241.2884| Heterocyclic Building Blocks-quinoxaline

Le, Alexander M. et al. published their research in Anesthesiology in 2014 | CAS: 154235-83-3

Piperidin-1-yl(quinoxalin-6-yl)methanone (cas: 154235-83-3) belongs to quinoxaline derivatives. Quinoxalines have received a significant amount of attention due to their potential use in fighting various pathophysiological conditions like epilepsy, Parkinson’s, and Alzheimer’s diseases. They are well-known for application in organic light emitting devices, polymers and pharmaceutical agents. The quinoxaline-containing polymers are applicable in optical devices due to their thermal stability and low band gap.Synthetic Route of C14H15N3O

AMPAkines Have Novel Analgesic Properties in Rat Models of Persistent Neuropathic and Inflammatory Pain was written by Le, Alexander M.;Lee, Michelle;Su, Chen;Zou, Anthony;Wang, Jing. And the article was included in Anesthesiology in 2014.Synthetic Route of C14H15N3O This article mentions the following:

Background: Novel analgesics that do not suppress the respiratory drive are urgently needed. Glutamate signaling through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors plays important roles in central pain circuits. AMPAkines augment AMPA receptor function and have been shown to stimulate the respiratory drive to oppose opioid-induced hypoventilation. However, their role in chronic pain states remains unknown. Methods: The authors studied AMPAkines (CX546 and CX516) in rat spared nerve injury (SNI) model of neuropathic pain and Complete Freund’s Adjuvant (CFA) model of inflammatory pain. They measured the effect of AMPAkines on mech. and cold allodynia. They also evaluated their effect on depressive symptoms of pain using the forced swim test, as time of immobility on this test has been used as a measure for behavioral despair, a feature of depression. Results: The authors found that CX546, compared with DMSO (DMSO) control, reduced both mech. and sensory allodynia in SNI (DMSO group, n = 9; CX546 group, n = 11) and CFA models (both DMSO and CX546 groups, n = 9). They found that CX546, compared with control, also reduced depressive symptoms of pain by decreasing immobility on the forced swim test in both SNI (both DMSO and CX546 groups, n = 8) and CFA models (both DMSO and CX546 groups, n = 10). Finally, they found that CX516, compared with control, also reduced mech. and cold allodynia in the SNI model (both DMSO and CX516 groups, n = 10). Conclusions: AMPAkines alleviate pain hypersensitivity as well as depression-like behavior associated with long-lasting nerve injury and inflammatory insult. In the experiment, the researchers used many compounds, for example, Piperidin-1-yl(quinoxalin-6-yl)methanone (cas: 154235-83-3Synthetic Route of C14H15N3O).

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Singh, Surendra P. et al. published their research in CNS Drugs in 2011 | CAS: 154235-83-3

Piperidin-1-yl(quinoxalin-6-yl)methanone (cas: 154235-83-3) belongs to quinoxaline derivatives. Compounds possessing quinoxaline derivatives were bestowed with a variety of significant biological properties such as antiviral, antimalarial, anticancer, DNA intercalation, DNA duplex stabilization, and many others. Modifying quinoxaline structure it is possible to obtain a wide variety of biomedical applications, namely antimicrobial activities and chronic and metabolic diseases treatment.COA of Formula: C14H15N3O

Meta-analysis of the efficacy of adjunctive NMDA receptor modulators in chronic schizophrenia was written by Singh, Surendra P.;Singh, Vidhi. And the article was included in CNS Drugs in 2011.COA of Formula: C14H15N3O This article mentions the following:

Background: Based on the glutamatergic NMDA receptor hypofunction theory of schizophrenia, NMDA receptor modulators (NMDARMs) may have therapeutic potential in the treatment of schizophrenia. Objective: This meta-anal. aimed to evaluate the potential of modulators of the NMDA receptor as adjunctive therapy for schizophrenia, using the results from published trials. Data Sources: A primary electronic search for controlled clin. trials using NMDARMs in schizophrenia was conducted on the PubMed, Cochrane Library, EMBASE, CINAHL and PsycINFO databases. A secondary manual search of references from primary publications was also performed. Study Selection: Inclusion criteria were the application of an established method of diagnosis, randomized case assignment, comparison of NMDARM add-on therapy with placebo, and double-blind assessment of symptoms in chronic schizophrenia using standardized rating scales. Results were based on a total sample size of 1253 cases from 29 trials that fulfilled the specified criteria. Data Extraction: Scores on rating scales or on their relevant subscales were obtained for all selected studies from published results for the min. dataset to compute the difference between post- and pre-trial scores and their pooled standard deviation for NMDARM add-on therapy and placebo groups for neg., pos. and total symptoms. Results: A neg. standardized mean difference (SMD) indicates therapeutic benefit in favor of NMDARM add-on therapy and all SMD results mentioned here are statistically significant. The overall effect size for NMDARMs as a group was small for neg. (SMD -0.27) and medium for total (SMD -0.40) symptoms of chronic schizophrenia. Subgroup anal. revealed medium effect sizes for D-serine and N-acetyl-cysteine (NAC) for neg. (SMD -0.53 and -0.45, resp.) and total (SMD -0.40 and -0.64, resp.) symptoms, and for glycine (SMD -0.66) and sarcosine (SMD -0.41) for total symptoms. As adjuvants to non-clozapine antipsychotics, addnl. therapeutic benefits were observed for NMDARM as a group (SMD -0.14) and glycine (SMD -0.54) for pos. symptoms; D-serine (SMD -0.54), NAC (SMD -0.45) and sarcosine (SMD -0.39) for neg. symptoms; and NMDARM as a group (SMD -0.38), D-serine (SMD -0.40), glycine (SMD -1.12), NAC (SMD -0.64) and sarcosine (SMD -0.53) for total symptoms. When added to clozapine, none of the drugs demonstrated therapeutic potential, while addition of glycine (SMD +0.56) worsened pos. symptoms. Conclusions: Taking into consideration the number of trials and sample size in subgroup analyses, D-serine, NAC and sarcosine as adjuncts to non-clozapine antipsychotics have therapeutic benefit in the treatment of neg. and total symptoms of chronic schizophrenia. While glycine improves pos. and total symptoms as an adjuvant to non-clozapine antipsychotics, it worsens them when added to clozapine. In the experiment, the researchers used many compounds, for example, Piperidin-1-yl(quinoxalin-6-yl)methanone (cas: 154235-83-3COA of Formula: C14H15N3O).

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Danysz, W. et al. published their research in Current Opinion in Central & Peripheral Nervous System Investigational Drugs in 1999 | CAS: 154235-83-3

Piperidin-1-yl(quinoxalin-6-yl)methanone (cas: 154235-83-3) belongs to quinoxaline derivatives. Condensed heterocycles of quinoxalines have become attractive targets in synthetic and medicinal chemistry due to their significant biological activities. Quinoxalines are used in the treatment of bacterial, cancer, and HIV infections. Moreover, varenicline, a clinical drug is used for treating nicotine addiction, also contains quinoxaline moiety.Safety of Piperidin-1-yl(quinoxalin-6-yl)methanone

CX-516 Cortex Pharmaceuticals Inc was written by Danysz, W.. And the article was included in Current Opinion in Central & Peripheral Nervous System Investigational Drugs in 1999.Safety of Piperidin-1-yl(quinoxalin-6-yl)methanone This article mentions the following:

A review with many references CX-516, an AMPA modulator from Cortex Pharmaceuticals, is in phase I/IIa clin. trials for the symptomatic treatment of deficits in memory and cognition in Alzheimer’s disease (AD) and similar disorders. CX-516 and other members in the series are also being investigated for possible antidepressant and antipsychotic activity. Results from initial studies showed that CX-691 and CX-519, both members of the AMP Akine family, have antidepressant activities. In Jan. 1999, Cortex licensed AMP Akine technol. rights to Organon for schizophrenia and depression. Cortex entered into a Cooperative Research and Development Agreement (CRADA) with the National Institute of Neurol. Diseases and Stroke, National Institutes of Health, for the initial clin. evaluation of CX-516 in AD patients in Nov. 1996. The results of a trial of CX-516 in combination with clozapine in schizophrenia patients were presented at the International Society for Schizophrenia Research in Apr. 1999. CX-516 improved a number of aspects of cognitive function. In the experiment, the researchers used many compounds, for example, Piperidin-1-yl(quinoxalin-6-yl)methanone (cas: 154235-83-3Safety of Piperidin-1-yl(quinoxalin-6-yl)methanone).

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Sirvio, J. et al. published their research in Neuroscience (Oxford) in 1996 | CAS: 154235-83-3

Piperidin-1-yl(quinoxalin-6-yl)methanone (cas: 154235-83-3) belongs to quinoxaline derivatives. Quinoxalines have received a significant amount of attention due to their potential use in fighting various pathophysiological conditions like epilepsy, Parkinson鈥檚, and Alzheimer鈥檚 diseases. The parent substance of the group, quinoxaline, results when glyoxal is condensed with 1,2-diaminobenzene. Substituted derivatives arise when 伪-ketonic acids, 伪-chlorketones, 伪-aldehyde alcohols and 伪-ketone alcohols are used in place of diketones.Electric Literature of C14H15N3O

Effects of pharmacologically facilitating glutamatergic transmission in the trisynaptic intrahippocampal circuit was written by Sirvio, J.;Larson, J.;Quach, C. N.;Rogers, G. A.;Lynch, G.. And the article was included in Neuroscience (Oxford) in 1996.Electric Literature of C14H15N3O This article mentions the following:

The effects of a recently synthesized benzoyl-piperidine drug that enhances currents mediated by 伪-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-type glutamate receptors were tested on monosynaptic and polysynaptic responses in hippocampal slices of the rat. Stimulation of perforant path inputs to the dentate gyrus evoked extracellular responses in field CA1 that had latencies and laminar profiles indicating that they were relayed through the trisynaptic intrahippocampal circuit. Under control conditions, trisynaptic field excitatory postsynaptic potentials did not show larger pair-pulse facilitation than monosynaptic responses and failed to exhibit frequency facilitation. Low concentrations of picrotoxin greatly enhanced trisynaptic responses and, under these conditions, frequency facilitation was obtained. Benzoyl-piperidine-12 (250 渭M) had a three-fold greater effect on the amplitude of trisynaptic responses than on monosynaptic field excitatory postsynaptic potentials, indicating that the drug’s effect is amplified across the successive stages of a polysynaptic circuit. The AMPA receptor modulator did not change the frequency characteristics of monosynaptic potentials and had only a modest influence on those of the trisynaptic response. The effect of benzoyl-piperidine-12 on trisynaptic responses was significantly greater when GABAergic inhibition was partially blocked with picrotoxin; the GABA blocker did not alter the effects of benzoyl-piperidine-12 on monosynaptic responses. These results indicate that centrally active AMPA receptor modulators are likely to have a greater influence on brain operations involving long chains of connections than on those mediated by simple reflex-like circuits, and will vary markedly in their effects depending upon the excitability of local interneurons. In the experiment, the researchers used many compounds, for example, Piperidin-1-yl(quinoxalin-6-yl)methanone (cas: 154235-83-3Electric Literature of C14H15N3O).

Piperidin-1-yl(quinoxalin-6-yl)methanone (cas: 154235-83-3) belongs to quinoxaline derivatives. Quinoxalines have received a significant amount of attention due to their potential use in fighting various pathophysiological conditions like epilepsy, Parkinson鈥檚, and Alzheimer鈥檚 diseases. The parent substance of the group, quinoxaline, results when glyoxal is condensed with 1,2-diaminobenzene. Substituted derivatives arise when 伪-ketonic acids, 伪-chlorketones, 伪-aldehyde alcohols and 伪-ketone alcohols are used in place of diketones.Electric Literature of C14H15N3O

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Patel, Nandini C. et al. published their research in Journal of Medicinal Chemistry in 2013 | CAS: 154235-83-3

Piperidin-1-yl(quinoxalin-6-yl)methanone (cas: 154235-83-3) belongs to quinoxaline derivatives. Quinoxaline is isomeric with other naphthyridines including quinazoline, phthalazine and cinnoline. They are well-known for application in organic light emitting devices, polymers and pharmaceutical agents. The quinoxaline-containing polymers are applicable in optical devices due to their thermal stability and low band gap.Formula: C14H15N3O

Discovery and Characterization of a Novel Dihydroisoxazole Class of 伪-Amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) Receptor Potentiators was written by Patel, Nandini C.;Schwarz, Jacob;Hou, Xinjun J.;Hoover, Dennis J.;Xie, Longfei;Fliri, Anton J.;Gallaschun, Randall J.;Lazzaro, John T.;Bryce, Dianne K.;Hoffmann, William E.;Hanks, Ashley N.;McGinnis, Dina;Marr, Eric S.;Gazard, Justin L.;Hajos, Mihaly;Scialis, Renato J.;Hurst, Raymond S.;Shaffer, Christopher L.;Pandit, Jayvardhan;O’Donnell, Christopher J.. And the article was included in Journal of Medicinal Chemistry in 2013.Formula: C14H15N3O This article mentions the following:

Pos. allosteric modulators (“potentiators”) of 伪-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors (AMPAR) enhance excitatory neurotransmission and may improve the cognitive deficits associated with various neurol. disorders. The dihydroisoxazole (DHI) series of AMPAR potentiators described herein originated from the identification of one compound by a high-throughput functional activity screen using mouse embryonic stem (mES) cell-derived neuronal precursors. Subsequent structure-based drug design using X-ray crystal structures of the ligand-binding domain of human GluA2 led to the discovery of both PF-04725379, which in tritiated form became a novel ligand for characterizing the binding affinities of subsequent AMPAR potentiators in rat brain homogenate, and PF-04701475 , a prototype used to explore AMPAR-mediated pharmacol. in vivo. Lead series optimization provided a functionally potent compound lacking the potentially bioactivatable aniline within another compound, but retaining desirable in vitro ADME properties. In the experiment, the researchers used many compounds, for example, Piperidin-1-yl(quinoxalin-6-yl)methanone (cas: 154235-83-3Formula: C14H15N3O).

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Munirathinam, Subramani et al. published their research in Toxicology and Applied Pharmacology in 2002 | CAS: 154235-83-3

Piperidin-1-yl(quinoxalin-6-yl)methanone (cas: 154235-83-3) belongs to quinoxaline derivatives. Quinoxaline derivatives are important constituents of pharmacologically active compounds, including antibacterial, antibiotic and antineoplastic, antifungal, anti-inflammatory and analgesic drugs. Quinoxaline-1,4-di-N-oxide derivatives have shown to improve the biological results and are endowed with anti-viral, anti-cancer, anti-bacterial, and anti-protozoal activities with application in many other therapeutic areas.Category: quinoxaline

Positive Modulation of 伪-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid-Type Glutamate Receptors Elicits Neuroprotection after Trimethyltin Exposure in Hippocampus was written by Munirathinam, Subramani;Rogers, Gary;Bahr, Ben A.. And the article was included in Toxicology and Applied Pharmacology in 2002.Category: quinoxaline This article mentions the following:

The 伪-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamatergic receptors have been linked to survival signaling, especially when the receptors are allosterically modulated by members of the Ampakine family. While increased glutamatergic communication through AMPA receptors has been shown to protect against toxic conditions that target hippocampal subfield CA1, protection in other subfields has not been shown. Accordingly, pos. modulation of AMPA receptors by Ampakine compounds CX727 and CX516 was tested for effects on trimethyltin (TMT) neurotoxicity in rat hippocampal slice cultures. TMT was applied for 4 h followed by a rapid washout and antagonistic quenching of AMPA and N-methyl-d-aspartate (NMDA) receptors. After a 24-h period, the TMT-exposed slices exhibited increased levels of calpain-mediated spectrin breakdown as well as synaptic deterioration. TMT selectively targeted CA3 pyramidal neurons and dentate gyrus (DG) granule cells as evidenced by degeneration and neuronal loss. The cytoskeletal and synaptic damage was reduced when Ampakine modulation was initiated during the postinsult period. Furthermore, the extent of protection was comparable to that produced by the NMDA receptor antagonist AP5. The above results were substantiated by histol. experiments, revealing that Ampakine treatment prevented TMT-induced cell loss in CA3 and DG. These results indicate that AMPA receptor signals are part of cellular repair responses following exposure to an environmental toxin. In the experiment, the researchers used many compounds, for example, Piperidin-1-yl(quinoxalin-6-yl)methanone (cas: 154235-83-3Category: quinoxaline).

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider

Patel, Nandini C. et al. published their research in Journal of Medicinal Chemistry in 2013 | CAS: 154235-83-3

Discovery and Characterization of a Novel Dihydroisoxazole Class of α-Amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) Receptor Potentiators was written by Patel, Nandini C.;Schwarz, Jacob;Hou, Xinjun J.;Hoover, Dennis J.;Xie, Longfei;Fliri, Anton J.;Gallaschun, Randall J.;Lazzaro, John T.;Bryce, Dianne K.;Hoffmann, William E.;Hanks, Ashley N.;McGinnis, Dina;Marr, Eric S.;Gazard, Justin L.;Hajos, Mihaly;Scialis, Renato J.;Hurst, Raymond S.;Shaffer, Christopher L.;Pandit, Jayvardhan;O’Donnell, Christopher J.. And the article was included in Journal of Medicinal Chemistry in 2013.Formula: C14H15N3O This article mentions the following:

Pos. allosteric modulators (“potentiators”) of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors (AMPAR) enhance excitatory neurotransmission and may improve the cognitive deficits associated with various neurol. disorders. The dihydroisoxazole (DHI) series of AMPAR potentiators described herein originated from the identification of one compound by a high-throughput functional activity screen using mouse embryonic stem (mES) cell-derived neuronal precursors. Subsequent structure-based drug design using X-ray crystal structures of the ligand-binding domain of human GluA2 led to the discovery of both PF-04725379, which in tritiated form became a novel ligand for characterizing the binding affinities of subsequent AMPAR potentiators in rat brain homogenate, and PF-04701475 , a prototype used to explore AMPAR-mediated pharmacol. in vivo. Lead series optimization provided a functionally potent compound lacking the potentially bioactivatable aniline within another compound, but retaining desirable in vitro ADME properties. In the experiment, the researchers used many compounds, for example, Piperidin-1-yl(quinoxalin-6-yl)methanone (cas: 154235-83-3Formula: C14H15N3O).

Referemce:
Quinoxaline – Wikipedia,
Quinoxaline | C8H6N2 | ChemSpider