1228076-27-4

Usage

Uses

Used in Pharmaceutical Research:
(4-fluorobenzyl)(6-(morpholin-4-yl)-5-nitropyridin-2-yl)amine is used as a building block for the development of new pharmaceuticals, leveraging the properties of the fluorobenzyl and nitropyridinylamine groups to create novel drug candidates.
Used in Agrochemical Development:
In the agrochemical industry, (4-fluorobenzyl)(6-(morpholin-4-yl)-5-nitropyridin-2-yl)amine is used as an intermediate in the synthesis of new agrochemicals, potentially offering innovative solutions for pest control and crop protection.
Used in Material Science:
(4-fluorobenzyl)(6-(morpholin-4-yl)-5-nitropyridin-2-yl)amine is used as a component in the creation of advanced materials, where its unique structure may contribute to the development of materials with specific properties for various applications.
The precise applications and utility of (4-fluorobenzyl)(6-(morpholin-4-yl)-5-nitropyridin-2-yl)amine will depend on further research and development, as its properties and potential uses are still being explored.

Upstream product

• 1094323-33-7 4-(6-chloro-3-nitropyridin-2-yl)morpholine 
• 140-75-0 para-fluorobenzylamine 

Downstream Products

• 1228076-29-6 N-2-(4-fluorobenzyl)-6-morpholin-4-yl-pyridine-2,5-diamine 
• 1228076-12-7 2-(3,5-difluorophenyl)-N-[6-(4-fluorobenzylamino)-2-(morpholin-4-yl)pyridin-3-yl]acetamide 

Relevant academic research and scientific papers

Flupirtine and retigabine as templates for ligand-based drug design of KV7.2/3 activators

Drug induced liver injury (DILI) and tissue discoloration led to the recent discontinuation of the therapeutic use of the closely related drugs flupirtine and retigabine, respectively. Experience gained with these drugs strongly suggests that heterotetramer, voltage-gated potassium channels 2 and 3 (KV7.2/3) are valid targets for effective treatment of pain and epilepsy. Because the adverse effects are not related to the mechanism of action, it appears promising to investigate chemical modifications of these clinically validated, drug-like leads. In the present retro-metabolic drug design study, a series of 43 compounds were synthesized and characterized with regard to KV7.2/3 opening activity and efficacy. The most active compound 22d displays excellent potency (EC50 = 4 nM) and efficacy (154%) as a KV7.2/3 opener. Limited aqueous solubility hampered toxicity testing at concentrations higher than 63 μM, but this concentration was nontoxic to two hepatocellular cell lines (HEP-G2 and TAMH) in culture. The slightly less active but more soluble compound 25b (EC50 = 11 nM, efficacy 111%) showed an improved toxicity/activity ratio compared to flupirtine by three orders of magnitude and represents an attractive lead structure for the development of safer analgesics and antiepileptics.

Characterization of a novel high-potency positive modulator of K v7 channels

Kv7 channel activators decrease neuronal excitability and might potentially treat neuronal hyperexcitability disorders like epilepsy and mania. Here we introduce NS15370 ((2-(3,5-difluorophenyl)-N-[6-[(4-fluorophenyl) methylamino]-2-morpholino-3-pyridyl]acetamide)hydrochloride, an in vitro high-potency chemical analogue of retigabine, without effects on GABA A receptors. NS15370 activates recombinant homo- and heteromeric Kv7.2-Kv7.5 channels in HEK293 cells at sub-micromolar concentrations (EC50～100 nM, as quantified by a fluorescence based Tl+-influx assay). In voltage clamp experiments NS15370 exhibits a complex, concentration-dependent mode-of-action: At low concentrations it accelerates voltage-dependent activation rates, slows deactivations, and increases steady-state current amplitudes. Quantified by the peak-tail current method, the V12 value of the steady-state activation curve is shifted towards hyperpolarized potentials at concentrations ～100 times lower than retigabine. However, in contrast to retigabine, NS15370 also introduces a distinct time-dependent current decrease, which eventually, at higher concentrations, causes suppression of the current at depolarized potentials, and an apparent cross-over of the voltage-activation curve. In brain slices, NS15370 hyperpolarizes and increases spike frequency adaptation of hippocampal CA1 neurons and the compound reduces the autonomous firing of dopaminergic neurons in the substantia-nigra pars compacta. NS15370 is effective in rodent models of hyperexcitability: (i) it yields full protection against mouse 6 Hz seizures and rat amygdala kindling discharges, two models of partial epilepsia; (ii) it reduces (+)-MK-801 hydrogen maleate (MK-801)-induced hyperactivity as well as chlordiazepoxide (CDP)+d-amphetamine (AMP)-induced hyperactivity, models sensitive to classic anti-psychotic and anti-manic treatments, respectively. Our findings with NS15370 consolidate neuronal Kv7 channels as targets for anti-epileptic and psychiatric drug development.

NOVEL 2-MORPHOLINO-3-AMIDO-PYRIDINE DERIVATIVES AND THEIR MEDICAL USE

The present application discloses novel 2-morpholino-3-amido-pyhcline derivatives and their use as modulators of the voltage gated KV7 (KCNQ) potassium ion channels in the treatment of pain, neurodegenerative disorders, urinary incontinence, etc... In other aspects the application discloses the use of these compounds, in a method for therapy and to pharmaceutical compositions comprising these compounds.