3)C=CC(=C4)F)O)O
InChI:
InChI=1S/C22H25F2NO4/c23-15-3-7-19-13(9-15)1-5-21(28-19)17(26)11-25-12-18(27)22-6-2-14-10-16(24)4-8-20(14)29-22/h3-4,7-10,17-18,21-22,25-27H,1-2,5-6,11-12H2/t17-,18-,21-,22-/m0/s1
InChIKey:
KOHIRBRYDXPAMZ-GPHNJDIKSA-N
Targets:
Adrenergic Receptor
Current Developer:
Duncan; Forest Laboratories; Janssen; Menarini
Chemical Structure
CAS 118457-16-2 (-)-Nebivolol

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Reference Reading


1.Development and validation of a stability-indicating reverse phase ultra performance liquid chromatographic method for the estimation of nebivolol impurities in active pharmaceutical ingredients and pharmaceutical formulation.
Thummala VR, Lanka MK. Se Pu. 2015 Oct;33(10):1051-8.
A sensitive, stability-indicating gradient reverse phase ultra performance liquid chromatographic method has been developed for the quantitative estimation of nebivolol impurities in active pharmaceutical ingredient (API) and pharmaceutical formulation. Efficient chromatographic separation was achieved on an Acquity BEH C18 column (100 mm x 2.1 mm, 1.7 μm) with mobile phase of a gradient mixture. The flow rate of the mobile phase was 0.18 mL/min with column temperature of 30 degrees C and detection wavelength of 281 nm. The relative response factor values of (R*)-2-( benzylamino)-1-((S*)-6-fluorochroman-2-yl) ethanol ((R x S*) NBV-), (R)-1-((R)-6-fluorochroman-2-yl)-2-((S)-2-((S)-6-fluoro-chroman-2-yl)-2-hydroxyethyl-amino) ethanol ((RRSS) NBV-3), 1-(chroman-2-yl)-2-(2-(6-fluorochroman-2-yl)-2-hydroxyethyl amino) ethanol (monodesfluoro impurity), (S)-1-((R)-6-fluorochroman-2-yl)-2-((R)-2 (S*)-6-fluoro-chroman-2-yl)-2-hydroxyethylamino) ethanol hydrochloride ((RSRS) NBV-3) and (R*)-1-((S*)-6-fluorochroman-2-yl)-2-((S*)-2-((S*)-6-fluoro-chroman-2-yl)-2-hydroxyethylamino) ethanol ((R* S* S* S*) NBV-2) were 0.
2.Chronic Nebivolol Treatment Suppresses Endothelin-1-Mediated Vasoconstrictor Tone in Adults With Elevated Blood Pressure.
Diehl KJ1, Stauffer BL1, Dow CA1, Bammert TD1, Brunjes DL1, Greiner JJ1, DeSouza CA2. Hypertension. 2016 Apr 25. pii: HYPERTENSIONAHA.115.06979. [Epub ahead of print]
Endothelin-1 (ET-1) plays a major role in the pathophysiology of hypertension and its associated cardiovascular risk. We tested the hypothesis that chronic nebivolol treatment reduces ET-1-mediated vasoconstrictor tone in adult humans with elevated blood pressure (BP). Furthermore, reducing ET-1 vasoconstrictor activity contributes to the improvement in endothelial vasodilator function associated with nebivolol treatment. Forty-two middle-aged adults with elevated BP (systolic BP ≥130 mm Hg or diastolic BP ≥85 mm Hg) completed a 3-month, double-blind, randomized, placebo controlled trial: 14 received nebivolol (8 men/6 women; 5 mg per day); 14 received metoprolol succinate (9 men/5 women; 100 mg per day); and 14 received placebo (9 men/5 women). Forearm blood flow (plethysmography) responses to selective (BQ-123: 100 nmol/min; 60 minutes) and nonselective (BQ-123+BQ-788 [50 nmol/min]; 60 minutes) ET-1 receptor blockade, as well as acetylcholine (4.
3.Nebivolol, a β1-adrenergic blocker, protects from peritoneal membrane damage induced during peritoneal dialysis.
Liappas G1, González-Mateo G1, Aguirre AR2, Abensur H2, Albar-Vizcaino P3, González Parra E4, Sandoval P1, García Ramírez L3, Del Peso G5, Acedo JM6, Bajo MA5, Selgas R5, Sánchez Tomero JA3, López-Cabrera M1, Aguilera A3. Oncotarget. 2016 Apr 18. doi: 10.18632/oncotarget.8780. [Epub ahead of print]
Peritoneal dialysis (PD) is a form of renal replacement treatment, which employs the peritoneal membrane (PM) to eliminate toxins that cannot be removed by the kidney. The procedure itself, however, contributes to the loss of the PM ultrafiltration capacity (UFC), leading consequently to the technique malfunction. β-blockers have been considered deleterious for PM due to their association with loss of UFC and induction of fibrosis. Herein we analyzed the effects of Nebivolol, a new generation of β1-blocker, on PM alterations induced by PD fluids (PDF). In vitro: We found that mesothelial cells (MCs) express β1-adrenergic receptor. MCs were treated with TGF-β to induce mesothelial-to-mesenchymal transition (MMT) and co-treated with Nebivolol. Nebivolol reversed the TGF-β effects, decreasing extracellular matrix synthesis, and improved the fibrinolytic capacity, decreasing plasminogen activator inhibitor-1 (PAI-1) and increasing tissue-type plasminogen activator (tPA) supernatant levels.
4.Fixed-dose combination therapy of nebivolol and valsartan for the treatment of hypertension.
Sander GE1, Fernandez C1, Giles TD1. Expert Rev Cardiovasc Ther. 2016 May;14(5):563-72. doi: 10.1586/14779072.2016.1167598. Epub 2016 Apr 7.
Recent large clinical trials have refuted earlier suggestions from the Joint National Committee 8 committee that less aggressive targets for blood pressure control were all that could be justified in most hypertensive patients. It now does appear that in fact "lower is better," with blood pressure targets < 120/80 mm Hg appropriate for many hypertensive patients. Two drug combinations are often indicated as initial therapy if a 20/10 mm Hg or greater blood pressure reduction is necessary to reach target. Combinations consisting of β-blockers and renin-angiotensin-aldosterone system inhibitors have previously been deemed "less effective," based on partially overlapping mechanisms of action and limited clinical trial evidence. Nebivolol is a vasodilating β1-selective blocker and β3- adrenoceptor agonist; β3-adrenoceptor activation increases nitric oxide concentrations and thus explains the vasodilatory effect. A recent 8-week randomized trial (N=4,161) in individuals with stage 1-2 hypertension demonstrated that single-pill fixed dose combinations (FDC) of nebivolol and valsartan, an angiotensin II subtype 1 receptor blocker, were more effective in reducing blood pressure than the corresponding monotherapies, with comparable tolerability.