[(1R,2S,6S,9R)-4,4,11,11-tetramethyl-3,5,7,10,12-pentaoxatricyclo[7.3.0.0^{2,6}]dodecan-6-yl]methyl sulfamate

• ChemBase ID: 158
• Molecular Formular: C12H21NO8S
• Molecular Mass: 339.36204
• Monoisotopic Mass: 339.09878764
• SMILES: S(=O)(=O)(OC[C@]12OC[C@H]3OC(O[C@H]3[C@@H]2OC(O1)(C)C)(C)C)N
• Canonical SMILES: NS(=O)(=O)OC[C@]12OC[C@@H]3[C@H]([C@@H]2OC(O1)(C)C)OC(O3)(C)C
• InChI: InChI=1S/C12H21NO8S/c1-10(2)18-7-5-16-12(6-17-22(13,14)15)9(8(7)19-10)20-11(3,4)21-12/h7-9H,5-6H2,1-4H3,(H2,13,14,15)/t7-,8-,9+,12+/m1/s1
• InChIKey: KJADKKWYZYXHBB-XBWDGYHZSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: [(1R,2S,6S,9R)-4,4,11,11-tetramethyl-3,5,7,10,12-pentaoxatricyclo[7.3.0.0^{2,6}]dodecan-6-yl]methyl sulfamate; [(1R,2S,6S,9R)-4,4,11,11-tetramethyl-3,5,7,10,12-pentaoxatricyclo[7.3.0.0^2,^6]dodecan-6-yl]methyl sulfamate
• IUPAC Traditional name: topiramate
• Brand Name: Topamax; Topamax Sprinkle
• Synonyms: 2,3:4,5-Bis-O-(1-methylethylidene)-β-D-fuctopyranose 1-Sulfamate; Epitoma; Epitomax; TPM; Topamac; Topimax; Topina; Topomax; Topiramatum [INN-Latin]; Topiramic acid; topiramate tablet; Topiramate; Tipiramate [French]; Tipiramato [Spanish]; Topiramato [INN-Spanish]; Topamax; 2,3:4,5-Bis-O-(1-methylethylidene)-36-D-fructo-pyranose sulfamate; McN 4853; RWJ 17021; Topiramate

Database IDs

• CAS Number: 97240-79-4
• MDL Number: MFCD00865320
• PubChem SID: 24724627; 160963621; 46508334
• PubChem CID: 5284627

CALCULATED PROPERTIES

JChem

• Acid pKa: 11.087058
• H Acceptors: 8
• H Donor: 1
• LogD (pH = 5.5): 0.12695874
• LogD (pH = 7.4): 0.12688065
• Log P: 0.12695974
• Molar Refractivity: 72.302 cm^3
• Polarizability: 30.44525 Å^3
• Polar Surface Area: 115.54 Å^2
• Rotatable Bonds: 3
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 1.29
• LOG S: -1.7
• Solubility (Water): 6.80e+00 g/l

PROPERTIES

Physical Property

• Solubility: 9.8 mg/mL; Chloroform; DMSO: ~44 mg/mL; Ethyl Acetate; Hexane; Methanol
• Apperance: white solid; White to Off-White Solid
• Melting Point: 125-126°C
• Hydrophobicity(logP): -0.7

Safety Information

• Storage Condition: -20°C; -20°C Freezer
• RTECS: LS7083000
• European Hazard Symbols: Irritant (Xi)
• German water hazard class: 3
• Risk Statements: 36/37/38
• Safety Statements: 26-36
• GHS Pictograms: GHS07
• GHS Signal Word: Warning
• GHS Hazard statements: H315-H319-H335
• GHS Precautionary statements: P261-P305 + P351 + P338
• Personal Protective Equipment: dust mask type N95 (US), Eyeshields, Gloves
• Storage Temperature: 2-8°C

Pharmacology Properties

• Target: carbonic anhydrase(CA)
• Gene Information: human ... CA1(759), CA2(760), CA4(762), CA5A(763), CA5B(11238), CA9(768)mouse ... Car5a(12352)rat ... Car2(54231), Car4(29242)

Product Information

• Purity: ≥98% (HPLC)
• Salt Data: Free Base
• Empirical Formula (Hill Notation): C12H21NO8S
• Classification: Derivatives & analogs of Natural Compounds

DETAILS

DrugBank - DB00273

• Drug Groups: approved; investigational
• Description: Topiramate (brand name Topamax) is an anticonvulsant drug produced by Ortho-McNeil Neurologics, a division of Johnson & Johnson. It is used to treat epilepsy in both children and adults. In children it is also indicated for treatment of Lennox-Gastaut syndrome (a disorder that causes seizures and developmental delays). It is also Food and Drug Administration (FDA) approved for, and now most frequently prescribed for, the prevention of migraines. [Wikipedia]
• Indication: Used for the treatment and control of partial seizures and severe tonic-clonic (grand mal) seizures and also for the prevention of migraine headaches. In children it is also used for treatment of Lennox-Gastaut syndrome.
• Pharmacology: Topiramate is an anticonvulsant indicated in the treatment of epilepsy and migraine. Topiramate enhances GABA-activated chloride channels. In addition, topiramate inhibits excitatory neurotransmission, through actions on kainate and AMPA receptors. There is evidence that topiramate has a specific effect on GluR5 kainate receptors. It is also an inhibitor of carbonic anhydrase, particular subtypes II and IV, but this action is weak and unlikely to be related to its anticonvulsant actions, but may account for the bad taste and the development of renal stones seen during treatment. Its possible effect as a mood stabilizer seems to occur before anticonvulsant qualities at lower dosages. Topiramate inhibits maximal electroshock and pentylenetetrazol-induced seizures as well as partial and secundarily generalized tonic-clonic seizures in the kindling model, findings predective of a broad spectrum of antiseizure activities clinically.
• Toxicity: Symptoms of overdose include abdominal pain, agitation, blurred vision, convulsions, depression, dizziness, double vision, drowsiness, impaired coordination, impaired mental activity, low blood pressure, reduced consciousness, severe diarrhea, sluggishness, and speech problems.
• Affected Organisms: Humans and other mammals
• Biotransformation: Not extensively metabolized, 70% of the dose is eliminated unchanged in the urine. The other 30% is metabolized hepatically to six metabolites (formed by hydroxylation, hydrolysis, and glucuronidation), none of which constitute more than 5% of an administered dose.
• Absorption: Rapid with pleak plasma concentrations occurring after 2 hours and a bioavailability of 80%.
• Half Life: 19 to 23 hours
• Protein Binding: 15-41% (over the blood concentration range of 0.5 - 250 mg/mL).
• Elimination: Topiramate is not extensively metabolized and is primarily eliminated unchanged in the urine (approximately 70% of an administered dose).
• Clearance: * Oral plasma cl=20 - 30 mL/min [in humans following oral administration]
• References: Blum D, Meador K, Biton V, Fakhoury T, Shneker B, Chung S, Mills K, Hammer A, Isojarvi J: Cognitive effects of lamotrigine compared with topiramate in patients with epilepsy. Neurology. 2006 Aug 8;67(3):400-6. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Selleck Chemicals - S1438

Research Area: Post-traumatic stress disorder, Alcoholism
Biological Activity:
Topiramate is an anticonvulsant drug. The exact mechanism of action is unknown, but four properties that may contribute to topiramate’s antiepileptic and antimigraine efficacy include a blockage of voltage-dependent sodium channels, an augmentation of gamma- aminobutyrate acid activity at some subtypes of the GABA- A receptors, antagonism of AMPA/kainate subtype of the glutamate receptor, and inhibition of the carbonic anhydrase enzyme, particularly isozymes II and IV . [1] 

Sigma Aldrich - T0575

Biochem/physiol Actions
Kainate GluR5 receptor antagonist; anticonvulsant.

Toronto Research Chemicals - T540250

Used as an anticonvulsant.

REFERENCES

• Blum D, Meador K, Biton V, Fakhoury T, Shneker B, Chung S, Mills K, Hammer A, Isojarvi J: Cognitive effects of lamotrigine compared with topiramate in patients with epilepsy. Neurology. 2006 Aug 8;67(3):400-6. Pubmed
• http://en.wikipedia.org/wiki/Topiramate
• Maryanoff, B.E., et al.: J. Med. Chem., 30, 880 (1987)
• Bialer, M.: Clin. Pharmacokinet., 24, 441 (1987)