CAS 72956-09-3|1-((9H-carbazol-4-yl)oxy)-3-((2-(2-methoxyphenoxy)ethyl)amino)propan-2-ol|[3-(9H-carbazol-4-yloxy)-2-hydroxypropyl][2-(2-methoxyphenoxy)ethyl]amine|carvedilol|carvedilol|Carvedilol|Co...

General Information

Structure

Molecular Formula

C₂₄H₂₆N₂O₄

Molecular Mass

406.47424

Exact Mass

406.18925732

Charge

InChI

InChI=1S/C24H26N2O4/c1-28-21-10-4-5-11-22(21)29-14-13-25-15-17(27)16-30-23-12-6-9-20-24(23)18-7-2-3-8-19(18)26-20/h2-12,17,25-27H,13-16H2,1H3

InChIKey

OGHNVEJMJSYVRP-UHFFFAOYSA-N

Canonic Smiles

COc1ccccc1OCCNCC(COc1cccc2c1c1ccccc1[nH]2)O

Isomeric Smiles

O(c1c2c3c([nH]c2ccc1)cccc3)CC(O)CNCCOc1c(OC)cccc1

Calculated Properties

JChem

LogD (pH = 7.4)

2.07

LogD (pH = 5.5)

0.48

Log P

3.42

Rotatable Bonds

H Donor

H Acceptors

Lipinski's Rule of Five

true

Acid pKa

8.74

Polar Surface Area

75.74

Polarizability

45.35

Molar Refractivity

115.64

LOG S

-5.65

Data Source

Names and Identifiers

Synonyms

1-((9H-carbazol-4-yl)oxy)-3-((2-(2-methoxyphenoxy)ethyl)amino)propan-2-olcarvedilolCarvedilolCarvedilolum [Latin]CoregDilatrend1-(9H-Carbazol-4-yloxy)-3-[[2-(2-methoxyphenoxy)ethyl]amino]-2-propanolCarvedilolBM-14190CarvasKorvasanCarcaCarvediolKredexArtistCarlocSKF 105517TallitonDimitoneCadilanEucardicCardivasQuertoBM 14190DQ 2466SKF 105517carvedilol(+-)-1-(Carbazol-4-yloxy)-3-((2-(o-methoxyphenoxy)ethyl)amino)-2-propanolCarvedilol

IUPAC name

[3-(9H-carbazol-4-yloxy)-2-hydroxypropyl][2-(2-methoxyphenoxy)ethyl]amine 1-(9H-carbazol-4-yloxy)-3-{[2-(2-methoxyphenoxy)ethyl]amino}propan-2-ol

IUPAC Traditional name

carvedilol [3-(9H-carbazol-4-yloxy)-2-hydroxypropyl][2-(2-methoxyphenoxy)ethyl]amine

Brand Name

Coreg CRCoreg

API Name

Carvedilol

International Nonproprietary Name (INN)

carvedilolcarvedilolum

Names and Identifiers

Registration numbers

Properties

Product Information

Purity

>98%

≥98% (HPLC)

Salt Data

Free Base

Empirical Formula (Hill Notation)

C24H26N2O4

Certificate of Analysis

Download link

Application(s)

Vasodilator

Pharmacology Properties

Target

adrenergic receptor

Mechanism of Action

Calcium channel blocker

Beta-Adrenoceptor blocker

Properties

Related Proteins

No Data Available

Click here to submit data

Molecular Spectra

No Data Available

Click here to submit data

Molecule Details

Selleck Chemicals

S1831

Biological Activity:
Carvedilol is a non-selective beta blocker/alpha-1 blocker with an IC50 of 3.8 μM for inhibition of LDL oxidation. [1] Norepinephrine stimulates the nerves that control the muscles of the heart by binding to the β1- and β2-adrenergic receptors. Carvedilol blocks the binding to those receptors, which both slows the heart rhythm and reduces the force of the heart’s pumping. This lowers blood pressure and reduces heart failure. Norepinephrine also binds to the α1-adrenergic receptors on blood vessels, causing them to constrict and raise blood pressure. Carvedilol blocks this binding to the α1-adrenergic receptors too, which also lowers blood pressure. [2]

DrugBank

DB01136

Drug Groups

approved; investigational

Description

Carvedilol is a non-selective beta blocker indicated in the treatment of mild to moderate congestive heart failure (CHF). It blocks beta-1 and beta-2 adrenergic receptors as well as the alpha-1 adrenergic receptors.

Indication

For the treatment of mild or moderate (NYHA class II or III) heart failure of ischemic or cardiomyopathic origin.

Pharmacology

Carvedilol is a nonselective beta-adrenergic blocking agent with alpha1-blocking activity and is indicated for the treatment of hypertension and mild or moderate (NYHA class II or III) heart failure of ischemic or cardiomyopathic origin. Carvedilol is a racemic mixture in which nonselective b-adrenoreceptor blocking activity is present in the S(-) enantiomer and a-adrenergic blocking activity is present in both R(+) and S(-) enantiomers at equal potency. Carvedilol has no intrinsic sympathomimetic activity. The effect of carvedilol's b-adrenoreceptor blocking activity has been demonstrated in animal and human studies showing that carvedilol (1) reduces cardiac output in normal subjects; (2) reduces exercise-and/or isoproterenol-induced tachycardia and (3) reduces reflex orthostatic tachycardia.

Toxicity

Not expected to be toxic following ingestion.

Affected Organisms

Humans and other mammals

Biotransformation

Hepatic. Carvedilol is metabolized primarily by aromatic ring oxidation and glucuronidation. The oxidative metabolites are further metabolized by conjugation via glucuronidation and sulfation. Demethylation and hydroxylation at the phenol ring produce three active metabolites with b-receptor blocking activity. The 4'-hydroxyphenyl metabolite is approximately 13 times more potent than carvedilol for b-blockade.

Absorption

Carvedilol is rapidly and extensively absorbed following oral administration, with an absolute bioavailability of approximately 25% to 35% due to a significant degree of first-pass metabolism.

Half Life

7-10 hours

Protein Binding

98%

Elimination

Carvedilol is extensively metabolized. Less than 2% of the dose was excreted unchanged in the urine.
Carvedilol is metabolized primarily by aromatic ring oxidation and glucuronidation. The oxidative metabolites are further metabolized by conjugation via glucuronidation and sulfation. The metabolites of carvedilol are excreted primarily via the bile into the feces.

Distribution

* 115 L

Clearance

* 500-700 mL/min

References

• Packer M, Fowler MB, Roecker EB, Coats AJ, Katus HA, Krum H, Mohacsi P, Rouleau JL, Tendera M, Staiger C, Holcslaw TL, Amann-Zalan I, DeMets DL: Effect of carvedilol on the morbidity of patients with severe chronic heart failure: results of the carvedilol prospective randomized cumulative survival (COPERNICUS) study. Circulation. 2002 Oct 22;106(17):2194-9. [Pubmed]

• Packer M, Coats AJ, Fowler MB, Katus HA, Krum H, Mohacsi P, Rouleau JL, Tendera M, Castaigne A, Roecker EB, Schultz MK, DeMets DL: Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001 May 31;344(22):1651-8. [Pubmed]

• Vanderhoff BT, Ruppel HM, Amsterdam PB: Carvedilol: the new role of beta blockers in congestive heart failure. Am Fam Physician. 1998 Nov 1;58(7):1627-34, 1641-2. [Pubmed]

External Links

• [Wikipedia]

• [RxList]

• [Drugs.com]

Sigma Aldrich

C3993

Biochem/physiol Actions
Cavedilol is a non-selective β-adrenergic blocker with α1 blocking activity. Carvedilol is used specifically for the treatment of heart failure and high blood pressure. It has been shown to improve left ventricular ejection fraction and may reduce mortality.
Other Notes
Tandem Mass Spectrometry data independently generated by Scripps Center for Metabolomics is available to view or download in PDF. C3993.pdf Tested metabolites are featured on Scripps Center for Metabolomics METLIN Metabolite Database. To learn more, visit sigma.com/metlin.

TRC

C184625

Carvedilol is a nonselective β-adrenergic blocker with α1-blocking activity. Carvedilol is an antihypertensive used in the treatment of congestive heart failure.

ChEBI

CHEBI:3441

A member of the class of carbazoles that is an adrenergic antagonist with non-selective beta- and alpha-1 receptor blocking properties which helps in the management of congestive heart failure.

Molecule Details

References

PubChem Literature

From Data Sources

• Vanderhoff BT, Ruppel HM, Amsterdam PB: Carvedilol: the new role of beta blockers in congestive heart failure. Am Fam Physician. 1998 Nov 1;58(7):1627-34, 1641-2. Pubmed

• http://en.wikipedia.org/wiki/Carvedilol

• Hirohashi, M., et al.: Arzneim.-Forsch., 40, 735 (1990)

• Packer, M., et al.: N. Engl. J. Med., 334, 1349 (1990)

• Martindale, The Extra Pharmacopoeia, 30th edn., Pharmaceutical Press, 1993, 632

• Rabasseda, X. et al., Drugs of Today (Barcelona), 1998, 34, 905-926

• Beta-blockers in Clinical Practice, (Eds. Cruickshank, J.M. et al), 2nd edn., Churchill Livingstone, 1994, 1119, (book)

• Cubeddu, L.X. et al., Clin. Pharmacol. Ther. (St. Louis), 1987, 41, 31, (pharmacol)

• Ruffolo, R.R. et al., Cardiovasc. Drug Rev., 1992, 10, 127, (rev)

• Sponer, G. et al., J. Cardiovasc. Pharmacol., (Suppl. 11), 1987, 10, S49, (pharmacol)

• Dunn, C.J., Drugs, 1997, 53, 161-185, (rev)

• Wood, A.J.J. et al., N. Engl. J. Med., 1998, 339, 1759-1765, (rev)

• Abshagen, U., J. Cardiovasc. Pharmacol., (Suppl. 11), 1987, 10, S23, (rev, pharmacol)

• Reiff, K., J. Chromatogr., 1987, 413, 355, (hplc)

• McTavish, D. et al., Drugs, 1993, 45, 232, (rev)

• Ger. Pat., 1984, 3 319 027; CA, 102, 113292, (resoln)

• Ger. Pat., 1984, 2 815 926; CA, 92, 128716e, (synth)

• Neugebauer, G. et al., Eur. J. Clin. Pharmacol., 1990, 38, S108, (pharmacol, isomers)

References

Bioactivity

PubChem BioAssay

Bioactivity

Names and Identifiers

Synonyms

IUPAC name

[3-(9H-carbazol-4-yloxy)-2-hydroxypropyl][2-(2-methoxyphenoxy)ethyl]amine 1-(9H-carbazol-4-yloxy)-3-{[2-(2-methoxyphenoxy)ethyl]amino}propan-2-ol

IUPAC Traditional name

carvedilol [3-(9H-carbazol-4-yloxy)-2-hydroxypropyl][2-(2-methoxyphenoxy)ethyl]amine

Brand Name

Coreg CRCoreg

API Name

Carvedilol

International Nonproprietary Name (INN)

carvedilolcarvedilolum

Molecule Details

Selleck Chemicals

S1831

DrugBank

DB01136

Drug Groups

approved; investigational

Description

Indication

For the treatment of mild or moderate (NYHA class II or III) heart failure of ischemic or cardiomyopathic origin.

Pharmacology

Toxicity

Not expected to be toxic following ingestion.

Affected Organisms

Humans and other mammals

Biotransformation

Absorption

Carvedilol is rapidly and extensively absorbed following oral administration, with an absolute bioavailability of approximately 25% to 35% due to a significant degree of first-pass metabolism.

Half Life

7-10 hours

Protein Binding

98%

Elimination

Distribution

* 115 L

Clearance

* 500-700 mL/min

References

• Vanderhoff BT, Ruppel HM, Amsterdam PB: Carvedilol: the new role of beta blockers in congestive heart failure. Am Fam Physician. 1998 Nov 1;58(7):1627-34, 1641-2. [Pubmed]

External Links

• [Wikipedia]

• [RxList]

• [Drugs.com]

Sigma Aldrich

C3993

TRC

C184625

Carvedilol is a nonselective β-adrenergic blocker with α1-blocking activity. Carvedilol is an antihypertensive used in the treatment of congestive heart failure.

ChEBI

CHEBI:3441

A member of the class of carbazoles that is an adrenergic antagonist with non-selective beta- and alpha-1 receptor blocking properties which helps in the management of congestive heart failure.

References

PubChem Literature

From Data Sources

• Vanderhoff BT, Ruppel HM, Amsterdam PB: Carvedilol: the new role of beta blockers in congestive heart failure. Am Fam Physician. 1998 Nov 1;58(7):1627-34, 1641-2. Pubmed

• http://en.wikipedia.org/wiki/Carvedilol

• Hirohashi, M., et al.: Arzneim.-Forsch., 40, 735 (1990)

• Packer, M., et al.: N. Engl. J. Med., 334, 1349 (1990)

• Martindale, The Extra Pharmacopoeia, 30th edn., Pharmaceutical Press, 1993, 632

• Rabasseda, X. et al., Drugs of Today (Barcelona), 1998, 34, 905-926

• Beta-blockers in Clinical Practice, (Eds. Cruickshank, J.M. et al), 2nd edn., Churchill Livingstone, 1994, 1119, (book)

• Cubeddu, L.X. et al., Clin. Pharmacol. Ther. (St. Louis), 1987, 41, 31, (pharmacol)

• Ruffolo, R.R. et al., Cardiovasc. Drug Rev., 1992, 10, 127, (rev)

• Sponer, G. et al., J. Cardiovasc. Pharmacol., (Suppl. 11), 1987, 10, S49, (pharmacol)

• Dunn, C.J., Drugs, 1997, 53, 161-185, (rev)

• Wood, A.J.J. et al., N. Engl. J. Med., 1998, 339, 1759-1765, (rev)

• Abshagen, U., J. Cardiovasc. Pharmacol., (Suppl. 11), 1987, 10, S23, (rev, pharmacol)

• Reiff, K., J. Chromatogr., 1987, 413, 355, (hplc)

• McTavish, D. et al., Drugs, 1993, 45, 232, (rev)

• Ger. Pat., 1984, 3 319 027; CA, 102, 113292, (resoln)

• Ger. Pat., 1984, 2 815 926; CA, 92, 128716e, (synth)

• Neugebauer, G. et al., Eur. J. Clin. Pharmacol., 1990, 38, S108, (pharmacol, isomers)

Bioactivity

PubChem BioAssay

Properties

Product Information

Purity

>98%

≥98% (HPLC)

Salt Data

Free Base

Empirical Formula (Hill Notation)

C24H26N2O4

Certificate of Analysis

Download link

Application(s)

Vasodilator

Pharmacology Properties

Target

adrenergic receptor

Mechanism of Action

Calcium channel blocker

Beta-Adrenoceptor blocker

Molecule

ID:1007