Retigabine

Base Information

• Chemical Name: Retigabine
• CAS No.: 150812-12-7
• Molecular Formula: C16H18FN3O2
• Molecular Weight: 303.336
• European Community (EC) Number: 629-886-2
• UNII: 12G01I6BBU
• DSSTox Substance ID: DTXSID40164615
• Nikkaji Number: J751.646K
• Wikipedia: Retigabine
• Wikidata: Q2146170
• NCI Thesaurus Code: C72839
• Pharos Ligand ID: FRQZ6WHCCCQN
• Metabolomics Workbench ID: 65099
• ChEMBL ID: CHEMBL41355
• Mol file: 150812-12-7.mol

Synonyms:D 20443;D 23129;D-20443;D-23129;ethyl N-(2-amino-4-(4-fluorobenzylamino)phenyl)carbamate hydrochloride;ezogabine;N-(2-amino-4-(4-fluorobenzylamino)phenyl)carbamic acid ethyl ester;Potiga;retigabine

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Chemical Property of Retigabine

Chemical Property:

• Vapor Pressure: 1.34E-07mmHg at 25°C
• Refractive Index: 1.655
• Boiling Point: 430 ºC at 760 mmHg
• PKA: 13.12±0.70(Predicted)
• Flash Point: 213.9 ºC
• PSA: 76.38000
• Density: 1.307 g/cm³
• LogP: 4.31560
• Storage Temp.: room temp
• Solubility.: DMSO: >15mg/mL
• XLogP3: 2.8
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 6
• Exact Mass: 303.13830499
• Heavy Atom Count: 22
• Complexity: 348

Purity/Quality:

Safty Information:

• Pictogram(s): T,N,Xn,F,Xi
• Hazard Codes: T,N,Xn,F,Xi
• Statements: 23-25-50/53-36-20/21/22-11
• Safety Statements: 45-60-61-36/37-16-26

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Anticonvulsants
• Canonical SMILES: CCOC(=O)NC1=C(C=C(C=C1)NCC2=CC=C(C=C2)F)N
• Recent ClinicalTrials: Study to Treat Major Depressive Disorder With a New Medication
• Recent EU Clinical Trials: A Phase 3 Study of Adjunctive XEN496 in Pediatric Subjects with KCNQ2 Developmental and Epileptic Encephalopathy
• Description: Retigabine was approved in March 2011 by the European Commission for the adjunctive treatment of partial-onset seizures in adults who have epilepsy; in June 2011, the U.S. FDA approved the same drug, known in the United States as ezogabine. Retigabine differs from all currently approved antiepileptic drugs in that it acts as a selective positive allosteric modulator (opener) of KCNQ2-5 potassium channels, which are key regulators of neuronal excitability. The discovery of retigabine was based on modification of an analgesic agent flupirtine that had serendipitously shown potent anticonvulsant activity in animal models of epilepsy. Changing a central 2,3,6-triaminopyridine to a 1,2,4-triaminobenzene decreased analgesic activity while enhancing antiepileptic activity. Retigabine (D-23129) was shown to be a broad spectrum anticonvulsant with oral activity in a variety of animal models. The mechanism of action of retigabine was discovered well after its in vivo activity was recognized. Retigabine can be prepared by reductive amination of 2-ethoxycarbonylamino-5-(4-fluorobenzylamino)- nitrobenzene with 4-fluorobenzaldehyde, followed by hydrogenation in the presence of Raney nickel. Retigabine (Item No. 21449) is an analytical reference standard categorized as a positive allosteric modulator (PAM) of KCNQ2-5 (Kv7.2-7.5) potassium ion channels. Formulations containing retigabine have been reported to induce euphoria. Retigabine is regulated as a Schedule V compound in the United States. This product is intended for research and forensic applications.
• Uses: Retigabine may be used as a reference standard in the determination of retigabine in biological matrices using high-performance liquid chromatography coupled with tandem mass spectrometry with positive ion atmospheric pressure chemical ionization (HPLC-APCI-MS/MS). A new experimental anticonvulsant drug. Anxiolytic.
• Clinical Use: Retigabine is an investigational antiepileptic drug with a novel mechanism of action that involves opening of neuronal voltageactivated K+ channels that serves to stabilize the membrane potential and to control neuronal excitability. Thus, retigabine also may prove to be useful in the treatment of other diseases associated with neuronal hyperexcitability.

Technology Process of Retigabine

There total 22 articles about Retigabine 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%

benzyl (4-((ethoxycarbonyl)amino)-3-nitrophenyl)(4-fluorobenzyl)carbamate (1449372-53-5) → Retigabine (150812-12-7)

Guidance literature:

With palladium on activated charcoal; hydrogen; In methanol; at 20 ℃; for 2h;

DOI:10.1021/acs.jmedchem.7b01199

Reference yield: 90.0%

2-ethoxycarbonylamino-5-(4-fluorobenzylamino)nitrobenzene (150812-23-0) → Retigabine (150812-12-7)

Guidance literature:

With hydrogen; 1 % platinum and 2% vanadium on carbon; In ethanol; at 50 - 70 ℃; for 3h; under 1500.15 Torr; Inert atmosphere; Industry scale;

Reference yield: 64.1%

2-ethoxycarbonylamino-5-(4-fluorobenzylideneamino)nitrobenzene (1314406-56-8) → Retigabine (150812-12-7)

Guidance literature:

With palladium 10% on activated carbon; hydrogen; triethylamine; In methanol; at 25 - 30 ℃; under 2250.23 - 3000.3 Torr; Inert atmosphere; Autoclave;

upstream raw materials:

2-nitro-1,4-phenylenediamine

4-fluorobenzaldehyde

retigabine dihydrochloride

2-ethoxycarbonylamino-5-(4-fluorobenzylamino)nitrobenzene

Downstream raw materials:

diethyl 4-(4-fluorobenzylamino)-1,2-phenylenedicarbamate

retigabine dihydrochloride

4-fluorobenzaldehyde

Refernces

• 1、 Kinarivala, Nihar,Patel, Ronak,Boustany, Rose-Mary,Al-Ahmad, Abraham,Trippier, Paul C.. "Discovery of Aromatic Carbamates that Confer Neuroprotective Activity by Enhancing Autophagy and Inducing the Anti-Apoptotic Protein B-Cell Lymphoma 2 (Bcl-2)". . p. 9739 - 9756. Retrieved 2017/12/26.
• 2、 -. "PROCESS FOR THE PREPARATION OF AN ANTICONVULSANT COMPOUND". Paragraph 0042. . Retrieved 2014/06/24.