Rufinamide

Base Information

• Chemical Name: Rufinamide
• CAS No.: 106308-44-5
• Molecular Formula: C₁₀H₈F₂N₄O
• Molecular Weight: 238.197
• Hs Code.: 29339900
• UNII: WFW942PR79
• DSSTox Substance ID: DTXSID1046506
• Nikkaji Number: J575.180B
• Wikipedia: Rufinamide
• Wikidata: Q408565
• NCI Thesaurus Code: C75167
• RXCUI: 69036
• Pharos Ligand ID: 89D44GBLRPKK
• Metabolomics Workbench ID: 149673
• ChEMBL ID: CHEMBL1201754
• Mol file: 106308-44-5.mol

Synonyms:1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxamide;CGP 33101;CGP-33101;Inovelon;rufinamide

Chemical Property of Rufinamide

Chemical Property:

• Appearance/Colour: white powder
• Vapor Pressure: 3.81E-09mmHg at 25°C
• Melting Point: 232-234?C
• Refractive Index: 1.634
• Boiling Point: 473.8 °C at 760 mmHg
• PKA: 14.37±0.50(Predicted)
• Flash Point: 240.4 °C
• PSA: 73.80000
• Density: 1.52 g/cm³
• LogP: 1.40380
• Storage Temp.: −20°C
• Solubility.: DMSO: soluble9mg/mL
• XLogP3: 0.7
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 3
• Exact Mass: 238.06661722
• Heavy Atom Count: 17
• Complexity: 282

Purity/Quality:

99% ^*data from raw suppliers

Rufinamide ^*data from reagent suppliers

Safty Information:

• Pictogram(s): F,T
• Hazard Codes: F,T
• Statements: 11-23/24/25-39/23/24/25-48-41-38-28
• Safety Statements: 7-16-36/37-45-36/37/39-28-26-24/25

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Drug Classes: Anticonvulsants
• Canonical SMILES: C1=CC(=C(C(=C1)F)CN2C=C(N=N2)C(=O)N)F
• Recent ClinicalTrials: An Extended Access Program (EAP) for Participants Who Have Completed Rufinamide Study E2080-G000-303
• Recent EU Clinical Trials: A randomised controlled trial of the ketogenic diet in the treatment of epilepsy in children under the age of two years
• Recent NIPH Clinical Trials: Post-marketing surveillance of long-term administration of Inovelon tablets in patients with Lennox-Gastaut syndrome
• Description: Rufinamide (licensed in 2007) is a third- generation AED known with the proprietary brand name of Invelon?(Eisai, Hatfield) in the UK and USA. Approximately 2.5 million people worldwide are afflicted with epilepsy, a devastating neurological disorder diagnosed by the tendency toward recurrent, unprovoked seizures, often of unknown etiology. Rufinamide has been launched primarily as adjunctive therapy of LGS. Its proposed mechanism of action involves the limitation of firing of sodium-dependent action potentials. The ultimate result is membrane stabilization. Since it does not exhibit measurable binding to monoamine, acetylcholine, histamine, glycine, AMPA/kainate, NMDA, or GABA receptors or systems, these receptor-mediated pathways are not anticipated to be involved in the exertion of rufinamide’s effects. Rufinamide displayed efficacy in several electrical and chemical animal seizure models. Lennox-Gastaut syndrome (LGS) is a severe pediatric epilepsy syndrome characterized by multiple seizure types. Rufinamide is an anticonvulsant. It inhibits the activation of voltage-gated sodium channel 1.1 (Nav1.1) when used at a concentration of 100 μM. Rufinamide inhibits Nav1.1, but not Nav1.2, Nav1.3, and Nav1.6, opening and increases the action potential threshold in primary rat hippocampal neurons. It is an inhibitor of carbonic anhydrase VA (CAVA; Ki = 343.8 nM) that is selective for CAVA over CAI and CAII (Kis = >10,000 nM for both). Rufinamide (100 μM) prolongs the preictal phase and reduces seizure-like event frequency in an in vitro model of epileptiform activity in rat hippocampal slices. It inhibits seizures induced by pentylenetetrazole in a mouse model of epilepsy (ED50 = 54 mg/kg, i.p.) and reduces kainic acid-induced neuronal cell death in the mouse hippocampal CA3 region when used at doses of 25, 50, and 100 mg/kg. Formulations containing rufinamide have been used in the treatment of seizures associated with Lennox-Gastaut Syndrome (LGS).
• Indications: Epilepsy: Adjunctive treatment of Lennox– Gastaut syndrome; refractory tonic/ atonic seizures (unlicensed).
• Uses: Rufinamide, a triazole derivative, is an anticonvulsant medication. It is used in combination with other medication and therapy to treat Lennox–Gastaut syndrome and various other seizure disorders. Rufinamide is presumed to involve stabilization of the so Labelled Rufinamide (R701552). Antiepileptic triazole derivative which decreases firing by neurons at sodium channels. Anticonvulsant. Rufinamide has been used to test its analgesic effect on neuropathic pain in spared nerve injury (SNI) model.
• Clinical Use: Adjunctive treatment of seizures in Lennox-Gastaut syndrome
• Drug interactions: Potentially hazardous interactions with other drugs Antidepressants: antagonism of anticonvulsant effect (convulsive threshold lowered); avoid with St John’s wort. Antimalarials: mefloquine antagonises anticonvulsant effect. Antipsychotics: antagonism of anticonvulsant effect (convulsive threshold lowered). Oestrogens and progestogens: metabolism accelerated by rufinamide - reduced contraceptive effect. Orlistat: possibly increased risk of convulsions with orlistat. Ulipristal: possibly reduces contraceptive effect.

Technology Process of Rufinamide

There total 33 articles about Rufinamide which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 100.0%

2-(azidomethyl)-1,3-difluorobenzene (106308-60-5) + propynoic acid methyl ester (922-67-8) → rufinamide (106308-44-5)

Guidance literature:

2-(azidomethyl)-1,3-difluorobenzene; propynoic acid methyl ester; With copper(ll) sulfate pentahydrate; ascorbic acid; In ethanol; at 20 ℃; for 36h;

With ammonia; In methanol; for 72h;

DOI:10.1021/acs.orglett.6b00512

Reference yield: 95.0%

2-(azidomethyl)-1,3-difluorobenzene (106308-60-5) + 1-[(1-oxo-2-propynyl)oxy]-2,5-pyrrolidinedione (140681-41-0) → rufinamide (106308-44-5)

Guidance literature:

2-(azidomethyl)-1,3-difluorobenzene; 1-[(1-oxo-2-propynyl)oxy]-2,5-pyrrolidinedione; With copper(ll) sulfate pentahydrate; ascorbic acid; In N,N-dimethyl-formamide; for 0.333333h;

With ammonia; In methanol; N,N-dimethyl-formamide; at 0 - 5 ℃; for 0.0833333h; Solvent;

Reference yield: 95.0%

2-propynamide (7341-96-0) + 2,6-Difluorobenzyl bromide (85118-00-9) → rufinamide (106308-44-5)

Guidance literature:

2,6-Difluorobenzyl bromide; With sodium azide; In water; at 60 ℃; for 1h; Green chemistry;

2-propynamide; With (1,10-phenanthroline)bis(triphenylphosphine)copper(I) nitrate; In water; at 60 ℃; for 1h; regioselective reaction; Green chemistry;

DOI:10.1007/s11164-017-2906-7

upstream raw materials:

2-(azidomethyl)-1,3-difluorobenzene

2-Chloroacrylonitrile

CGP 47292

methyl 1-(2,6-difluorobenzyl)-1H-1,2,3-triazole-4-carboxylate

Refernces

• 1、 Singh, Kuldeep,Sarbajna, Abir,Dutta, Indranil,Pandey, Pragati,Bera, Jitendra K.. "Hemilability-Driven Water Activation: A NiII Catalyst for Base-Free Hydration of Nitriles to Amides". . p. 7761 - 7771. Retrieved 2017.
• 2、 Jennah, Oumayma,Beniazza, Redouane,Lozach, Cédric,Jardel, Damien,Molton, Florian,Duboc, Carole,Buffeteau, Thierry,El Kadib, Abdelkrim,Lastécouères, Dominique,Lahcini, Mohammed,Vincent, Jean-Marc. "Photoredox Catalysis at Copper(II) on Chitosan: Application to Photolatent CuAAC". . p. 4615 - 4624. Retrieved 2018.
• 3、 Zhang, Ping,Russell, M. Grace,Jamison, Timothy F.. "Continuous flow total synthesis of rufinamide". . p. 1567 - 1570. Retrieved 2014.
• 4、 Yadav, Suman,Reshi, Noor U Din,Pal, Saikat,Bera, Jitendra K.. "Aerobic oxidation of primary amines to amides catalyzed by an annulated mesoionic carbene (MIC) stabilized Ru complex". . p. 7018 - 7028. Retrieved 2021/11/17.
• 5、 -. "Continuous synthesis method of lulaninamide". Paragraph 0048-0087. . Retrieved 2020/11/11.