150812-12-7 Usage
Description
Different sources of media describe the Description of 150812-12-7 differently. You can refer to the following data:
1. 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.
2. 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.
Chemical Properties
Purple Solid
Originator
ASTA Medica group (Germany)
Uses
Different sources of media describe the Uses of 150812-12-7 differently. You can refer to the following data:
1. 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).
2. A new experimental anticonvulsant drug. Anxiolytic.
Definition
ChEBI: A substituted aniline that is benzene-1,2,4-triamine bearing ethoxycarbonyl and 4-fluorobenzyl substituents at positions N-1 and N-4 respectively. An anticonvulsant used to treat seizures associated with epilepsy in adults.
Brand name
Trobalt (European Union), Potiga
General Description
Retigabine is an antiepileptic drug, which activates?neuronal KCNQ-type K+ channels by inducing a large hyperpolarizing shift of steady-state?activation.
Biochem/physiol Actions
Retigabine (Ezogabine) is a Kv7.2-7.5 (KCNQ2-5) neuronal potassium channel opener witrh anticonvulsant activity.
Mechanism of action
Retigabine has a novel mechanism of action for an antiseizure drug, acting as positive allosteric modulator of the neuronal potassium channels KNCQ (Kv2 to 5). ?Under normal physiologic conditions, KNCQ channels help establish the ?neuronal resting membrane potential, by providing a continual ?hyperpolarizing influence.
Pharmacology
Retigabine is quickly absorbed, and reaches maximum plasma concentrations between half an hour and 2 hours after a single oral dose. It has a moderately high oral bioavailability (50–60%), a high volume of distribution (6.2?L/kg), and a terminal half-life of 8 to 11 hours. Retigabine requires thrice-daily dosing due to its short half-life.Retigabine is metabolized in the liver, by N-glucuronidation and acetylation. The cytochrome P450 system is not involved. Retigabine and its metabolites are excreted almost completely (84%) by the kidneys.
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.
Synthesis
Commercially available 4-fluorobenzaldehyde (188) was condensed
with 4-amino-2-nitroaniline (189) and the resulting imine
was reduced with sodium borohydride to give aniline 190 in 79–85% yield. Aniline 190 was acylated with
diethylcarbonate (191) to give nitrobenzene 192 in 80–88% yield.
Reduction of the nitro group via catalytic hydrogenation provided
retigabine/ezogabine (XVIII) in 70–90% yield. An alternative method
(not shown) involved initial reduction of nitrobenzene 190 with
Zn/NH4Cl followed by acylation with diethylcarbonate (191) or ethyl chloroformate/Hunig’s base, providing retigabine/ezogabine
(XVIII) in 46–81% overall yield.
Check Digit Verification of cas no
The CAS Registry Mumber 150812-12-7 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,5,0,8,1 and 2 respectively; the second part has 2 digits, 1 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 150812-12:
(8*1)+(7*5)+(6*0)+(5*8)+(4*1)+(3*2)+(2*1)+(1*2)=97
97 % 10 = 7
So 150812-12-7 is a valid CAS Registry Number.
InChI:InChI=1/C16H18FN3O2/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)
150812-12-7Relevant articles and documents
Hydrogen Bond Directed Photocatalytic Hydrodefluorination and Methods of Use Thereof
-
, (2021/01/22)
Methods of synthesizing compounds comprising fluorinated aryl groups are disclosed, wherein said methods utilize hydrogen bond directed photocatalytic hydrodefluorination.
Of retigabine and wherein the intermediate preparation method (by machine translation)
-
, (2020/05/05)
The invention relates to the medicine synthesis field and in particular relates to a preparation method of retigabine and an intermediate thereof. The method specifically comprises the following steps of: (1) preparing a compound with a structure of formula (RET25) by the compound with the structure of formula (RET20) and 4-fluorobenzaldehyde under the action of p-toluene sulfonic acid; (2) preparing the compound with the structure of formula (RET30) by the compound with the structure of formula (RET25) through sodium borohydride reduction; and (3) preparing the retigabine by the compound with the structure of the formula (RET30) through raney nickel hydrogenation reduction. The total impurity content of the retigabine obtained by the preparation method disclosed by the invention is less than 0.16% in terms of area percentage unit of HPLC (High Performance Liquid Chromatography).
PROCESS FOR THE PREPARATION OF AN ANTICONVULSANT COMPOUND
-
, (2014/06/24)
The invention provides a novel method for the preparation of intermediates useful in a process designed to obtain known 1,2,4-triaminobenzene compounds, and in particular a specific compound thereof having known anticonvulsant activity. Unlike known methods, the novel method does not require advance protection of the amino groups present on the substrate.
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