9-oxo-2-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,12,14-hexaene-2-carboxamide

• ChemBase ID: 656
• Molecular Formular: C15H12N2O2
• Molecular Mass: 252.26798
• Monoisotopic Mass: 252.08987763
• SMILES: O=C1Cc2c(N(c3c1cccc3)C(=O)N)cccc2
• Canonical SMILES: O=C1Cc2ccccc2N(c2c1cccc2)C(=O)N
• InChI: InChI=1S/C15H12N2O2/c16-15(19)17-12-7-3-1-5-10(12)9-14(18)11-6-2-4-8-13(11)17/h1-8H,9H2,(H2,16,19)
• InChIKey: CTRLABGOLIVAIY-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 9-oxo-2-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,12,14-hexaene-2-carboxamide; 9-oxo-2-azatricyclo[9.4.0.0^3,^8]pentadeca-1(15),3,5,7,11,13-hexaene-2-carboxamide; 9-oxo-2-azatricyclo[9.4.0.0^3,^8]pentadeca-1(11),3(8),4,6,12,14-hexaene-2-carboxamide
• IUPAC Traditional name: 9-oxo-2-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,12,14-hexaene-2-carboxamide; oxcarbazepine; 9-oxo-2-azatricyclo[9.4.0.0^3,^8]pentadeca-1(11),3(8),4,6,12,14-hexaene-2-carboxamide
• Brand Name: Trileptal
• Synonyms: Oxcarbamazepine; Oxcarbazepine; 10,11-Dihydro-10-oxo-5h-dibenz[b,f]azepine-5-carboxamide; Oxacarbazepine; Oxcarbazepine; 10-oxo-10,11-dihydro-5H-dibenzo[b,f]azepine-5-carboxamide; 10,11-Dihdyro-10-oxo-5H-dibenz[b,f]azepine-5-carboxamide; Aurene; GP 47680; Oxecarb; Oxetol; Trileptal; Oxcarb; 9-oxo-2-azatricyclo[9.4.0.0^{3,8}]pentadeca-1(11),3(8),4,6,12,14-hexaene-2-carboxamide

Database IDs

• CAS Number: 28721-07-5
• EC Number: 249-188-8
• MDL Number: MFCD00865307
• PubChem SID: 46507580; 160964119; 24724563
• PubChem CID: 34312

CALCULATED PROPERTIES

JChem

• Acid pKa: 12.921005
• H Acceptors: 2
• H Donor: 1
• LogD (pH = 5.5): 1.8181766
• LogD (pH = 7.4): 1.8181754
• Log P: 1.8181767
• Molar Refractivity: 71.5579 cm^3
• Polarizability: 27.078526 Å^3
• Polar Surface Area: 63.4 Å^2
• Rotatable Bonds: 0
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 1.76
• LOG S: -3.2
• Solubility (Water): 1.60e-01 g/l

PROPERTIES

Physical Property

• Solubility: 308 mg/L at 25 oC (SRC PhysProp estimated -- MEYLAN,WM et al. (1996)); DMSO: ~9 mg/mL; Methanol
• Apperance: white solid; Yellow Solid
• Melting Point: 215-216°C
• Hydrophobicity(logP): 1.206; 1.5

Safety Information

• Storage Condition: -20°C Freezer, Under Inert Atmosphere
• RTECS: HN8445000
• German water hazard class: 3
• TSCA Listed: 否
• Personal Protective Equipment: Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter

Pharmacology Properties

• Target: Sodium Channel
• Gene Information: rat ... Scnn1g(24768)
• Mechanism of Action: Adenosine-Agonist-A1; Gabaminergic-A; Sodium channel inhibitor; Sympathomimetic-Alpha-2

Product Information

• Purity: ≥98% (HPLC); 95%; 98%
• Salt Data: Free Base
• Application(s): Analgesic; Anticonvulsant; Neuroleptic agent
• Empirical Formula (Hill Notation): C15H12N2O2

DETAILS

DrugBank - DB00776

• Drug Groups: approved
• Description: Oxcarbazepine is structurally a derivative of carbamazepine, adding an extra oxygen atom to the benzylcarboxamide group. This difference helps reduce the impact on the liver of metabolizing the drug, and also prevents the serious forms of anemia occasionally associated with carbamazepine. Aside from this reduction in side effects, it is thought to have the same mechanism as carbamazepine - sodium channel inhibition - and is generally used to treat partial seizures in epileptic children and adults.
• Indication: For use as monotherapy or adjunctive therapy in the treatment of partial seizures in adults with epilepsy and as adjunctive therapy in the treatment of partial seizures in children ages 4-16 with epilepsy.
• Pharmacology: Oxcarbazepine is structurally a derivative of carbamazepine, adding an extra oxygen atom to the benzylcarboxamide group. This difference helps reduce the impact on the liver of metabolizing the drug, and also prevents the serious forms of anemia occasionally associated with carbamazepine. Aside from this reduction in side effects, it is thought to have the same mechanism as carbamazepine - sodium channel inhibition - and is generally used to treat the same conditions.
• Toxicity: Isolated cases of overdose with oxcarbazepine have been reported. The maximum dose taken was approximately 24,000 mg. All patients recovered with symptomatic treatment.
• Affected Organisms: Humans and other mammals
• Biotransformation: Oxcarbazepine is completely absorbed and extensively metabolized to its pharmacologically active 10-monohydroxy metabolite (MHD). MHD is metabolized further by conjugation with glucuronic acid.
• Absorption: Completely absorbed following oral administration. Food has no effect on the rate and extent of absorption of oxcarbazepine.
• Half Life: The half-life of the parent is about 2 hours, while the half-life of MHD is about 9 hours, so that MHD is responsible for most anti-epileptic activity.
• Protein Binding: Approximately 40% of the active 10-monohydroxy metabolite (MHD) is bound to serum proteins, predominantly to albumin. Neither oxcarbazepine nor its MHD binds with alpha-1–acid blycoprotein.
• Elimination: Oxcarbazepine is cleared from the body mostly in the form of metabolites which are predominantly excreted by the kidneys. Fecal excretion accounts for less than 4% of the administered dose.
• Distribution: * 49 L
• References: Mazza M, Della Marca G, Di Nicola M, Martinotti G, Pozzi G, Janiri L, Bria P, Mazza S: Oxcarbazepine improves mood in patients with epilepsy. Epilepsy Behav. 2007 May;10(3):397-401. Epub 2007 Feb 14. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Sigma Aldrich - O3764

Biochem/physiol Actions
Anticonvulsant, antineuralgic. Inhibits veratrine-induced transmitter release.
Other Notes
Tandem Mass Spectrometry data independently generated by Scripps Center for Metabolomics is available to view or download in PDF. O3764.pdf Tested metabolites are featured on Scripps Center for Metabolomics METLIN Metabolite Database. To learn more, visit sigma.com/metlin.

Toronto Research Chemicals - O869250

A metabolite of Eslicarbazepine acetate, (BIA 2-093), a novel central nervous system drug. A keto derivative of Carbamazepine. Used as an anticonvulsant.

REFERENCES

• Mazza M, Della Marca G, Di Nicola M, Martinotti G, Pozzi G, Janiri L, Bria P, Mazza S: Oxcarbazepine improves mood in patients with epilepsy. Epilepsy Behav. 2007 May;10(3):397-401. Epub 2007 Feb 14. Pubmed
• Dam., M., et al.: Epilepsy Res., 3, 70 (1989)
• Beydoun, A., et al.: Expert Opin. Pharmacother., 3, 59 (1989)
• U.K. Pat., 1963, 943 277; CA, 61, 1815f, (synth)
• Ger. Pat., 1970, 2 011 087; CA, 73, 109711r, (deriv, synth, pharmacol)
• Feldmann, K.F. et al., Adv. Epileptol., 1981, 12, 89, (metab)
• Theisohn, M. et al., Eur. J. Clin. Pharmacol., 1982, 22, 545, (metab)
• Kumps, A., J. Liq. Chromatogr., 1984, 7, 1235, (hplc)
• Martindale, The Extra Pharmacopoeia, 30th edn., Pharmaceutical Press, 1993, 301
• Schachter, S.C. et al., Expert Opin. Invest. Drugs, 1999, 8, 1103-1112
• Lohse, O. et al., Tet. Lett., 2001, 42, 385-389, (deriv, synth)