Heterocyclic Building Blocks-quinoxaline

Liu, Chong published the artcileCaSR activates PKCδ to induce cardiomyocyte apoptosis via ER stress associated apoptotic pathways during ischemia/reperfusion, Application In Synthesis of 226878-01-9, the publication is International Journal of Molecular Medicine (2019), 44(3), 1117-1126, database is CAplus and MEDLINE.

Endoplasmic reticulum (ER) stress can be activated by ischemia/reperfusion (I/R) injury in cardiomyocytes. Persistent ER stress, with an increase in intracellular Ca²⁺ ([Ca²⁺]i) concentration, leads to apoptosis. Protein kinase C (PKC) has a key role in myocardial damage by elevation of [Ca²⁺]i. The calcium-sensing receptor (CaSR), a G protein-coupled receptor, can increase the release of [Ca²⁺]i from the ER through the inositol triphosphate receptor (IP₃R). Intracellular calcium overload has been demonstrated to cause cardiac myocyte apoptosis during I/R. However, the associations between PKC, CaSR and ER stress are not clear. The present study examined the hypothesis that activation of PKCδ by CaSR participates in ER stress-associated apoptotic pathways within myocardial I/R. Rat hearts were subjected to 30 min of ischemia in vivo, followed by reperfusion for 120 min. GdCl₃ (a CaSR activator) was used to elevate the intracellular Ca²⁺ concentration, but the Ca²⁺ concentration in the ER was significantly decreased during I/R. Following exposure to GdCl₃, expression levels of CaSR, glucose-regulated protein 78 (GRP78), Caspase-12, phosphorylated JNK and Caspase-3 were increased, and the ratios of apoptotic myocardial cells were significantly increased. By contrast, following exposure to rottlerin, a PKCδ inhibitor, the expression levels of these proteins and the ratio of apoptotic myocardial cells were significantly reduced. The present study also demonstrated that PKCd translocated into the ER to induce an ER stress response and participate in the ER stress-related apoptosis pathway. These results confirmed that CaSR activated PKCδ to induce cardiomyocyte apoptosis through ER stress-associated apoptotic pathways during I/R in vivo.

International Journal of Molecular Medicine 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 C19H21N3O, Application In Synthesis of 226878-01-9.

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

Hernandez Zenteno, Rafael J. published the artcileVarenicline for long term smoking cessation in patients with COPD, COA of Formula: C17H19N3O6, the publication is Pulmonary Pharmacology & Therapeutics (2018), 116-120, database is CAplus and MEDLINE.

Quitting smoking is key for patients with Chronic Obstructive Pulmonary Disease (COPD). Standard recommendations for quitting smoking are implemented for COPD as well. Varenicline Tartrate (VT) is the most effective drug to help quit smoking, but few studies have analyzed its effectiveness. Aim of the study: To determine the Abstinence Rate (AR) at 12 mo, in COPD and non-COPD smokers. Observational study in 31 COPD (post bronchodilator-BD FEV₁/FVC <0.70) and in 63 non-COPD smokers, were invited to receive treatment with Varenicline Tartrate (VT). Fourteen subjects with COPD and 46 non-COPD subjects received addnl. Cognitive-Behavioral Therapy (CBT). Abstinence rate (AR) was validated by exhaled carbon monoxide CO (COe), in addition to a phone or face-to-face interview. Motivation score was measured with a visual analog scale (MS). Differences between COPD and non-COPD, mean FEV₁/FVC ratio 0.52 ± 0.10 vs. 0.90 ± 0.15, age 60 ± 10 vs. 47 ± 10 years, smoking pack-years 37 ± 3.5 vs. 22 ± 12, and COe 16 ± 11 vs. 12 ± 9 ppm were statistically significant (p < 0.05); for MS the score was 93 ± 11 vs. 93 ± 11 and for attempts to quit (AQ) 2 ± 2 vs. 2 ± 3 were not. AR was not significantly different at 12 mo (61.2 vs. 42.8% p = 0.072). Motivation was the only significant one-year AR predictor. COPD smokers had a similar response (higher tendency) to VT regardless of the presence of airflow obstruction and stronger nicotine addiction.

Pulmonary Pharmacology & Therapeutics 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

Satheesh, B. published the artcileUPLC separation and quantification of related substances of varenicline tartrate tablet, SDS of cas: 375815-87-5, the publication is Acta Chromatographica (2010), 22(2), 207-218, database is CAplus.

A new ultra-performance liquid chromatog. (UPLC) method was developed and validated for quantification of substances related to varenicline tartrate, process-related and degradation products, in pharmaceutical formulations. Chromatog. separation of 6 impurities was performed on a reversed phase column. The method was validated for linearity, limits of detection and quantification, accuracy, precision, and selectivity. The calibration plots obtained for the 6 impurities were linear over the range 0.005-0.30%. The relative standard deviations (s_r) of intra and inter-day experiments were < 1.0%. The detection limits ranged between 0.002 and 0.004%, depending on the impurity. The proposed UPLC method was successfully applied to quantification of varenicline impurities in its pharmaceutical formulation.

Acta Chromatographica 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, SDS of cas: 375815-87-5.

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

Waeiss, Robert A. published the artcileTherapeutic challenges for concurrent ethanol and nicotine consumption: naltrexone and varenicline fail to alter simultaneous ethanol and nicotine intake by female alcohol-preferring (P) rats, Quality Control of 375815-87-5, the publication is Psychopharmacology (Heidelberg, Germany) (2019), 236(6), 1887-1900, database is CAplus and MEDLINE.

Rationale and objectives: Simultaneous alc. and nicotine consumption occurs in the majority of individuals with alc. use disorder (AUD) and nicotine dependence. Varenicline (Var) is used to assist in the cessation of nicotine use, while naltrexone (Nal) is the standard treatment for AUD. Despite evidence that ethanol (EtOH) and nicotine (NIC) co-use produces unique neuroadaptations, preclin. research has focused on the effects of pharmacotherapeutics on a single reinforcer. The current experiments examined the effects of Var and Nal on EtOH, NIC, or EtOH+NIC intake. Methods: Animals were randomly assigned to one of four drinking conditions of 24-h access to a three-bottle choice paradigm, one of which always contained water. Drinking conditions were water only, 0.07 and 0.14 mg/mL NIC (NIC only), 15% and 30% EtOH (EtOH only), or 15% and 30% EtOH with 0.14 mg/mL NIC (EtOH+NIC). Results: Var reduced maintenance and relapse NIC intake but had no effect on EtOH or EtOH+NIC drinking. Conversely, Nal reduced EtOH maintenance and relapse drinking, but had no effect on NIC or EtOH+NIC drinking. Discussion: The results indicate the standard pharmacol. treatments for nicotine dependence and AUD were effective at reducing consumption of the targeted reinforcer but neither reduced EtOH+NIC co-use/abuse. These findings suggest that co-abuse may promote unique neuroadaptations that require models of polysubstance abuse to develop pharmacotherapeutics to treat AUD and nicotine dependence.

Psychopharmacology (Heidelberg, Germany) 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 C20H19NO4, Quality Control of 375815-87-5.

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

Park, Jin-Woo published the artcilePharmacokinetic comparisons of two different varenicline formulations in humans: Varenicline tartrate versus varenicline oxalate, COA of Formula: C17H19N3O6, the publication is International Journal of Clinical Pharmacology and Therapeutics (2020), 58(2), 121-127, database is CAplus and MEDLINE.

Varenicline is an effective drug for smoking cessation. The aim of the present study was to compare the pharmacokinetics and safety profies of two different varenicline formulations (varenicline tartrate (reference) and varenicline oxalate (test)), each containing 1 mg varenicline base in humans. A randomized, open-label, two-sequence, two-period, single-dose crossover study with a 2-wk washout period was conducted with 30 healthy male participants. Blood samples for the pharmacokinetic anal. of varenicline were collected up to 96 h following the administration of each drug. Pharmacokinetic parameters were also calculated, including the peak plasma concentration (C_max), area under the plasma concentration-time curve (AUC) from time zero to the time of the last measurable concentration (AUC_last) as well as AUC from time zero to infiity (AUC_inf). ANOVA for pharmacokinetic equivalence was assessed using log-transformed C_max and AUC values, and the geometric mean ratios (GMRs) and their 90% confience intervals (CIs) were assessed as well. The safety profies were also assessed. 27 participants completed the study. No signifiant differences were found for any pharmacokinetic parameters of varenicline between the two formulations. The observed average values of C_max, AUC_last, and AUC_inf were 4.46 ng/mL, 97.68 ngxh/mL, and 101.60 ngxh/mL for reference and 4.54 ng/mL, 97.10 ngxh/mL, and 100.97 ngxh/mL for test, resp. The GMRs and 90% CIs for C_max, AUC_last, and AUC_inf were 1.0106 (0.9626 – 1.0610), 0.9904 (0.9540 – 1.0282), and 0.9885 (0.9517 – 1.0268), resp. No clin. relevant changes were observed in the phys., biochem., hematol., electrocardiog., or urinalysis fidings during the study, and no serious adverse events were found. The results of the present study reveal that varenicline oxalate and varenicline tartrate have similar pharmacokinetic characteristics as varenicline, and that these two formulations exhibit pharmacokinetic equivalence to meet the regulatory criteria. Both varenicline formulations were generally well tolerated.

International Journal of Clinical Pharmacology and Therapeutics 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

Pujeri, Sudhakar S. published the artcileStress degradation studies on varenicline tartrate and development of a validated stability-indicating HPLC method, COA of Formula: C17H19N3O6, the publication is Scientia Pharmaceutica (2012), 80(1), 115-126, database is CAplus and MEDLINE.

A simple, rapid, and stability-indicating reversed-phase liquid chromatog. method was developed for the assay of varenicline tartrate (VRT) in the presence of its degradation products generated from forced decomposition studies. The HPLC separation was achieved on a C₁₈ Inertsil column (250 mm × 4.6 mm i.d. particle size is 5 μm) employing a mobile phase consisting of ammonium acetate buffer containing trifluoroacetic acid (0.02 M; pH 4) and acetonitrile in gradient program mode with a flow rate of 1.0 mL/min^-1. The UV detector was operated at 237 nm while column temperature was maintained at 40°. The developed method was validated as per ICH guidelines with respect to specificity, linearity, precision, accuracy, robustness, and limit of quantification. The method was found to be simple, specific, precise, and accurate. Selectivity of the proposed method was validated by subjecting the stock solution of VRT to acidic, basic, photolysis, oxidative, and thermal degradation The calibration curve was found to be linear in the concentration range of 0.1-192 μg/mL^-1 (R² = 0.9994). The peaks of degradation products did not interfere with that of pure VRT. The utility of the developed method was examined by analyzing the tablets containing VRT. The results of anal. were subjected to statistical anal.

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, COA of Formula: C17H19N3O6.

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

Goura, Ramesh published the artcileImproved and ′Nitrosamines Free′ Process for the Preparation of an α4β2 Neuronal Nicotinic Acetylcholine Receptor Agonist-Varenicline Tartrate, HPLC of Formula: 375815-87-5, the publication is Polycyclic Aromatic Compounds, database is CAplus.

An improvised and efficient approach for synthesis of α4β2 nicotinic acetylcholine receptor subtype agonist, Varenicline tartrate free from the ′N-nitrosamines′ has been described. The approach involves an improved process for a key intermediate (7,8-dinitro-4,5-dihydro-1H-1,5-methanobenzo[d] azepin-3(2H)-yl)-2,2,2-trifluoro ethanone free from potential genotoxic impurities. Compound is converted into Varenicline base in a single pot process with improved overall yield and quality. Further, Varenicline base is converted into Varenicline tartrate by acid addition salt which provides in quant. yield. This improved process consists of tech. innovations/improvements which eliminate the probability for the formation of critical impurities such as dinitro nitroso impurity , diamino nitroso impurity and varenicline nitroso impurity and other genotoxic impurities such as mono nitro impurity and meta dinitro impurity in the final drug substance and provides ′Nitrosamines free′ varenicline tartrate with good quality and yield.

Polycyclic Aromatic Compounds 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, HPLC of Formula: 375815-87-5.

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

Poornesh, Gowda A. S. published the artcileDevelopment and validation of analytical method for simultaneous estimation of varenicline tartrate and bupropion hydrochloride, Recommanded Product: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, the publication is World Journal of Pharmacy and Pharmaceutical Sciences (2019), 8(2), 925-937, database is CAplus.

A simple, sensitive, precise, rapid and accurate reverse phase high performance liquid chromatog. (RP-HPLC) method was developed and validated for simultaneous estimation of Varenicline tartrate and Bupropion hydrochloride. The Chromatog. separation was achieved by using Cosmosil C18 (250 mm × 4.6 mm, 5μ) as stationary phase and mobile phase consists of Methanol: phosphate buffer with pH 3.0 (65:35 volume/volume) with a flow rate of 1ml/min. The anal. was performed at ambient temperature and the eluent was monitored at 244 nm using UV detector. The retention time of Varenicline tartrate and Bupropion hydrochloride was found to be 3.0 min and 4.2 min resp. and the calibration curves were linear (r2 = 0.999 and 0.998) over a concentration range of 10-50μg/mL for Varenicline tartrate and 100-500μg/mL for Bupropion hydrochloride resp. The Limit of detection (LOD) for Varenicline tartrate and Bupropion hydrochloride was observed to be 0.002μg/mL and 0.006μg/mL resp., the limit of quantitation (LOQ) was found to be 0.006μg/mL and 0.018μg/mL resp. The developed method was validated as per ICH guidelines using parameters like linearity, specificity, system suitability, precision, ruggedness, robustness, accuracy. All the validation parameters were found to be well within the acceptance criteria. Hence the proposed method can be used for the routine anal. of Varenicline tartrate and Bupropion hydrochloride in bulk and tablet dosage forms.

World Journal of Pharmacy and Pharmaceutical Sciences 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, Recommanded Product: 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

Vanejevs, Maksims published the artcilePositive and Negative Modulation of Group I Metabotropic Glutamate Receptors, Application In Synthesis of 226878-01-9, the publication is Journal of Medicinal Chemistry (2008), 51(3), 634-647, database is CAplus and MEDLINE.

A discriminating pharmacophore model for noncompetitive metabotropic glutamate receptor antagonists of subtype 1 (mGluR1) was developed that facilitated the discovery of moderately active mGluR1 antagonists. One scaffold was selected for the design of several focused libraries where different substitution patterns were introduced. This approach facilitated the discovery of potent mGluR1 antagonists, as well as pos. and neg. mGluR5 modulators, because both receptor subtypes share similar binding pockets. For mGluR1 antagonists, a homol. model of the mGlu1 receptor was established, and a putative binding mode within the receptor’s transmembrane domain was visualized.

Journal of Medicinal Chemistry 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 C9H5ClO4S, Application In Synthesis of 226878-01-9.

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

Lavreysen, Hilde published the artcile[³H]R214127: A novel high-affinity radioligand for the mGlu1 receptor reveals a common binding site shared by multiple allosteric antagonists, SDS of cas: 226878-01-9, the publication is Molecular Pharmacology (2003), 63(5), 1082-1093, database is CAplus and MEDLINE.

R214127 was shown to be a potent and noncompetitive metabotropic glutamate 1 (mGlu1) receptor-selective antagonist. The kinetics and pharmacol. of [³H]1-(3,4-dihydro-2H-pyrano[2,3-b]quinolin-7-yl)-2-phenyl-1- ethanone (R214127) binding to rat mGlu1a receptor Chinese hamster ovary (CHO)-dhfr^– membranes was investigated, as well as the distribution of [³H]R214127 binding in rat brain tissue and sections. Specific binding to rat mGlu1a receptor CHO-dhfr^– membranes was ∼92% of total and was optimal at 4°. Full association was reached within 5 min, and [³H]R214127 bound to a single binding site with an apparent K_D of 0.90 nM and a B_max of 6512 fmol/mg of protein. Inhibition experiments showed that [³H]R214127 binding was completely blocked by 2-quinoxaline-carboxamide-N-adamantan-1-yl (NPS 2390), (3aS,6aS)-6a-naphtalan-2-ylmethyl-5-methyliden-hexahydro-cyclopenta[c] furan-1-on (BAY 36-7620), and 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate Et ester (CPCCOEt), but was not displaced by competitive mGlu1 receptor ligands such as glutamate and quisqualate, suggesting that R214127, NPS 2390, BAY 36-7620, and CPCCOEt bind to the same site or mutually exclusive sites. Experiments using rat cortex, striatum, hippocampus and cerebellum revealed that [³H]R214127 labeled a single high-affinity binding site (K_D ∼ 1 nM). B_max values were highest in the cerebellum (4302 fmol/mg of protein) and were 741, 688, and 471 fmol/mg of protein in the striatum, hippocampus, and cortex, resp. The distribution of [³H]R214127 binding in rat brain was investigated in more detail by radioligand autoradiog. A high d. of binding sites was detected in the mol. layer of the cerebellum. Moderate labeling was seen in the CA3 and dentate gyrus of the hippocampus, thalamus, olfactory tubercle, amygdala, and substantia nigra reticulata. The cerebral cortex, caudate putamen, ventral pallidum, and nucleus accumbens showed lower labeling. The high affinity and selectivity of [³H]R214127 for mGlu1 receptors renders this compound the ligand of choice to study the native mGlu1 receptor in brain.

Molecular Pharmacology 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 C19H21N3O, SDS of cas: 226878-01-9.

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