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

• ChemBase ID: 1007
• Molecular Formular: C24H26N2O4
• Molecular Mass: 406.47424
• Monoisotopic Mass: 406.18925732
• SMILES: O(c1c2c3c([nH]c2ccc1)cccc3)CC(O)CNCCOc1c(OC)cccc1
• Canonical SMILES: COc1ccccc1OCCNCC(COc1cccc2c1c1ccccc1[nH]2)O
• 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

NAMES AND DATABASE IDS

Names

• IUPAC name: [3-(9H-carbazol-4-yloxy)-2-hydroxypropyl][2-(2-methoxyphenoxy)ethyl]amine
• IUPAC Traditional name: carvedilol; [3-(9H-carbazol-4-yloxy)-2-hydroxypropyl][2-(2-methoxyphenoxy)ethyl]amine
• Brand Name: Coreg; Coreg CR
• Synonyms: Carvedilolum [Latin]; carvedilol; Carvedilol; Coreg; Dilatrend; 1-(9H-Carbazol-4-yloxy)-3-[[2-(2-methoxyphenoxy)ethyl]amino]-2-propanol; BM-14190; Carvedilol; Artist; BM 14190; Cadilan; Carca; Cardivas; Carloc; Carvas; Carvediol; DQ 2466; Dimitone; Eucardic; Korvasan; Kredex; Querto; SKF 105517; Talliton; 1-((9H-carbazol-4-yl)oxy)-3-((2-(2-methoxyphenoxy)ethyl)amino)propan-2-ol

Database IDs

• CAS Number: 72956-09-3
• MDL Number: MFCD00864692
• PubChem SID: 160964470; 46505146
• PubChem CID: 2585

CALCULATED PROPERTIES

JChem

• Acid pKa: 14.030432
• H Acceptors: 5
• H Donor: 3
• LogD (pH = 5.5): 0.48382187
• LogD (pH = 7.4): 2.069334
• Log P: 3.4248545
• Molar Refractivity: 115.6377 cm^3
• Polarizability: 47.905235 Å^3
• Polar Surface Area: 75.74 Å^2
• Rotatable Bonds: 10
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 3.05
• LOG S: -4.96
• Solubility (Water): 4.44e-03 g/l

PROPERTIES

Physical Property

• Solubility: Chloroform; DMSO; DMSO: >20 mg/mL; Methanol; Practically insoluble (0.583 mg/L)
• Apperance: White Solid; white to off-white solid
• Melting Point: 114-115°C
• Hydrophobicity(logP): 3.8

Safety Information

• Storage Condition: -20°C; -20°C Freezer
• Storage Warning: IRRITANT
• RTECS: UA8670000
• European Hazard Symbols: Nature polluting (N)
• UN Number: 3077
• German water hazard class: 3
• Hazard Class: 9
• Packing Group: 3
• Risk Statements: 51/53
• Safety Statements: 61
• TSCA Listed: false
• GHS Pictograms: GHS09
• GHS Hazard statements: H411
• GHS Precautionary statements: P273
• Personal Protective Equipment: Eyeshields, Gloves
• RID/ADR: UN 3077 9/PG 3

Pharmacology Properties

• Target: adrenergic receptor
• Mechanism of Action: Beta-Adrenoceptor blocker; Calcium channel blocker

Product Information

• Purity: >98%; ≥98% (HPLC)
• Salt Data: Free Base
• Application(s): Vasodilator
• Empirical Formula (Hill Notation): C24H26N2O4

DETAILS

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

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]

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.

Toronto Research Chemicals - C184625

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

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
• 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)
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• Ruffolo, R.R. et al., Cardiovasc. Drug Rev., 1992, 10, 127, (rev)
• McTavish, D. et al., Drugs, 1993, 45, 232, (rev)
• Martindale, The Extra Pharmacopoeia, 30th edn., Pharmaceutical Press, 1993, 632
• Beta-blockers in Clinical Practice, (Eds. Cruickshank, J.M. et al), 2nd edn., Churchill Livingstone, 1994, 1119, (book)
• Dunn, C.J., Drugs, 1997, 53, 161-185, (rev)
• Rabasseda, X. et al., Drugs of Today (Barcelona), 1998, 34, 905-926
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