Category: quinoxaline

Xue, Zhaoliang published the artcileCalcium-sensing receptor antagonist NPS2390 attenuates neuronal apoptosis though intrinsic pathway following traumatic brain injury in rats, SDS of cas: 226878-01-9, the publication is Biochemical and Biophysical Research Communications (2017), 486(2), 589-594, database is CAplus and MEDLINE.

Traumatic brain injury (TBI) initiates a complex cascade of neurochem. and signaling changes that leads to neuronal apoptosis, which contributes to poor outcomes for patients with TBI. Previous study indicates that calcium-sensing receptor (CaSR) activation contributes to neuron death in focal cerebral ischemia-reperfusion mice, however, its role in neuronal apoptosis after TBI is not well-established. Using a controlled cortical impact model in rats, the present study was designed to determine the effect of CaSR inhibitor NPS2390 upon neuronal apoptosis after TBI. Rats were randomly distributed into three groups undergoing the sham surgery or TBI procedure, and NPS2390 (1.5 mg/kg) was infused s.c. at 30 min and 120 min after TBI. All rats were sacrificed at 24 h after TBI. Our data indicated that NPS2390 significantly reduced the brain edema and improved the neurol. function after TBI. In addition, NPS2390 decreased caspase-3 levels and the number of apoptotic neurons. Furthermore, NPS2390 up-regulated anti-apoptotic protein Bcl-2 expression and down-regulated pro-apoptotic protein Bax, and reduced subsequent release of cytochrome c into the cytosol. In summary, this study indicated that inhibition of CaSR by NPS2390 attenuates neuronal apoptosis after TBI, in part, through modulating intrinsic apoptotic pathway.

Biochemical and Biophysical Research Communications published new progress about 226878-01-9. 226878-01-9 belongs to quinoxaline, auxiliary class Neuronal Signaling,mGluR, name is N-(Adamantan-1-yl)quinoxaline-2-carboxamide, and the molecular formula is C15H14O, SDS of cas: 226878-01-9.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Wildeboer-Andrud, Kristin M. published the artcileThe smoking cessation drug varenicline improves deficient P20-N40 inhibition in DBA/2 mice, Related Products of quinoxaline, the publication is Pharmacology, Biochemistry and Behavior (2011), 100(1), 17-24, database is CAplus and MEDLINE.

Varenicline, an FDA approved smoking cessation pharmacotherapy, is an α4β2* nicotinic acetylcholine receptor (nAChR) partial agonist and an α7* nAChR full agonist. Both subtypes of nAChR are involved in modulating auditory evoked responses in rodents. In DBA/2 mice, an inbred strain, auditory evoked responses to paired auditory stimuli fail to inhibit to the second stimulus. This mouse strain replicates the auditory evoked response inhibition deficit experienced by the majority of schizophrenia patients. In this current study, we examined the effects of five different doses of varenicline (0.06, 0.3, 0.6, 3 and 6 mg/kg) on auditory evoked responses in anesthetized DBA/2 mice. We also administered α4β2* and α7* nAChR selective antagonists prior to varenicline administration to determine which nAChR subtypes mediate the effects of varenicline. Four of the five doses of varenicline produced improvements in auditory evoked response inhibition deficits. Selective blockade of either the α4β2* or α7* nAChR in competition with 0.6 mg/kg varenicline prevented varenicline induced improvements. In competition with a higher dose of varenicline (3 mg/kg) only blockade of the α4β2* nAChR prevented varenicline induced improvement in auditory evoked response inhibition. These data indicate the importance of α4β2* nAChRs and the potential involvement of the α7* subtype in varenicline’s effects on auditory evoked responses in DBA/2 mice.

Pharmacology, Biochemistry and Behavior published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C7H16Cl2Si, Related Products of quinoxaline.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Ding, Li published the artcileSmoking-cessation drugs and the related technological progress, Quality Control of 375815-87-5, the publication is Shanghai Yiyao (2007), 28(4), 170-172, database is CAplus.

A review. At present, smoking has been a serious social problem. Smoking-cessation drugs and the related technol. are developing in a variety of directions. The development of nicotine replacement therapy and technol., chem. drugs (amfebutamone hydrochloride, varenicline tartrate and rimonabant), vaccine, tradition Chinese medicines, and acupuncture therapy are reviewed with 3 references

Shanghai Yiyao published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C17H19N3O6, Quality Control of 375815-87-5.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Lu, Yuting published the artcileImpurity profiling of varenicline tartrate by LC-QTOF mass spectrometric techniques during drug development, Product Details of C17H19N3O6, the publication is Journal of Pharmaceutical and Biomedical Analysis (2018), 306-313, database is CAplus and MEDLINE.

HPLC-QTOF-MS method was developed for the separation and characterization of related substances in varenicline tartrate drug material. The separation used InertSustain C18 column (4.6 × 150 mm, 5 μm) with liner gradient elution using 0.05% trifluoroacetic acid as mobile phase A and acetonitrile as mobile phase B. The degradation studies were conducted under the ICH prescribed stress conditions. Varenicline tartrate was unstable to alk., oxidative, thermal and photolytic stresses, but relatively stable under acid stress condition. Thirteen related substances were found in varenicline tartrate and its stressed samples. Their structures were identified mainly through pos. ESI high resolution QTOF mass spectrometric anal. of the parent and product ion accurate masses and the calculated elemental compositions Among the 13 substances, 7 were process-related and 6 were degradation products, and two of them were further verified by chem. synthesis and NMR spectroscopic determination Their formation mechanisms are discussed, and the key steps in the manufacturing processes are determined to provide varenicline tartrate with high purity.

Journal of Pharmaceutical and Biomedical Analysis published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C17H19N3O6, Product Details of C17H19N3O6.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Hong, L. Elliot published the artcileEffects of moderate-dose treatment with varenicline on neurobiological and cognitive biomarkers in smokers and nonsmokers with schizophrenia or schizoaffective disorder, Application In Synthesis of 375815-87-5, the publication is Archives of General Psychiatry (2011), 68(12), 1195-1206, database is CAplus and MEDLINE.

The administration of nicotine transiently improves many neurobiol. and cognitive functions in schizophrenia and schizoaffective disorder. It is not yet clear which nicotinic acetylcholine receptor (nAChR) subtype or subtypes are responsible for these seemingly pervasive nicotinic effects in schizophrenia and schizoaffective disorder. Because α4β2 is a key nAChR subtype for nicotinic actions, we investigated the effect of varenicline tartrate, a relatively specific α4β2 partial agonist and antagonist, on key biomarkers that are associated with schizophrenia and are previously shown to be responsive to nicotinic challenge in humans. A double-blind, parallel, randomized, placebo-controlled trial of patients with schizophrenia or schizoaffective disorder was conducted to examine the effects of varenicline on biomarkers at 2 wk (short-term treatment) and 8 wk (long-term treatment), using a slow titration and moderate dosing strategy for retaining α4β2-specific effects while minimizing adverse effects. Participants included a total of 69 smoking and nonsmoking patients; 64 patients completed week 2, and 59 patients completed week 8. Main outcome measures were prepulse inhibition, sensory gating, antisaccade, spatial working memory, eye tracking, processing speed, and sustained attention. Results: A moderate dose of varenicline (1) significantly reduced the P50 sensory gating deficit in nonsmokers after long-term treatment (P=.006), (2) reduced startle reactivity (P=.02) regardless of baseline smoking status, and (3) improved executive function by reducing the antisaccadic error rate (P=.03) regardless of smoking status. A moderate dose of varenicline had no significant effect on spatial working memory, predictive and maintenance pursuit measures, processing speed, or sustained attention by Conners’ Continuous Performance Test. Clin., there was no evidence of exacerbation of psychiatric symptoms, psychosis, depression, or suicidality using a gradual titration (1-mg daily dose). Moderate-dose treatment with varenicline has a unique treatment profile on core schizophrenia-related biomarkers. Further development is warranted for specific nAChR compounds and dosing and duration strategies to target subgroups of schizophrenic patients with specific biol. deficits. Trial Registration: clinicaltrials.gov Identifier: NCT00492349.

Archives of General Psychiatry published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C17H19N3O6, Application In Synthesis of 375815-87-5.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Yanamala, Naveena published the artcilePreferential binding of allosteric modulators to active and inactive conformational states of metabotropic glutamate receptors, Category: quinoxaline, the publication is BMC Bioinformatics (2008), No pp. given, database is CAplus and MEDLINE.

Metabotropic glutamate receptors (mGluRs) are G protein coupled receptors that play important roles in synaptic plasticity and other neuro-physiol. and pathol. processes. Allosteric mGluR ligands are particularly promising drug targets because of their modulatory effects – enhancing or suppressing the response of mGluRs to glutamate. The mechanism by which this modulation occurs is not known. Here, the authors propose the hypothesis that pos. and neg. modulators will differentially stabilize the active and inactive conformations of the receptors, resp. To test this hypothesis, the authors have generated computational models of the transmembrane regions of different mGluR subtypes in two different conformations. The inactive conformation was modeled using the crystal structure of the inactive, dark state of rhodopsin as template and the active conformation was created based on a recent model of the light-activated state of rhodopsin. Ligands for which the nature of their allosteric effects on mGluRs is exptl. known were docked to the modeled mGluR structures using ArgusLab and Autodock softwares. The authors find that the allosteric ligand binding pockets of mGluRs are overlapping with the retinal binding pocket of rhodopsin, and that ligands have strong preferences for the active and inactive states depending on their modulatory nature. In 8 out of 14 cases (57%), the neg. modulators bound the inactive conformations with significant preference using both docking programs, and 6 out of 9 cases (67%), the pos. modulators bound the active conformations. Considering results by the individual programs only, even higher correlations were observed: 12/14 (86%) and 8/9 (89%) for ArgusLab and 10/14 (71%) and 7/9 (78%) for AutoDock. These findings strongly support the hypothesis that mGluR allosteric modulation occurs via stabilization of different conformations analogous to those identified in rhodopsin where they are induced by photochem. isomerization of the retinal ligand – despite the extensive differences in sequences between mGluRs and rhodopsin.

BMC Bioinformatics published new progress about 226878-01-9. 226878-01-9 belongs to quinoxaline, auxiliary class Neuronal Signaling,mGluR, name is N-(Adamantan-1-yl)quinoxaline-2-carboxamide, and the molecular formula is C38H74Cl2N2O4, Category: quinoxaline.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Cousin, Margot A. published the artcileLarval zebrafish model for FDA-approved drug repositioning for tobacco dependence treatment, Application of 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, the publication is PLoS One (2014), 9(3), e90467/1-e90467/10, 10 pp., database is CAplus and MEDLINE.

Cigarette smoking remains the most preventable cause of death and excess health care costs in the United States, and is a leading cause of death among alcoholics. Long-term tobacco abstinence rates are low, and pharmacotherapeutic options are limited. Repositioning medications approved by the U.S. Food and Drug Administration (FDA) may efficiently provide clinicians with new treatment options. We developed a drug-repositioning paradigm using larval zebrafish locomotion and established predictive clin. validity using FDA-approved smoking cessation therapeutics. We evaluated 39 physician-vetted medications for nicotine-induced locomotor activation blockade. We further evaluated candidate medications for altered ethanol response, as well as in combination with varenicline for nicotine-response attenuation. Six medications specifically inhibited the nicotine response. Among this set, apomorphine and topiramate blocked both nicotine and ethanol responses. Both pos. interact with varenicline in the Bliss Independence test, indicating potential synergistic interactions suggesting these are candidates for translation into Phase II clin. trials for smoking cessation.

PLoS One published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C17H19N3O6, Application of 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Satheesh, Balasubramanian published the artcileIdentification, isolation and characterization of an unknown impurity of varenicline, Application In Synthesis of 375815-87-5, the publication is Scientia Pharmaceutica (2012), 80(2), 329-336, database is CAplus and MEDLINE.

An unknown impurity formed during stability sample anal. by a gradient reversed phase ultra-high pressure liquid chromatog. (UHPLC) of varenicline tablets at 0.2% level. A simple isocratic preparative method was developed to isolate the unknown impurity with 20 min run time. This unknown impurity was identified and characterized by spectroscopic techniques. Based on the spectral data, the unknown impurity was characterized as 4,6,7,8,9,10-hexahydro-1H-6,10-methanopyrazino[2,3-h][3]benzazepine-2,3-dione. The structure of this impurity was also established unambiguously, prepared by isolation and co-injected into UHPLC to confirm the retention time. To the best of the authors’ knowledge, this impurity was not reported elsewhere.

Scientia Pharmaceutica published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C17H19N3O6, Application In Synthesis of 375815-87-5.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Kaduk, James A. published the artcilePowder X-ray diffraction of varenicline hydrogen tartrate Form B (Chantix⁾, (C₁₃H₁₄N₃)(HC₄H₄O₆), COA of Formula: C17H19N3O6, the publication is Powder Diffraction (2021), 36(3), 202-204, database is CAplus.

The crystal structure of varenicline hydrogen tartrate Form B (Chantix) has been refined using synchrotron X-ray powder diffraction data and optimized using d. functional techniques. Varenicline hydrogen tartrate Form B crystallizes in space group P2₁2₁2₁ (#19) with a = 7.07616(2), b = 7.78357(2), c = 29.86149(7) Å, V = 1644.706(6) ų, and Z = 4. The hydrogen bonds were identified and quantified. Hydrogen bonds link the cations and anions in zig-zag chains along the b-axis. The powder pattern has been submitted to ICDD for inclusion in the Powder Diffraction File (PDF).

Powder Diffraction published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C17H19N3O6, COA of Formula: C17H19N3O6.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider

Oncken, Cheryl published the artcileEfficacy and safety of the novel selective nicotinic acetylcholine receptor partial agonist, varenicline, for smoking cessation, Application In Synthesis of 375815-87-5, the publication is Archives of Internal Medicine (2006), 166(15), 1571-1577, database is CAplus and MEDLINE.

The selective nicotinic acetylcholine receptor partial agonist, varenicline tartrate, represents a novel type of therapy for smoking cessation. This study evaluated the efficacy, safety, and tolerability of 4 varenicline dose regimens, 2 with progressive dosing over the first week (eg, titrated) and 2 with a fixed dosing schedule (eg, non-titrated), for promoting smoking cessation. This multicenter, double-blind, placebo-controlled study randomized healthy smokers (aged 18-65 years) to varenicline tartrate, 0.5 mg twice daily nontitrated (n = 129), 0.5 mg twice daily titrated (n = 130), 1.0 mg twice daily nontitrated (n = 129), 1.0 mg twice daily titrated (n = 130), or placebo (n = 129) for 12 wk to aid in smoking cessation. A 40-wk follow-up period assessed long-term efficacy. The primary efficacy measures were the carbon monoxide-confirmed 4-wk continuous quit rates by pooled dosage group for weeks 4 through 7 and 9 through 12 and the continuous abstinence rates for weeks 9 through 52. Weeks 9 through 12 continuous quit rates were greater in the 1.0-mg group (49.4%) and the 0.5-mg group (44.0%) vs placebo (11.6%; P < .001 vs both doses). Weeks 9 through 52 abstinence rates were greater in the 1.0-mg group (22.4%; P < .001) and the 0.5-mg group (18.5%; P < .001) vs placebo (3.9%). Varenicline was generally well tolerated, with nausea occurring in 16% to 42% of varenicline-treated subjects. Reports of nausea were lower for the titrated vs nontitrated dosing and infrequently led to medication discontinuation. Varenicline tartrate, 0.5 mg and 1.0 mg twice daily, is efficacious for smoking cessation.

Archives of Internal Medicine published new progress about 375815-87-5. 375815-87-5 belongs to quinoxaline, auxiliary class Neuronal Signaling,AChR,Natural product, name is 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, and the molecular formula is C17H19N3O6, Application In Synthesis of 375815-87-5.

Referemce:
https://en.wikipedia.org/wiki/Quinoxaline,
Quinoxaline | C8H6N2 | ChemSpider