Retigabine 2HCl - ≥99% , CAS No.150812-13-8

CAS: 150812-13-8 Cat. No.: R413173 Formula: C₁₆H₂₀Cl₂FN₃O₂ Peso molecolare: 376.25 PubChem CID: 6918229

GRADE & PURITY ≥99%

Synonyms

BR164335 | E98674 | HY-15471A | Benzoic acid,5-dimethoxy-, methyl ester | Retigabine hydrochloride | D23129 | N-(2-amino-4-[fluorobenzylamino]-phenyl) carbamic acid (2HCl) | Retigabine 2HCl | UNII-WV9W9019AP | SCHEMBL155918 | CCG-268364 | BCP07747 | HE-02

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Panoramica

Information

Retigabine 2HCl Retigabine 2HCl (D-23129) is a novel anticonvulsant with activity in a broad range of seizure models. The mechanism of action involves opening of neuronal K(V)7.2-7.5 (formerly KCNQ2-5) voltage-activated K(+) channels.

Targets

KCNQ3/5 (Cell-based assay); KCNQ2/Q3 channels (Cell-based assay); KCQN4 (Cell-based assay) 1.4 μM(EC50); 1.6 μM(EC50); 5.2 μM(EC50)

In vitro

Retigabine is a novel antiepileptic drug whose mechanism of action involves potassium channel opening activity in neuronal cells. Retigabine can markedly enhance KCNQ2/Q3 currents. In addition, retigabine also enhances slow channel deactivation. Retigabine has been shown to increase the synthesis of GABA in rat hippocampal slices and to enhance GABA-induced chloride currents in cultured rat cortical neurons. Retigabine has been shown to induce membrane hyperpolarization in neurones in rat hippocampal-entorhinal cortex slices and to exert potassium channel opening activity in neuronal cells. Retigabine enhances a linopirdine-sensitive current in differentiated PC12 cells. concentrations of RTG/EZG ≥10 μM are required to cause significant augmentation of the GABAA receptor response. The potency of RTG/EZG differs somewhat depending on the GABAA receptor subunit combination, with the following rank order: α1β3γ2=α1β2γ2 >α3β2γ2=α2β2γ2>α5β2γ2=α1β2(N265S)γ2=α1β1γ2. RTG/EZG exhibits only weak inhibitory effects at voltage-gated Nav and Cav channel currents at predominantly supratherapeutic concentrations. RTG/EZG does not interact significantly with glutamate receptors.

In vivo

Retigabine enhances γ-aminobutyric acid (GABA)-ergic transmission in the central nervous system. Retigabine is rapidly absorbed and distributed with an oral bioavailability of 60% and a high volume of distribution of approximately 6.2 L/kg. Tolerability is good in humans when titrated up to its therapeutic dose range (600-1200 mg/day). Plasma protein binding of the drug is approximately 80%. The relatively high systemic bioavailability after oral administration suggests that retigabine is resistant to first-pass metabolism, a finding confirmed in multiple species. Retigabine is metabolized exclusively via phase II hepatic glucuronidation and acetylation. Gender differences in exposure have been noted, with female subjects exhibiting higher plasma concentrations of the drug after oral administration than male subjects. Excretion of retigabine appears to be predominantly renal. Depending on the behavioral endpoints analyzed, it appears that retigabine has a relatively poor therapeutic index (ratio between TD50 obtained in rotarod and ED50 obtained in maximal electroshock where maximal tonic extension of the hindlimbs was used as endpoint) in both mice (TD50/ED50 = 2.2) and rats (TD50/ED50 = 1.9) after i.p. administration. However, after p.o. administration in rats retigabine shows a therapeutic index of 28.8, which compares favorably with that reported for other antiepileptics, such as carbamazepine.

Cell Research(from reference)

Cell lines：HEK293 cells 

Concentrations：0.1, 0.3, 1 or 3\u2009μM 

Incubation Time：4 h 

Specifications

Sinonimi

BR164335 | E98674 | HY-15471A | Benzoic acid,5-dimethoxy-, methyl ester | Retigabine hydrochloride | D23129 | N-(2-amino-4-[fluorobenzylamino]-phenyl) carbamic acid (2HCl) | Retigabine 2HCl | UNII-WV9W9019AP | SCHEMBL155918 | CCG-268364 | BCP07747 | HE-02

Specifiche e purezza

≥99%

Meccanismi biochimici e fisiologici

Retigabine 2HCl (D-23129) is a novel anticonvulsant with activity in a broad range of seizure models. The mechanism of action involves opening of neuronal K(V)7.2-7.5 (formerly KCNQ2-5) voltage-activated K(+) channels.

Condizioni di conservazione di stoccaggio

Store at -20°C

Spedito in

Ice chest + Ice pads

Questo prodotto richiede spedizione a catena fredda. I servizi di terra e altri servizi economici non sono disponibili.

Purezza

≥99%

Nomi e identificatori

Pubchem Sid

504764354

Pubchem Sid Url

https://pubchem.ncbi.nlm.nih.gov/substance/504764354

Sorrisi canonici

CCOC(=O)NC1=C(C=C(C=C1)NCC2=CC=C(C=C2)F)N.Cl.Cl

IUPAC Name

ethyl N-[2-amino-4-[(4-fluorophenyl)methylamino]phenyl]carbamate;dihydrochloride

InChIKey

WSGFOWNASITQHJ-UHFFFAOYSA-N

INCHI

1S/C16H18FN3O2.2ClH/c1-2-22-16(21)20-15-8-7-13(9-14(15)18)19-10-11-3-5-12(17)6-4-11;;/h3-9,19H,2,10,18H2,1H3,(H,20,21);2*1H

Isomeri SMILES

CCOC(=O)NC1=C(C=C(C=C1)NCC2=CC=C(C=C2)F)N.Cl.Cl

PubChem CID

6918229

Peso molecolare

376.25

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Classe Benzene and substituted derivatives
      • Subclass Phenylmethylamines

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Classe: Benzene and substituted derivatives
• Subclass: Phenylmethylamines
• Intermediate Tree Nodes: Not available
• Direct Parent: Phenylbenzamines
• Alternative Parents: Phenylcarbamic acid esters Phenylalkylamines Benzylamines Aniline and substituted anilines Secondary alkylarylamines Fluorobenzenes Aryl fluorides Carbamate esters Primary amines Organofluorides Organic oxides Hydrochlorides Hydrocarbon derivatives Carbonyl compounds
• Molecular Framework: Aromatic homomonocyclic compounds
• Substituents: Phenylbenzamine - Phenylcarbamic acid ester - Benzylamine - Aniline or substituted anilines - Phenylalkylamine - Fluorobenzene - Halobenzene - Secondary aliphatic/aromatic amine - Aralkylamine - Aryl halide - Aryl fluoride - Carbamic acid ester - Secondary amine - Hydrocarbon derivative - Primary amine - Organooxygen compound - Organonitrogen compound - Organofluoride - Organohalogen compound - Amine - Carbonyl group - Organic nitrogen compound - Hydrochloride - Organic oxygen compound - Organic oxide - Aromatic homomonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as phenylbenzamines. These are aromatic compounds consisting of a benzyl group that is N-linked to a benzamine.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Proprietà chimiche e fisiche

• Solubilità: Solubility (25°C) In vitro DMSO: 75 mg/mL (199.33 mM); Water: 75 mg/mL (199.33 mM); Ethanol: 25 mg/mL (66.44 mM)
• Peso molecolare: 376.200 g/mol
• Hydrogen Bond Donor Count: 5
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 6
• Exact Mass: 375.092 Da
• Monoisotopic Mass: 375.092 Da
• Topological Polar Surface Area: 76.400 Ų
• Heavy Atom Count: 24
• Formal Charge: 0
• Complexity: 348.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 3

XLogP3