Heterocyclic Building Blocks-quinoxaline

Sajja, Ravi K. published the artcileNicotinic receptor partial agonists modulate alcohol deprivation effect in C57BL/6J mice, Recommanded Product: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, the publication is Pharmacology, Biochemistry and Behavior (2013), 161-167, database is CAplus and MEDLINE.

Relapse is a core feature of alc. addiction and hinders the pharmacotherapy of alc. use disorders. Pre-clin. and clin. studies have shown that neuronal nicotinic acetylcholine receptor (nAChR) partial agonists such as cytisine and its derivative, varenicline, reduce alc. (ethanol) consumption and seeking behavior. However, the effects of these ligands on ethanol relapse are little understood. In the present study, we examined the effects of varenicline and cytisine on alc. deprivation effect (ADE) – a validated model for relapse-like ethanol drinking in C57BL/6J mice. After habituation to 15% (volume/volume) ethanol intake using a continuous free-choice procedure, mice were exposed to alternating cycles of ethanol deprivation (5 days) and re-exposure (2 days). At the end of third deprivation cycle, animals received repeated i.p. injections of saline, varenicline (0.5 or 3.0 mg/kg) or cytisine (0.5 or 3.0 mg/kg) and fluid intake was measured post 4 h and 24 h ethanol re-exposure. Repeated ethanol deprivation and re-exposure cycles significantly produced a robust and transient increase in ethanol (ADE). Pretreatment with varenicline (0.5 or 3.0 mg/kg) or cytisine (0.5 or 3.0 mg/kg) significantly reduced the expression of ADE at 4 h and 24 h after ethanol re-exposure. The results from this study indicate that nAChR partial agonists reduce the expression of ADE in mice and further suggest the involvement of nAChR mechanisms in ADE, a relapse-like ethanol drinking behavior.

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 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

Lavreysen, Hilde published the artcileMetabotropic glutamate 1 receptor distribution and occupancy in the rat brain: a quantitative autoradiographic study using [³H]R214127, Application of N-(Adamantan-1-yl)quinoxaline-2-carboxamide, the publication is Neuropharmacology (2004), 46(5), 609-619, database is CAplus and MEDLINE.

We used the selective metabotropic glutamate (mGlu) 1 receptor antagonist [³H]1-(3,4-dihydro-2H-pyrano[2,3-b]quinolin-7-yl)-2-phenyl-1-ethanone ([³H]R214127) to investigate the distribution of mGlu1 receptor binding sites in rat brain. We found high mGlu1 receptor binding in the cerebellum, thalamus, dentate gyrus and medial central gray, moderate binding within the CA3 of the hippocampus and hypothalamus, and low mGlu1 receptor binding in the basal ganglia and cortex. The mGlu1 receptor is also present in variable degree in the dorsal lateral septal nucleus, amygdala, interpeduncular nucleus and median raphe nucleus. Addnl., we employed [³H]R214127 autoradiog. as a means of investigating the occupancy of central mGlu1 receptors following in vivo administration of mGlu1 receptor antagonists that prevent binding of this radioligand. We found that the mGlu1 receptor antagonist (3aS,6aS)-6a-naphtalan-2-ylmethyl-5-methyliden-hexahydro-cyclopenta[c]furan-1-on (BAY 36-7620), administered s.c. at 10 mg/kg, only occupied about 30% of cerebellar and thalamic mGlu1 receptors. The mGlu1/5 receptor antagonist 2-quinoxaline-carboxamide-N-adamantan-1-yl (NPS 2390) exhibited a relatively high potency in occupying mGlu1 receptors in rat cerebellum (ED₅₀ = 0.75 mg/kg, s.c.) and thalamus (ED₅₀ = 0.63 mg/kg, s.c). In the future, this method can be employed to gain more insight into the in vivo profile and central activity of potential therapeutic agents that act upon the mGlu1 receptor.

Neuropharmacology 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 of N-(Adamantan-1-yl)quinoxaline-2-carboxamide.

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

Dave, Rutwij A. published the artcileNovel high/low solubility classification methods for new molecular entities, COA of Formula: C17H19N3O6, the publication is International Journal of Pharmaceutics (Amsterdam, Netherlands) (2016), 511(1), 111-126, database is CAplus and MEDLINE.

This research describes a rapid solubility classification approach that could be used in the discovery and development of new mol. entities. Compounds (N = 635) were divided into two groups based on information available in the literature: high solubility (BDDCS/BCS 1/3) and low solubility (BDDCS/BCS 2/4). We established decision rules for determining solubility classes using measured log solubility in molar units (MLogS_M) or measured solubility (MSol) in mg/mL units. ROC curve anal. was applied to determine statistically significant threshold values of MSol and MLogS_M. Results indicated that NMEs with MLogS_M > -3.05 or MSol > 0.30 mg/mL will have ≥85% probability of being highly soluble and new mol. entities with MLogS_M ≤ -3.05 or MSol ≤ 0.30 mg/mL will have ≥85% probability of being poorly soluble When comparing solubility classification using the threshold values of MLogS_M or MSol with BDDCS, we were able to correctly classify 85% of compounds We also evaluated solubility classification of an independent set of 108 orally administered drugs using MSol (0.3 mg/mL) and our method correctly classified 81% and 95% of compounds into high and low solubility classes, resp. The high/low solubility classification using MLogS_M or MSol is novel and independent of traditionally used dose number criteria.

International Journal of Pharmaceutics (Amsterdam, Netherlands) 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

Channabasavaraj, K. P. published the artcileDevelopment and validation of RP-HPLC method for estimation of varenicline tartrate in bulk drug and tablet dosage form, Computed Properties of 375815-87-5, the publication is International Journal of Pharmacy and Pharmaceutical Sciences (2011), 3(2), 59-61, database is CAplus.

A reverse phase high performance liquid chromatog. method was developed and validated for the estimation of varenicline tartrate in bulk and tablet using UV detector. Gradient chromatog. was performed on a C₁₈ column, with a mobile phase composed by methanol:potassium dihydrogen orthophosphate buffer pH 3 (50:50, volume/volume), at flow rate of 0.6 mL/min using UV detection at 237 nm. The retention time for Varenicline tartrate was found to be 2.966 min. Linearity of the method was found to be 10 to 50 μg/mL, with the regression coefficient of 0.9999. This method was validated according to ICH guidelines. The intra-day and inter day percentage relative standard deviation (RSD) was found 0.327 and 0.147 resp. The proposed method was successfully applied for the quant. determination of varenicline tartrate in tablet formulations.

International 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, Computed Properties of 375815-87-5.

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

Piyankarage, Sujeewa C. published the artcileAutomated Solid Phase Extraction and Polarity-Switching Tandem Mass Spectrometry Technique for High Throughput Analysis of Urine Biomarkers for 14 Tobacco-related Compounds, Recommanded Product: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, the publication is ACS Omega (2021), 6(46), 30901-30909, database is CAplus and MEDLINE.

Tobacco use is the leading preventable cause of premature disease and death in the United States. Approx., 34 million U.S. adults currently smoke cigarettes. We developed a method for automated sample preparation and liquid chromatog.-tandem mass spectrometry quantitation of 14 tobacco-related analytes: nicotine (NICF), cotinine (COTF), trans-3′-hydroxycotinine (HCTF), menthol glucuronide (MEG), anabasine (ANBF), anatabine (ANTF), isonicoteine (ISNT), myosmine (MYOS), beta-nicotyrine (BNTR), bupropion (BUPR), cytisine (CYTI), varenicline (VARE), arecaidine (ARD), and arecoline (ARL). The method includes automated solid-phase extraction using customized pos.-pressure functions. The preparation scheme has the capacity to process a batch of 96 samples within 4 h with greater than 88% recovery for all analytes. The 14 analytes, separated within 4.15 min using reversed-phase liquid chromatog., were determined using a triple-quadrupole mass spectrometer with atm.-pressure chem. ionization and multiple reaction monitoring in neg. and pos. ionization modes. Wide quantitation ranges, within 1.2-72,000 ng/mL, were established especially for COTF, HCTF, MEG, and NICF to quantify the broad range of biomarker concentrations found in the U.S. population. The method accuracy is above 90% while the overall imprecision is below 7%. Finally, we tested urine samples from 90 smokers and observed detection rates of over 98% for six analytes with urinary HCTF and MEG concentrations ranging from 200-14,100 and 60-57,100 ng/mL, resp. This high throughput anal. process can prepare and analyze a sample in 9 min and along with the 14-compound analyte panel can be useful for tobacco-exposure studies, in smoking-cessation programs, and for detecting changes in exposure related to tobacco products and their use.

ACS Omega 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

Dowling, Thomas C. published the artcileEvaluation of renal drug dosing: prescribing information and clinical pharmacist approaches, COA of Formula: C17H19N3O6, the publication is Pharmacotherapy (2010), 30(8), 776-786, database is CAplus and MEDLINE.

Study Objective: To characterize renal function parameters reported in United States Food and Drug Administration-approved prescribing information (package inserts), to compare dosage recommendations for patients with impaired renal function between prescribing information and tertiary drug dosing references, and to evaluate renal function quantification methods most commonly used by clin. pharmacists to develop dosage regimens. Design: Retrospective anal. and Web-based survey. Data Sources: Prescribing information for all new mol. entities (NMEs) approved from 1998-2007 in which dosing recommendations were proposed for patients with impaired renal function, drug monographs from four tertiary drug dosing references (Micromedex, Lexi-Comp, Epocrates Rx, and American Hospital Formulary Service [AHFS] Drug Information) for all identified NMEs, and a Web-based survey of 204 nephrol. and critical care pharmacy practitioners. Measurements and Main Results: A total of 44 NMEs included renal dosing recommendations in their prescribing information. For all 44 NMEs, prescribing information was reviewed to determine methods to quantify renal function, units of measure reported, and use of chronic kidney disease terminol. The most common index of renal function was creatinine clearance; the Cockcroft-Gault equation was specified in the prescribing information of 11 NMEs. Standardization for body weight was inconsistent, with prescribing information for four NMEs reporting renal function in ml/min/1.73 m². The prescribing information or tertiary sources did not mention use of estimated glomerular filtration rate (eGFR) or the Modification of Diet in Renal Disease Study (MDRD) equation. Epocrates Rx provided the most abbreviated renal dosing information, whereas AHFS Drug Information was the most comprehensive, and Lexi-Comp includes a renal function calculator. Nearly all (86%) clin. pharmacists indicated that automated eGFR is reported at their institutions, although they do not use these predictions for dosing in patients with impaired renal function, and their approaches to renal function estimation varied widely. Conclusion: Reporting of renal function methods and dosing recommendations for patients with impaired renal function requires standardization in order to ensure optimal dosing. Pharmacy clinicians do not substitute eGFR in place of creatinine clearance for renal dosing, which is consistent with current prescribing information. Studies are needed that will evaluate the validity of using eGFR to predict drug clearance and thereby generate dosage recommendations.

Pharmacotherapy 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

Kajiwara, Moto published the artcileRenal tubular secretion of varenicline by multidrug and toxin extrusion (MATE) transporters, Recommanded Product: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, the publication is Drug Metabolism and Pharmacokinetics (2012), 27(6), 563-569, database is CAplus and MEDLINE.

Multidrug and toxin extrusion (MATE) 1 and MATE2-K, H⁺/organic cation antiporters, are located at the brush-border membrane of renal proximal tubules. The present study aimed to clarify the role of MATE transporters in tubular secretion of varenicline. Varenicline at a dose of 5 mg/kg was administered to wild-type and Mate1-knockout mice via the jugular vein, and its uptake was measured by high-performance liquid chromatog. The renal secretory clearance of and systemic exposure to varenicline were significantly decreased (54.6%, p < 0.05) and increased (116%, p < 0.05) resp., by the genetic disruption of Mate1 in mice. Uptake of varenicline and [¹⁴C]tetraethylammonium (TEA) was examined in HEK293 cells transiently expressing the human (h) MATE1, hMATE2-K, mouse (m) MATE1, and hOCT2 basolateral organic cation transporter. [¹⁴C]TEA uptake in HEK293 cells expressing MATE transporters and hOCT2 was decreased in the presence of varenicline. The calculated IC₅₀ values for hMATE1, hMATE2-K, mMATE1, and hOCT2 were 62.2 ± 6.5, 122.3 ± 67.6, 255.0 ± 37.9, and 1,003.9 ± 135.8 (μM; mean ± S.E. for three sep. experiments), resp. Varenicline uptake was significantly increased in HEK293 cells expressing mMATE1, hMATE1, or hMATE2-K cDNA as well as hOCT2 compared to empty vector-transfected cells. In conclusion, renal MATE transporters were found to be responsible for renal tubular secretion of varenicline.

Drug Metabolism and Pharmacokinetics 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

Piestansky, Juraj published the artcileComparison of hydrodynamically closed two-dimensional capillary electrophoresis coupled with ultraviolet detection and hydrodynamically open capillary electrophoresis hyphenated with mass spectrometry in the bioanalysis of varenicline, Name: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, the publication is Journal of Separation Science (2017), 40(10), 2292-2303, database is CAplus and MEDLINE.

Two capillary electrophoresis methods for monitoring renally excreted varenicline, a highly effective drug prescribed for smoking cessation, in human urine were developed and compared. A method combining capillary electrophoresis with mass spectrometry was proposed for the fast anal. of varenicline (anal. time up to 7 min). Here, mass spectrometry was a prerequisite for achieving high sensitivity and selectivity of the anal. suitable for the quantification of a 15 ng/mL level of varenicline in un-pretreated urine matrixes. An alternative approach, two-dimensional (column-coupled) capillary electrophoresis with enhanced sample load capacity and UV detection, was proposed as a low-cost alternative to capillary electrophoresis with mass spectrometry. The isotachophoresis online sample treatment included simple elimination of the major matrix constituents and stacking of the sample in a large volume so that threefold lower quantitation limits could be easily achieved in comparison to the capillary electrophoresis with mass spectrometry. On the other hand, longer anal. time (ca. 4.5-fold) and more complex electrolyte system in the coupled zone electrophoresis step (including two additives enhancing separation selectivity, i.e. isopropanol and cyclodextrin) were prerequisites for the complete separation of varenicline from the sample matrix. Anyway, both the developed methods were validated according to the Food and Drug Administration guidelines showing favorable performance parameters, suitable for their routine biomedical use.

Journal of Separation Science 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, Name: 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

Cao, Qi published the artcileMechanism research on CSE restraining macrophages into foam cells by calcium sensing receptor, Quality Control of 226878-01-9, the publication is Xiandai Yufang Yixue (2015), 42(19), 3555-3559, 3596, database is CAplus.

Objective To confirm calcium sensing receptor (CaR) can increase the expression of CSE and the secretion of H₂S, thereby inhibiting the transformation of macrophages into foam cells. Methods Sensitive sulfur electrodes method was used to detect the change of the H₂S content in macrophages. The relative content of pos. cells was tested by oil red O staining and the HPLC method was sued to do the determination of intracellular cholesterol content. ELISA assay detected the secretion situation of cytokine IL-10, MIF, and TNF-α. The expression of CaR, CSE, CD36 and ACAT-1 in each group cells were detected by Western blot. Results Compared with the blank control group, the relative contents of H₂S in the GdCl₃ group and the NaHS group significantly increased, while the NPS2390 group, the relative content of H₂S significantly decreased. The number of pos. cells in the GdCl₃ group and the NaHS group obviously decreased, while the number in NPS2390 group adversely increased. The levels of TNF-α and MIF in cell supernatant significantly ascended, and the IL-10 level fell in the GdCl₃ and NaHS groups. However, there was a rising trend on the levels of TNF-α and MIF in cell supernatant, and the IL-10 level dropped significantly in the NPS2390 group. The expression of CaR and CSE significantly enhanced in GdCl₃ group, while the expression of CD36 and ACAT-1 were significantly inhibited in GdCl₃ group. Meanwhile, the expressions of CaR and CSE were significantly inhibited in NPS2390 group, while the expression of CD36 and ACAT-1 were significantly enhanced in NPS2390 group. GdCl₃ group significantly increased the expression of CSE, while GdCl₃ + CSE siRNA group and CSE siRNA group significantly reduced the expression of CSE. GdCl₃ group significantly increased the relative content of H₂S, while GdCl₃ + CSE siRNA group and CSE siRNA group significantly reduced the relative content of H₂S. Conclusion CaR could enhance the expression of CSE in macrophages to increase the secretion of H₂S, thereby inhibiting the transformation of macrophages into foam cells.

Xiandai Yufang Yixue 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, Quality Control of 226878-01-9.

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

Liu, Cong published the artcileThe extracellular calcium-sensing receptor promotes porcine egg activation via calcium/calmodulin-dependent protein kinase II, Recommanded Product: N-(Adamantan-1-yl)quinoxaline-2-carboxamide, the publication is Molecular Reproduction & Development (2020), 87(5), 598-606, database is CAplus and MEDLINE.

Extracellular calcium is required for intracellular Ca²⁺ oscillations needed for egg activation, but the regulatory mechanism is still poorly understood. The present study was designed to demonstrate the function of calcium-sensing receptor (CASR), which could recognize extracellular calcium as first messenger, during porcine egg activation. CASR expression was markedly upregulated following egg activation. Functionally, the addition of CASR agonist NPS R-568 significantly enhanced pronuclear formation rate, while supplementation of CASR antagonist NPS2390 compromised egg activation. There was no change in NPS R-568 group compared with control group when the egg activation was performed without extracellular calcium addition The addition of NPS2390 precluded the activation-dependent [Ca²⁺]_i rise. When egg activation was conducted in intracellular Ca²⁺ chelator BAPTA-AM and NPS R-568 containing medium, CASR function was abolished. Meanwhile, CASR activation increased the level of the [Ca²⁺]_i effector p-CAMKII, and the presence of KN-93, an inhibitor of CAMKII, significantly reduced the CASR-mediated increasement of pronuclear formation rate. Furthermore, the increase of CASR expression following activation was reversed by inhibiting CAMKII activity, supporting a pos. feedback loop between CAMKII and CASR. Altogether, these findings provide a new pathway of egg activation about CASR, as the extracellular Ca²⁺ effector, promotes egg activation via its downstream effector and upstream regulator CAMKII.

Molecular Reproduction & Development 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, Recommanded Product: N-(Adamantan-1-yl)quinoxaline-2-carboxamide.

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