Category: quinoxaline

Zhang, Wei-hua published the artcileCalcium sensing receptor is involved in neonate rat cardiomyocyte apoptosis induced by hypoxia/reoxygenation via regulating calcium concentration in mitochondria, Formula: C19H21N3O, the publication is Harbin Yike Daxue Xuebao (2012), 46(6), 534-538, database is CAplus.

Calcium sensing receptor (CaR) activation plays a role in the regulation of SR-mitochondrial inter-organelle Ca²⁺ signaling, causing apoptosis during ischemia/reperfusion (I/R). Neonatal rat cardiomyocytes were subjected to 3 h of hypoxia, followed by 6 h of reoxygenation. Ca²⁺ m were determined using x-rhod-1 and the mitochondrial membrane potential was detected with JC-1 during reoxygenation. The apoptotic rates detected by Hoechst33342 were lower in NPS-2390 + Ca + Ni + Cd + H-Re (±4)%, 2-APB + Ca + Ni + Cd + H-Re (18±4)% and Ru + Ca + Ni + Cd + H-Re (23±5)% groups than H-Re (33±6)%, Ca+Ni+Cd+H-Re (31±5)% and Gd+Ni+Cd+HRe (34±3)% groups. [Ca ²⁺] m was increased in the Ca + Ni + Cd + H-Re group. The mitochondria transmembrane potential was lower in Ca + Ni + Cd + H-Re group than that in 2-APB + Ca + Ni + Cd + H-Re and Ru + Ca + Ni + Cd + H-Re groups. CaR activation causes Ca²⁺ release from the SR into the mitochondria through IP3 Rs and induces cardiomyocyte apoptosis during hypoxia/reoxygenation.

Harbin Yike Daxue Xuebao 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 C25H23NO4, Formula: C19H21N3O.

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

Colgan, Stephen T. published the artcileUse of Activated Carbon in Packaging to Attenuate Formaldehyde-Induced and Formic Acid-Induced Degradation and Reduce Gelatin Cross-Linking in Solid Dosage Forms, Category: quinoxaline, the publication is Journal of Pharmaceutical Sciences (2016), 105(7), 2027-2031, database is CAplus and MEDLINE.

Formaldehyde and formic acid are reactive impurities found in commonly used excipients and can be responsible for limiting drug product shelf-life. Described here is the use of activated carbon in drug product packaging to attenuate formaldehyde-induced and formic acid-induced drug degradation in tablets and crosslinking in hard gelatin capsules. Several pharmaceutical products with known or potential vulnerabilities to formaldehyde-induced or formic acid-induced degradation or gelatin crosslinking were subjected to accelerated stability challenges in the presence and absence of activated carbon. The effects of time and storage conditions were determined For all of the products studied, activated carbon attenuated drug degradation or gelatin crosslinking. This novel use of activated carbon in pharmaceutical packaging may be useful for enhancing the chem. stability of drug products or the dissolution stability of gelatin-containing dosage forms and may allow for the (1) extension of a drug product’s shelf-life when the limiting attribute is a degradation product induced by a reactive impurity, (2) marketing of a drug product in hotter and more humid climatic zones than currently supported without the use of activated carbon, and (3) enhanced dissolution stability of products that are vulnerable to gelatin crosslinking.

Journal of 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, Category: quinoxaline.

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

Zhang, Tao published the artcileAssessing Food Effects on Oral Drug Absorption Based on the Degree of Renal Excretion, Recommanded Product: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, the publication is AAPS Journal (2021), 23(3), 47, database is CAplus and MEDLINE.

Food intake influences the pharmacokinetics of orally administered drugs by altering drug absorption, metabolism, and excretion. A drug which is mainly excreted into urine as parent drug is usually highly water-soluble and metabolically stable. Food intake is not expected to significantly affect its extent of oral absorption, metabolism, and excretion. Therefore, we hypothesize that an orally administered drug with significant renal excretion should not have a dramatic food effect (FE). To test our hypothesis, we summarized the FE for orally administered immediate-release (IR) and modified-release (MR) formulations approved by the US FDA from 1998 to 2019, focusing on drugs undergoing significant renal excretion. Totally, 98 active pharmaceutical ingredients (APIs) in IR formulations and 34 APIs in MR formulations were selected. The results demonstrate that the area-under-the-curve (AUC) for IR drug products with f_{ur_cunchanged_cpo} > 10% is unlikely to be affected by food, although the peak plasma concentration (C_max) may increase or decrease by up to 50%. Compared with IR drug products with f_{ur_cunchanged_cpo} > 10%, MR drug products with f_{ur_cunchanged_cpo} > 10% tend to have more significant FE. Although our proposed approach cannot substitute a clin. FE study, it could be a useful addition to early drug development to get an initial sense of the potential for FE for a drug candidate.

AAPS Journal 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 C9H17NO, 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

Anonymous published the artcileA condensation product between 5,8,14-triazatetracyclo[10.3.1.02,11.04,9]hexadeca-2(11),3,5,7,9-pentaene and lactose, Computed Properties of 375815-87-5, the publication is IP.com Journal (2009), 9(3B2), 2, database is CAplus.

A reaction of L-tartaric acid with 7,8,9,10-tetrahydro-6,10-methano-6H-pyrazino[2,3-h][3]benzazepine (Chantix, varenicline) provided Chantix L-tartrate. A reaction of that compound with lactose [i.e., 4-O-β-D-galactopyranosyl-D-glucose] gave a mixture of 4-O-[6-(7,8,9,10-tetrahydro-6,10-methano-6H-pyrazino[2,3-h][3]benzazepin-8-yl)-β-D-galactopyranosyl]-β-D-glucopyranose and 4-O-(β-D-galactopyranosyl)-6-deoxy-6-(7,8,9,10-tetrahydro-6,10-methano-6H-pyrazino[2,3-h][3]benzazepin-8-yl)-β-D-glucopyranose.

IP.com Journal 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

Ericson, Jon F. published the artcileEvaluation of the OECD 314B Activated Sludge Die-Away Test for Assessing the Biodegradation of Pharmaceuticals, Name: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, the publication is Environmental Science & Technology (2010), 44(1), 375-381, database is CAplus and MEDLINE.

The European Medicines Agency guideline for the environmental risk assessment of medicinal products provides a step-by-step phased approach to evaluate the potential risks of new medicines to the environment. Phase I (prescreen) estimates the initial exposure of the new medicine in the environment. Phase II A (screen) estimates the fate and effects in the environment. The fate screen determines the inherent properties of the new medicinal active ingredient to sorb to sludge, soil, and sediment matrixes and its potential to degrade in a sewage treatment plant and in the subsequent water-sediment compartment. Current ERA Guidance (2006) recommends the OECD 301B Ready Biodegradation Test for Phase II Tier A testing without a clear recommendation for Phase II Tier B testing when further refinement may be needed. With the recent approval of the OECD 314B method for activated sludge, there is now an alternative test method that may be better suited for Phase II Tier A testing and to the data needs of the ERA. As a batch test, it fits the needs of a Tier A screen. It is not designed to simulate the operational steps of a sewage treatment plant, such as the OECD 303 tests, and yet provides the following without considerable costs or resources of OECD 303: (1) useful kinetic information in a test that reflects the conditions of the sewage-treatment environment, i.e., realistic biomass solids concentrations and low level test material concentrations to simulate 1st-order (nongrowth) kinetics, (2) mass balance anal. for CO₂ evolution and for residues found in mixed liquor, (3) use of an abiotic control to assess losses other than those attributed to biotic biodegradation, and (4) biotransformation profile of degradants. This paper presents the results of OECD 301B with that of OECD 314B for activated sludge biodegradation for 5 Pfizer drug substances. The use of this new method as an alternative to OECD 301B would strengthen the fate testing screen in Phase II Tier A of the EMEA ERA. It would provide a characterization of a substance’s potential for biotransformation and mineralization during sewage treatment and provide a means for revising predicted environmental concentration of surface water for amount removed during sewage treatment.

Environmental Science & Technology 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

Maklad, Noha published the artcilePositive and negative modulation of group 1 metabotropic glutamate receptors, Name: N-(Adamantan-1-yl)quinoxaline-2-carboxamide, the publication is Chemtracts (2008), 21(5), 165-171, database is CAplus.

A review. Vanejevs et al. developed a pharmacophore hypothesis using potent and com. available metabotropic glutamate receptor 1 (mGluR1) analogs. This was done by aligning the potent and com. available mGluR1 antagonists using the flexible alignment tool included in the Mol. Operating Environment software. The developed pharmacophore model offers a new and different methodol. to discover such analogs.

Chemtracts 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, Name: N-(Adamantan-1-yl)quinoxaline-2-carboxamide.

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

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

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

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