1,2-benzoxazol-3-ylmethanesulfonamide

• ChemBase ID: 785
• Molecular Formular: C8H8N2O3S
• Molecular Mass: 212.22572
• Monoisotopic Mass: 212.02556313
• SMILES: S(=O)(=O)(N)Cc1noc2c1cccc2
• Canonical SMILES: NS(=O)(=O)Cc1noc2c1cccc2
• InChI: InChI=1S/C8H8N2O3S/c9-14(11,12)5-7-6-3-1-2-4-8(6)13-10-7/h1-4H,5H2,(H2,9,11,12)
• InChIKey: UBQNRHZMVUUOMG-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 1,2-benzoxazol-3-ylmethanesulfonamide; (1,2-benzoxazol-3-yl)methanesulfonamide
• IUPAC Traditional name: zonisamide; 1,2-benzoxazol-3-ylmethanesulfonamide
• Brand Name: Exceglan; Excegram; Excegran; Zonegran
• Synonyms: benzo[d]isoxazol-3-ylmethanesulfonamide; 1,2-benzoxazol-3-ylmethanesulfonamide; Zonisamida [Spanish]; Zonisamidum [Latin]; zonisamide; Zonisamide; Zonegran; 1-(1,2-benzoxazol-3-yl)methanesulphonamide; 1,2-Benzisoxazole-3-methanesulfonamide; 3-(Sulfamoylmethyl)-1,2-benzisoxazole; AD 810; Aleviatin; Excegran; PD 110843; Exegran; Exogran; Fenisoxine; Zonisamide

Database IDs

• CAS Number: 68291-97-4
• MDL Number: MFCD00865316
• PubChem SID: 46505278; 160964248
• PubChem CID: 5734

CALCULATED PROPERTIES

JChem

• Acid pKa: 9.83594
• H Acceptors: 3
• H Donor: 1
• LogD (pH = 5.5): 0.11066865
• LogD (pH = 7.4): 0.10927917
• Log P: 0.11068642
• Molar Refractivity: 50.2984 cm^3
• Polarizability: 21.011 Å^3
• Polar Surface Area: 86.19 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 0.67
• LOG S: -2.01
• Solubility (Water): 2.09e+00 g/l

PROPERTIES

Physical Property

• Solubility: 0.8 mg/mL; DMSO; Ethanol; Ethyl Acetate; Methanol
• Apperance: White to Off-White Solid
• Melting Point: 160-163°C; 163 - 165°C
• Hydrophobicity(logP): -0.363; 0.5

Safety Information

• Storage Condition: -20°C; Refrigerator

Pharmacology Properties

• Mechanism of Action: Binds to sodium channels, voltage sensitive calcium channels and to a lesser extent carbonic anhydrase, this blocks or suppresses neuronal depolarization and hypersynchronization

Product Information

• Purity: 95%; 97%; 98%
• Salt Data: Free Base
• Application(s): Anticonvulsant; Antiepileptic agent

DETAILS

DrugBank - DB00909

• Drug Groups: approved; investigational
• Description: Zonisamide is a sulfonamide anticonvulsant approved for use as an adjunctive therapy in adults with partial-onset seizures. Zonisamide may be a carbonic anhydrase inhibitor although this is not one of the primary mechanisms of action. Zonisamide may act by blocking repetitive firing of voltage-gated sodium channels leading to a reduction of T-type calcium channel currents, or by binding allosterically to GABA receptors. This latter action may inhibit the uptake of the inhibitory neurotransmitter GABA while enhancing the uptake of the excitatory neurotransmitter glutamate.
• Indication: For use as adjunctive treatment of partial seizures in adults with epilepsy.
• Pharmacology: Zonisamide is an antiseizure drug chemically classified as a sulfonamide and unrelated to other antiseizure agents. The precise mechanism by which zonisamide exerts its antiseizure effect is unknown, although it is believed that the drug blocks sodium and calcium channels, which leads to the suppression of neuronal hypersynchronization (i.e. convulsions). Sonisamide has also been found to potentiate dopaminergic and serotonergic neurotransmission but does not appear to potentiate syanptic activity by GABA (gamma amino butyric acid).
• Toxicity: Symptoms of overdose include diminished breathing, loss of consciousness, low blood pressure, and slow heartbeat.
• Affected Organisms: Humans and other mammals
• Biotransformation: Primarily hepatic through cytochrome P450 isoenzyme 3A4 (CYP3A4). Undergoes acetylation and reduction, forming N-acetyl zonisamide, and the open-ring metabolite 2–sulfamoylacetyl phenol, respectively.
• Absorption: Variable, yet relatively rapid rate of absorption with a time to peak concentration of 2.8-3.9 hours. Food has no effect on the bioavailability of zonisamide.
• Half Life: 63 hours
• Protein Binding: 40% (at concentrations of 1.0-7.0 µg/mL)
• Elimination: Zonisamide is excreted primarily in urine as parent drug and as the glucuronide of a metabolite.
• Distribution: * 1.45 L/kg
• Clearance: * 0.30 - 0.35 mL/min/kg [patients not receiving enzyme-inducing antiepilepsy drugs (AEDs)]; * 0.35 - 0.5 mL/min/kg [Concomitant administration of phenytoin and carbamazepine]
• References: Murata M, Horiuchi E, Kanazawa I: Zonisamide has beneficial effects on Parkinson's disease patients. Neurosci Res. 2001 Dec;41(4):397-9. [Pubmed] ; Gadde KM, Franciscy DM, Wagner HR 2nd, Krishnan KR: Zonisamide for weight loss in obese adults: a randomized controlled trial. JAMA. 2003 Apr 9;289(14):1820-5. [Pubmed] ; Hasegawa H: Utilization of zonisamide in patients with chronic pain or epilepsy refractory to other treatments: a retrospective, open label, uncontrolled study in a VA hospital. Curr Med Res Opin. 2004 May;20(5):577-80. [Pubmed] ; Leppik IE: Zonisamide: chemistry, mechanism of action, and pharmacokinetics. Seizure. 2004 Dec;13 Suppl 1:S5-9; discussion S10. [Pubmed] ; Ueda Y, Doi T, Tokumaru J, Willmore LJ: Effect of zonisamide on molecular regulation of glutamate and GABA transporter proteins during epileptogenesis in rats with hippocampal seizures. Brain Res Mol Brain Res. 2003 Aug 19;116(1-2):1-6. [Pubmed] ; Farooq MU, Moore PW, Bhatt A, Aburashed R, Kassab MY: Therapeutic role of zonisamide in neuropsychiatric disorders. Mini Rev Med Chem. 2008 Sep;8(10):968-75. [Pubmed] ; Schulze-Bonhage A: Zonisamide in the treatment of epilepsy. Expert Opin Pharmacother. 2010 Jan;11(1):115-26. [Pubmed] ; Kothare SV, Kaleyias J: Zonisamide: review of pharmacology, clinical efficacy, tolerability, and safety. Expert Opin Drug Metab Toxicol. 2008 Apr;4(4):493-506. [Pubmed] ; Peters DH, Sorkin EM: Zonisamide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in epilepsy. Drugs. 1993 May;45(5):760-87. [Pubmed] ; Sobieszek G, Borowicz KK, Kimber-Trojnar Z, Malek R, Piskorska B, Czuczwar SJ: Zonisamide: a new antiepileptic drug. Pol J Pharmacol. 2003 Sep-Oct;55(5):683-9. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Selleck Chemicals - S1445

Research Area: Obesity
Biological Activity:
Zonisamide is a sulfonamide anticonvulsant approved for use as an adjunctive therapy in adults with partial-onset seizures for adults; infantile spasm, mixed seizure types of Lennox-Gastaut syndrome, myoclonic, and generalized tonic clonic seizure. [1]

Toronto Research Chemicals - Z700000

Sulfonamide antiseizure agent; blocks repetitive firing of voltagesensitive sodium channels and reduces voltage-sensitive T-type calcium currents. Heterocyclic methanesulfonide with anticonvulsant properties. The compound is under investigation for potent

REFERENCES

• Murata M, Horiuchi E, Kanazawa I: Zonisamide has beneficial effects on Parkinson's disease patients. Neurosci Res. 2001 Dec;41(4):397-9. Pubmed
• Gadde KM, Franciscy DM, Wagner HR 2nd, Krishnan KR: Zonisamide for weight loss in obese adults: a randomized controlled trial. JAMA. 2003 Apr 9;289(14):1820-5. Pubmed
• Hasegawa H: Utilization of zonisamide in patients with chronic pain or epilepsy refractory to other treatments: a retrospective, open label, uncontrolled study in a VA hospital. Curr Med Res Opin. 2004 May;20(5):577-80. Pubmed
• Leppik IE: Zonisamide: chemistry, mechanism of action, and pharmacokinetics. Seizure. 2004 Dec;13 Suppl 1:S5-9; discussion S10. Pubmed
• Ueda Y, Doi T, Tokumaru J, Willmore LJ: Effect of zonisamide on molecular regulation of glutamate and GABA transporter proteins during epileptogenesis in rats with hippocampal seizures. Brain Res Mol Brain Res. 2003 Aug 19;116(1-2):1-6. Pubmed
• Farooq MU, Moore PW, Bhatt A, Aburashed R, Kassab MY: Therapeutic role of zonisamide in neuropsychiatric disorders. Mini Rev Med Chem. 2008 Sep;8(10):968-75. Pubmed
• Schulze-Bonhage A: Zonisamide in the treatment of epilepsy. Expert Opin Pharmacother. 2010 Jan;11(1):115-26. Pubmed
• Kothare SV, Kaleyias J: Zonisamide: review of pharmacology, clinical efficacy, tolerability, and safety. Expert Opin Drug Metab Toxicol. 2008 Apr;4(4):493-506. Pubmed
• Peters DH, Sorkin EM: Zonisamide. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in epilepsy. Drugs. 1993 May;45(5):760-87. Pubmed
• Sobieszek G, Borowicz KK, Kimber-Trojnar Z, Malek R, Piskorska B, Czuczwar SJ: Zonisamide: a new antiepileptic drug. Pol J Pharmacol. 2003 Sep-Oct;55(5):683-9. Pubmed
• http://en.wikipedia.org/wiki/Zonisamide
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