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네비보롤

Nebivolol

HCID 71301
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기본 정보개요이름 및 식별자물성안전 및 규제화학 및 산업관련 반응화합물 노트
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기본 정보

CAS
118457-14-0
표준 SMILES
OC(CNCC(O)C1CCc2cc(F)ccc2O1)C1CCc2cc(F)ccc2O1
InChIKey
KOHIRBRYDXPAMZ-UHFFFAOYSA-N
분자식
C22H25F2NO4
평균 분자량
405.4 g/mol
단동위원소 질량
405.1751646

개요

2,2'-iminobis[1-(6-fluoro-3,4-dihydro-2H-chromen-2-yl)ethanol] is a member of the class of chromanes that is 2,2'-iminodiethanol in which one hydrogen attached to each hydroxy-bearing carbon is replaced by a 6-fluorochroman-2-yl group. It is a member of chromanes, a diol, a secondary alcohol, an organofluorine compound and a secondary amino compound.

이름 및 식별자

우선 이름
Nebivolol
IUPAC
1-(6-fluoro-3,4-dihydro-2H-chromen-2-yl)-2-[[2-(6-fluoro-3,4-dihydro-2H-chromen-2-yl)-2-hydroxyethyl]amino]ethanol
현지명
네비보롤
영어명
Nebivolol
분자식
C22H25F2NO4
분자량
405.43

이름 및 동의어

NebivololNarbivolol118457-14-0R-65824dl-NebivololDTXSID9040556R65,8241-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)-2-{[2-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)-2-hydroxyethyl]amino}ethan-1-olNebivololumnebibololHypoloc1-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)-2-((2-(6-fluoro-3,4-dihydro-2H-1-benzopyran-2-yl)-2-hydroxyethyl)amino)ethan-1-ol
이름 더 보기
네비보롤NibivololNebivilolNEBIVOLOL-D4NEBIVOLOL-D6(Rac)-NebivololNebilolol impurity 11Nebivolol (10mM in DMSO)rac-Nebivolol (Mixture of Diastereomers)2,2'-Azanediylbis(1-(6-fluorochroman-2-yl)ethanol)
Hydrochloride, NebivololRefChem:56585alpha,alpha'-(iminobis(methylene))bis(6-fluoro-3,4-dihydro)-2H-1-benzopyran-2-methanolDTXCID7020556CHEBI:64022C07AB12R6755567555, R

물성

구조 계산 물성

XLogP
3
극성 표면적
71 Ų
수소 결합 공여자 수
3
수소 결합 수용자 수
7
회전 가능 결합 수
6
무거운 원자 수
29
형식 전하
0
복잡도
483

실험 및 물리화학적 성질

Drugs · 4건

Pharmaceuticals -> Cardiovascular system -> Beta blocking agents

Pharmaceuticals -> Used in Switzerland

Pharmaceuticals

Pharmaceuticals -> Antihypertensives

LogP2.76
Solubility · 2건

0.091g/100mL

4.03e-02 g/L

Human Drugs · 2건

Breast Feeding; Lactation; Milk, Human; Adrenergic beta-Antagonists; Antihypertensive Agents; Vasodilator Agents

Pharmaceuticals

Melting Point223.0-228.0
Physical DescriptionSolid
Dissociation Constants · 2건

8.22

8.13

물리화학적 성질

끓는 점
600.5 · 600.5±55.0 °C(Predicted)
밀도
1.309 · 1.309±0.06 g/cm3(Predicted)
저장 조건
2 · 2-8°C(protect from light)
용해도

안전 및 규제

안전 정보는 참고용이며, 공급업체의 물질안전보건자료(SDS), 관련 법규 및 전문가 평가를 대체하지 않습니다.

GHS 분류

GHS Classification · 4건

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P203, P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P317, P318, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 2 reports by companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

유해성 정보

Regulatory InformationREACH registered substance: 2H-1-Benzopyran-2-methanol, a,a'-[iminobis(methylene)]bis[6-fluoro-3,4-dihydro-, (aR,a'R,2R,2'S)-rel- (EC: 601-527-4)
Hazard Classes and CategoriesAcute Tox. 4 (100%)

독성 정보

Hepatotoxicity · 1건

Mild-to-moderate elevations in serum aminotransferase levels occur in less than 2% of patients on beta-blockers and are usually transient and asymptomatic, resolving even with continuation of therapy. There is no information on the rates of ALT elevations during nebivolol therapy. Despite its use in several large clinical trials, nebivolol has not been linked to cases of clinically apparent liver injury.

Adverse EffectsNebivolol's reported adverse effects typically involve the central nervous system (CNS). Headache is the most commonly reported adverse effect (6% to 9%).
Toxicity SummarySigns and Symptoms of Overdose
Drug Induced Liver Injury · 5건

Drug-Induced Liver Injury Severity and Toxicity (DILIst)

화학 및 산업

약리 정보

ATC Code · 3건

C07AB12

C - Cardiovascular system

QC - Cardiovascular system

Protein BindingNebivolol is 98% bound to plasma proteins, mostly to serum albumin.
Pharmacodynamics · 1건

Nebivolol is a selective beta-1 adrenergic receptor antagonist that decreases vascular resistance, increases stroke volume and cardiac output, and does not negatively affect left ventricular function. It has a long duration of action as effects can be seen 48 hours after stopping the medication and a wide therapeutic window as patients generally take 5-40mg daily. Patients should not abruptly stop taking this medication as this may lead to exacerbation of coronary artery disease. Diabetic patients should monitor their blood glucose levels as beta blockers may mask signs of hypoglycemia.

Mechanism of Action · 1건

Nebivolol is a highly selective beta-1 adrenergic receptor antagonist with weak beta-2 adrenergic receptor antagonist activity. Blocking beta-1 adrenergic receptors by d-nebivolol leads to decreased resting heart rate, exercise heart rate, myocardial contracility, systolic blood pressure, and diastolic blood pressure. The selectivity of d-nebivolol limits the magnitude of beta blocker adverse effects in the airways or relating to insulin sensitivity. Nebivolol also inhibits aldosterone, and beta-1 antagonism in the juxtaglomerular apparatus also inhibits the release of renin. Decreased aldosterone leads to decreased blood volume, and decreased renin leads to reduced vasoconstriction. l-nebivolol is responsible for beta-3 adrenergic receptor agonist activity that stimulates endothelial nitric oxide synthase, increasing nitric oxide levels; leading to vasodilation, decreased peripheral vascular resistance, increased stroke volume, ejection fraction, and cardiac output. The vasodilation, reduced oxidative stress, and reduced platelet volume and aggregation of nebivolol may lead to benefits in heart failure patients.

Biological Half-Lifed-nebivolol has a half life of 12 hours in CYP2D6 extensive metabolizers and 19 hours in poor metabolizers.
Metabolism/Metabolites · 1건

관련 반응

7건
반응 기록 만들기
HRID 451585 반응식
HRID 451585반응물로uspto-grants-2013_07
HRID 473062 반응식
HRID 473062반응물로uspto-grants-2014_01
HRID 962365 반응식
HRID 962365반응물로uspto-grants-1998_06
HRID 1627755 반응식
HRID 1627755반응물로uspto-grants-2014_07
HRID 1911955 반응식
HRID 1911955반응물로uspto-grants-2013_12
HRID 2267199 반응식
HRID 2267199생성물로uspto-grants-2010_12
HRID 2267200 반응식
HRID 2267200반응물로uspto-grants-2010_12

화합물 노트

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데이터베이스 식별자

CAS
118457-14-0、99200-09-6
PubChem CID
71301
DTXSID
DTXSID9040556
ChEMBL
CHEMBL434394
ChEBI
CHEBI:64019
EC Number
601-527-4、881-355-6
Nikkaji
J33.390E
DMSO(약간 용해됨), 메탄올(약간 용해됨, 가열)
물리적 상태
고체
산도 계수 (pKa)
14.29 · 14.29±0.20(Predicted)
색상
흰색에서 황백색까지
InChIKey
KOHIRBRYDXPAMZ-AWIIVWKDNA-N
SMILES
C([2H])([2H])([C@H](O)[C@@]1([H])CCC2C=C(C=CC=2O1)F)NC([2H])([2H])[C@H](O)[C@]1([H])CCC2C=C(C=CC=2O1)F |&1:3,5,21,23,r|

nebivolol

DILI Negative

Oral

DOI:10.1016/j.drudis.2019.09.022

Effects During Pregnancy and Lactation◉ Summary of Use during Lactation
EPA Human Health Benchmarks for Pharmaceuticals · 6건

Nebivolol

0.1

0.5

For most patients, the recommended starting dose is 5 mg once daily. For patients requiring further reduction in blood pressure, the dose can be increased at 2-week intervals up to 40 mg.

Data used to generate the benchmarks include the following: Lowest Daily Dose (LDD): 5 mg/day, Lowest Therapeutic Dose (LTD): 0.1 mg/kg-day, and Screening Dose: 0.00002 mg/kg-day.

16-Dec-21

Nebivolol is metabolized mainly by glucuronidation and CYP2D6 mediated hydroxylation. Metabolism involves n-dealkylation, hydroxylation, oxidation, and glucuronidation. Aromatic hydroxyl and acyclic oxide metabolites are active, while n-dealkylated and glucuronides are inactive.

FDA Pharmacological Classification · 6건

030Y90569U

NEBIVOLOL

Mechanisms of Action [MoA] - Adrenergic beta-Antagonists

Established Pharmacologic Class [EPC] - beta-Adrenergic Blocker

Nebivolol is a beta-Adrenergic Blocker. The mechanism of action of nebivolol is as an Adrenergic beta-Antagonist.

NEBIBOLOL

MeSH Pharmacological Classification · 3건

Drugs used in the treatment of acute or chronic vascular HYPERTENSION regardless of pharmacological mechanism. Among the antihypertensive agents are DIURETICS; (especially DIURETICS, THIAZIDE); ADRENERGIC BETA-ANTAGONISTS; ADRENERGIC ALPHA-ANTAGONISTS; ANGIOTENSIN-CONVERTING ENZYME INHIBITORS; CALCIUM CHANNEL BLOCKERS; GANGLIONIC BLOCKERS; and VASODILATOR AGENTS.

Drugs used to cause dilation of the blood vessels.

Compounds that bind to and activate ADRENERGIC BETA-1 RECEPTORS.

Absorption, Distribution and Excretion · 4건

The absorption of nebivolol is not affected by food. Nebivolol has a Tmax of 1.5-4 hours. Bioavailability can range from 12-96% for extensive to poor CYP2D6 metabolizers. For a 20mg dose, d-nebivolol has a Cmax of 2.75±1.55ng/mL, l-nebivolol has a Cmax of 5.29±2.06ng/mL, both enantiomers have a Cmax of 8.02±3.47ng/mL, and nebivolol glucuronides have a Cmax of 68.34±44.68ng/mL. For a 20mg dose, d-nebivolol has an AUC of 13.78±15.27ng\*h/mL, l-nebivolol has an AUC of 27.72±15.32ng\*h/mL, both enantiomers have an AUC of 41.50±29.76ng\*h/mL, and nebivolol glucuronides have an AUC of 396.78±297.94ng\*h/mL.

In extensive CYP2D6 metabolizers, 38% is eliminated in the urine and 44% in the feces. In poor CYP2D6 metabolizers, 67% is eliminated in the urine and 13% in the feces. <1% of a dose is excreted as the unmetabolized drug.

For a 20mg dose, d-nebivolol has an apparent volume of distribution of 10,290.81±3911.72L, l-nebivolol has an apparent volume of distribution of 8,066.66±4,055.50L, and both enantiomers together have a volume of distribution of 10,423.42±6796.50L.

For a 20mg dose, the clearance of d-nebivolol is 1241.63±749.77L/h, l-nebivolol is 435.53±180.93L/h, and both enantiomers is 635.31±300.25L/h.

Cellular LocationsMembrane
Metabolite PathwaysNebivolol Action Pathway

용도 및 제조

UsesUse (kg; approx.) in Germany (2009): >750
Use ClassificationPharmaceuticals
응용 분야 · 2건

개요Nebilet 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.

용도Labeled Nebivolol, intended for use as an internal standard for the quantification of Nebivolol by GC- or LC-mass spectrometry.

상·하류 제품 정보

하류 제품

네비볼롤

추가 설명

정의ChEBI: A member of the class of chromanes that is 2,2'-iminodiethanol in which one hydrogen attached to each hydroxy-bearing carbon is replaced by a 6-fluorochroman-2-yl group.