150812-22-9

Usage

Uses

Used in Pharmaceutical Industry:
2-amino-5-(4-fluorobenzylideneamino)nitrobenzene is used as an intermediate in the synthesis of N-Acetyl N-Descarboxyethyl Retigabine (A187930), a metabolite of Retigabine (R189050). Retigabine is an experimental anticonvulsant drug that has shown potential in treating epilepsy by modulating neuronal excitability.
Additionally, 2-amino-5-(4-fluorobenzylideneamino)nitrobenzene may also be used as a building block for the development of anxiolytic drugs, which are medications designed to treat anxiety disorders. Its specific role in this application would depend on the chemical modifications and subsequent drug development processes.

Upstream product

• 5307-14-2 2-nitro-1,4-phenylenediamine 
• 459-57-4 4-fluorobenzaldehyde 

Downstream Products

• 150812-12-7 Retigabine 
• 150812-21-8 1-N-[(4-fluorophenyl)methyl]-3-nitrobenzene-1,4-diamine 
• 150812-23-0 2-ethoxycarbonylamino-5-(4-fluorobenzylamino)nitrobenzene 
• 1587701-31-2 C₂₂H₂₆FN₃O₄ 
• 1432480-98-2 ethyl N-(2-amino-4-{[(4-fluorophenyl)methyl](prop-2-en-1-yl)amino}phenyl)carbamate 
• 1432481-29-2 tert-butyl 2-(tert-butoxycarbonylimino)-4-(N-para-fluorobenzyl-N-allylimino)aniline formate 
• 1432481-28-1 tert-butyl 2-(tert-butoxycarbonylimino)-4-(N-para-fluorobenzylimino)aniline formate 
• 491871-67-1 4-N-[(4-fluorophenyl)methyl]benzene-1,2,4-triamine 
• 1432481-30-5 C₁₆H₁₈FN₃ 
• 1587701-18-5 C₂₇H₃₆FN₃O₄ 

Relevant academic research and scientific papers

Catalyst- And solvent-free efficient access to: N -alkylated amines via reductive amination using HBpin

A sustainable approach which works under catalyst- and solvent-free conditions for the synthesis of structurally diverse secondary amines has been uncovered. This one-pot protocol works efficiently at room temperature and is compatible with a wide range of sterically and electronically diverse aldehydes and primary amines. Notably, this simple process offers scalability, excellent functional group tolerance, chemoselectivity, and is also effective at the synthesis of biologically relevant molecules. This journal is

Discovery of Novel Retigabine Derivatives as Potent KCNQ4 and KCNQ5 Channel Agonists with Improved Specificity

Recent research suggests that KCNQ isoforms, particularly the KCNQ4 and KCNQ5 subtypes expressed in smooth muscle cells, are involved in both establishing and maintaining resting membrane potentials and regulating smooth muscle contractility. Retigabine (

(2-AMINO-4(ARYLAMINO)PHENYL) CARBAMATES

A compound, or pharmaceutically acceptable salt thereof, having a formula (I) wherein R1 is H or optionally-substituted alkyl; R2 is optionally-substituted alkyl; R3 and R4 are each independently H or optionally-substituted alkyl; R5 is H, optionally-substituted alkyl, acyl, or alkoxycarbonyl; R6 and R7 are each independently H, deuterium, optionally- substituted alkyl, or R6 and R7 together form a carbocyclic; R8 is optionally-substituted thiazolyl, optionally-substituted thiophenyl, or substituted phenyl, provided that if R8 is 4-halophenyl, then R2 is substituted alkyl or branched alkyl or at least one of R6 or R7 is not H; and R30, R31 and R32 are each independently H, deuterium, halogen, substituted sulfanyl, or optionally-substituted alkoxy.

Synthesis and evaluation of potent KCNQ2/3-specific channel activators

KQT-like subfamily (KCNQ) channels are voltage-gated, non-inactivating potassium ion channels, and their down-regulation has been implicated in several hyperexcitability-related disorders, including epilepsy, neuropathic pain, and tinnitus. Activators of these channels reduce the excitability of central and peripheral neurons, and, as such, have therapeutic utility. Here, we synthetically modified several moieties of the KCNQ2-5 channel activator retigabine, an anticonvulsant approved by the U.S. Food and Drug Administration. By introducing a CF3-group at the 4-position of the benzylamine moiety, combined with a fluorine atom at the 3-position of the aniline ring, we generated Ethyl (2-amino-3-fluoro-4-((4-(trifluoromethyl)benzyl)amino)phenyl)carbamate (RL648-81), a new KCNQ2/3-specific activator that is >15 times more potent and also more selective than retigabine. We suggest that RL648-81 is a promising clinical candidate for treating or preventing neurologic disorders associated with neuronal hyperexcitability.

PROCESS FOR THE PREPARATION OF RETIGABINE OF THE FORMULA I AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF

The invention relates to process for the preparation of 2-amino-4-(4- fluorobenzylamino)-l-ethoxycarbonylaminobenzene generically known as Retigabine of the formula (I) and its pharmaceutically acceptable salts e.g. Formula IA, particularly to the modification over the prior art processes-I and II disclosed therein in US5384330. The modifications are depicted in the scheme I and scheme II respectively. Disclosed herein are also the novel processes for the preparation of intermediates of formulae M, N and O of the process-I and of formulae R, S, T of process-II, those are used for preparation of Retigabine of the formula I and its pharmaceutically acceptable salts thereof.

Discovery of a retigabine derivative that inhibits KCNQ2 potassium channels

Aim: Retigabine, an activator of KCNQ2-5 channels, is currently used to treat partial-onset seizures. The aim of this study was to explore the possibility that structure modification of retigabine could lead to novel inhibitors of KCNQ2 channels, which were valuable tools for KCNQ channel studies. Methods: A series of retigabine derivatives was designed and synthesized. KCNQ2 channels were expressed in CHO cells. KCNQ2 currents were recorded using whole-cell voltage clamp technique. Test compound in extracellular solution was delivered to the recorded cell using an ALA 8 Channel Solution Exchange System. Results: A total of 23 retigabine derivatives (HN31-HN410) were synthesized and tested electrophysiologically. Among the compounds, HN38 was the most potent inhibitor of KCNQ2 channels (its IC 50 value=0.10±0.05 μmol/L), and was 7-fold more potent than the classical KCNQ inhibitor XE991. Further analysis revealed that HN38 (3 μmol/L) had no detectable effect on channel activation, but accelerated deactivation at hyperpolarizing voltages. In contrast, XE991 (3 μmol/L) did not affect the kinetics of channel activation and deactivation. Conclusion: The retigabine derivative HN38 is a potent KCNQ2 inhibitor, which differs from XE991 in its influence on the channel kinetics. Our study provides a new strategy for the design and development of potent KCNQ2 channel inhibitors.

PROCESS FOR THE PREPARATION OF RETIGABINE

This invention relates to a novel chemical process for the synthesis of 2-ethyoxycarbonylamino-5-(4-fluorobenzylamino)-nitrobenzene and its use in the preparation of 2-amino-4-(4-fluorobenzylamino)-1-ethoxycarbonylaminobenzene (retigabine/ezogabine) and its polymorphic forms thereof.