M.W=350-400| Heterocyclic Building Blocks-quinoxaline

Przybylak, Katarzyna R.’s team published research in Journal of Chemical Information and Modeling in 54 | CAS: 375815-87-5

Journal of Chemical Information and Modeling 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, Formula: C17H19N3O6.

Przybylak, Katarzyna R. published the artcileHow Does the Quality of Phospholipidosis Data Influence the Predictivity of Structural Alerts?, Formula: C17H19N3O6, the publication is Journal of Chemical Information and Modeling (2014), 54(8), 2224-2232, database is CAplus and MEDLINE.

The ability of drugs to induce phospholipidosis (PLD) is linked directly to their mol. substructures: hydrophobic, cyclic moieties with hydrophilic, peripheral amine groups. These structural properties can be captured and coded into SMILES arbitrary target specification (SMARTS) patterns. Such structural alerts, which are capable of identifying potential PLD inducers, should ideally be developed on a relatively large but reliable data set. We had previously developed a model based on SMARTS patterns consisting of 32 structural fragments using information from 450 chems. In the present study, addnl. PLD structural alerts have been developed based on a newer and larger data set combining two data sets published recently by the United States Food and Drug Administration (US FDA). To assess the predictive performance of the updated SMARTS model, two publicly available data sets were considered. These data sets were constructed using different criteria and hence represent different standards for overall quality. In the first data set high quality was assured as all neg. chems. were confirmed by the gold standard method for the detection of PLD-transmission electron microscopy (EM). The second data set was constructed from seven previously published data sets and then curated by removing compounds where conflicting results were found for PLD activity. Evaluation of the updated SMARTS model showed a strong, pos. correlation between predictive performance of the alerts and the quality of the data set used for the assessment. The results of this study confirm the importance of using high quality data for modeling and evaluation, especially in the case of PLD, where species, tissue, and dose dependence of results are addnl. confounding factors.

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

Levy, Jeffrey N.’s team published research in Journal of the American Chemical Society in 142 | CAS: 375815-87-5

Journal of the American Chemical Society 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.

Levy, Jeffrey N. published the artcileSelective Halogenation of Pyridines Using Designed Phosphine Reagents, COA of Formula: C17H19N3O6, the publication is Journal of the American Chemical Society (2020), 142(25), 11295-11305, database is CAplus and MEDLINE.

Halopyridines are key building blocks for synthesizing pharmaceuticals, agrochems., and ligands for metal complexes, but strategies to selectively halogenate pyridine C-H precursors are lacking. We designed a set of heterocyclic phosphines that are installed at the 4-position of pyridines as phosphonium salts and then displaced with halide nucleophiles. A broad range of unactivated pyridines can be halogenated, and the method is viable for late-stage halogenation of complex pharmaceuticals. Computational studies indicate that C-halogen bond formation occurs via an S_NAr pathway, and phosphine elimination is the rate-determining step. Steric interactions during C-P bond cleavage account for differences in reactivity between 2- and 3-substituted pyridines.

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

El-Bagary, Ramzia I.’s team published research in Talanta in 146 | CAS: 375815-87-5

Talanta 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.

El-Bagary, Ramzia I. published the artcileNovel liquid chromatographic methods for the determination of varenicline tartrate, Product Details of C17H19N3O6, the publication is Talanta (2016), 83-92, database is CAplus and MEDLINE.

Two simple, sensitive, rapid, and stability-indicating liquid chromatog. (LC) methods have been developed for the determination of varenicline tartrate. They comprised the determination of varenicline (VRC) in the presence of its oxidative degradates and related impurity (N-formyl varenicline) (NFV). The first method was a LC with diode array detection (DAD) at 235 nm using Ristek-Ultra C₁₈ column (100 mm×2.1 mm, 5 μm). Isocratic elution of VRC was employed using a mobile phase consisting of buffer mixture (1.2% potassium dihydrogen phosphate and 0.08% octane sulfonic acid): acetonitrile (86:14, volume/volume), pH (5.0). In the second method; a fluorimetric detection technique was developed, based on precolumn derivatization of VRC using 7-chloro-4-nitrobenzo-2-oxa-1, 3-diazole (NBD-Cl). The fluorescence detector (FLD) was operated at 474 nm for excitation and 539 nm for emission. Isocratic elution was applied with a mobile phase consisting of methanol-distilled water (70:30, volume/volume). Separation was achieved using Symmetry Waters C₁₈ column (150 mm×4.6 mm, 5 μm). Linearity, accuracy and precision were found to be acceptable over the concentration ranges of 0.5-20.0 μg mL^-1 and 0.2-20.0 μg mL^-1 with the first and the second method, resp. The optimized methods were validated and proved to be specific, simple, and accurate for the quality control of the drug in its pharmaceutical preparation

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

Rollema, Hans’s team published research in Neurochemistry International in 58 | CAS: 375815-87-5

Neurochemistry International 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.

Rollema, Hans published the artcileEffect of co-administration of varenicline and antidepressants on extracellular monoamine concentrations in rat prefrontal cortex, HPLC of Formula: 375815-87-5, the publication is Neurochemistry International (2011), 58(1), 78-84, database is CAplus and MEDLINE.

Since a substantial proportion of smokers have comorbid mood disorders, the smoking cessation aid varenicline might occasionally be prescribed to patients who are simultaneously treated with antidepressants. Given that varenicline is a selective nicotinic acetylcholine receptor partial agonist and not a substrate or inhibitor of drug metabolizing enzymes, pharmacokinetic interactions with various classes of antidepressants are highly unlikely. It is, however, conceivable that varenicline may have a pharmacodynamic effect on antidepressant-evoked increases in central monoamine release. Interactions resulting in excessive transmitter release could cause adverse events such as serotonin syndrome, while attenuation of monoamine release could impact the clin. efficacy of antidepressants. To investigate this we examined whether varenicline administration modulates the effects of the selective serotonin reuptake inhibitor sertraline and the monoamine oxidase inhibitor clorgyline, given alone and combined, on extracellular concentrations of the monoamines serotonin, dopamine, and norepinephrine in rat brain by microdialysis. Given the important role attributed to cortical monoamine release in serotonin syndrome as well as antidepressant activity, the effects on extracellular monoamine concentrations were measured in the medial prefrontal cortex. Responses to maximally EDs of sertraline or clorgyline and of sertraline plus clorgyline were the same in the absence as in the presence of a relatively high dose of varenicline, which by itself had no significant effect on cortical monoamine release. This is consistent with the binding profile of varenicline that has insufficient affinity for receptors, enzymes, or transporters to inhibit or potentiate the pharmacol. effects of antidepressants. Since varenicline neither diminished nor potentiated sertraline- or clorgyline-induced increases in neurotransmitter levels, combining varenicline with serotonergic antidepressants is unlikely to cause excessive serotonin release or to attenuate antidepressant efficacy via effects on cortical serotonin, dopamine or norepinephrine release.

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

Carson, Kristin V.’s team published research in Lung Cancer Management in 2 | CAS: 375815-87-5

Lung Cancer Management 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.

Carson, Kristin V. published the artcileSmoking cessation interventions for lung cancer patients, Computed Properties of 375815-87-5, the publication is Lung Cancer Management (2013), 2(1), 61-74, database is CAplus.

A review. SUMMARY Worldwide, lung cancer contributes to over 1.4 million deaths per yr. Smoking cessation is strongly recommended in clin. practice guidelines for lung cancer management, yet evidence suggests a translational gap between evidence and practice. There are significant health benefits following smoking cessation even after a short period of time. Long-term implications for lung cancer patients include improvements in quality of life, reductions in postoperative complications and reductions in 12-mo mortality. Evidence suggests that combining pharmacotherapy, in particular varenicline tartrate (varenicline), with cognitive and behavioral interventions offers the best opportunity for successful long-term abstinence. This review summarizes the latest evidence for smoking cessation interventions in lung cancer patients, identifies gaps in current clin. practice and highlights priority areas for future research.

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

Mocking, Roel J. T.’s team published research in Psychopharmacology (Heidelberg, Germany) in 231 | CAS: 375815-87-5

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 C17H19N3O6, Related Products of quinoxaline.

Mocking, Roel J. T. published the artcileEffects of short-term varenicline administration on cortisol in healthy, non-smoking adults: a randomized, double-blind, study, Related Products of quinoxaline, the publication is Psychopharmacology (Heidelberg, Germany) (2014), 231(1), 143-148, database is CAplus and MEDLINE.

Rationale: Varenicline is the most effective drug for smoking cessation, but its use decreased because of reports of depressogenic side effects. However, because smoking and smoking cessation on their own are associated with depression, it remains unclear whether reported depressogenic effects are attributable to varenicline, or to smoking, and/or smoking cessation themselves. Objectives: Previously, we observed no depressogenic effects of varenicline on a psychol. level. In the present study, we aimed at investigating potential depressogenic effects of the partial nicotinergic acetylcholine receptor agonist varenicline on a biol. level. A possible pathway would be an effect of varenicline on the hypothalamic-pituitary-adrenal (HPA) axis, considering the relation between the HPA axis and (1) the cholinergic system and (2) depression. Methods: In a randomized, double-blind design, we administered varenicline or placebo for 7 days (0.5 mg/day first 3 days, then 1 mg/day) to healthy never-smoking subjects, thereby eliminating bias by (previous) smoking status. We used repeated measures (before and after treatment) of the salivary free cortisol awakening response to measure HPA axis activity and flexibility. Results: Salivary cortisol data of 34 subjects were included in the anal. Results showed no effect of varenicline on height (F_1,32 = 0.405; P = 0.529) or shape (F_2,31 = 0.110; P = 0.164) of the cortisol awakening response. Conclusions: Results do not suggest depressogenic effects of varenicline on the HPA axis. Although this does not preclude other biol. depressogenic effects of varenicline, it seems that concerns about effects of varenicline on the HPA axis should not limit its potential to treat nicotine and related addictions.

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

Slavov, Svetoslav H.’s team published research in Bioorganic & Medicinal Chemistry in 22 | CAS: 375815-87-5

Bioorganic & Medicinal Chemistry 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 C9H10N2O, Recommanded Product: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate.

Slavov, Svetoslav H. published the artcileComputational identification of a phospholipidosis toxicophore using ¹³C and ¹⁵N NMR-distance based fingerprints, Recommanded Product: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, the publication is Bioorganic & Medicinal Chemistry (2014), 22(23), 6706-6714, database is CAplus and MEDLINE.

Modified 3D-SDAR fingerprints combining ¹³C and ¹⁵N NMR chem. shifts augmented with inter-at. distances were used to model the potential of chems. to induce phospholipidosis (PLD). A curated dataset of 328 compounds (some of which were cationic amphiphilic drugs) was used to generate 3D-QSDAR models based on tessellations of the 3D-SDAR space with grids of different d. Composite PLS models averaging the aggregated predictions from 100 fully randomized individual models were generated. On each of the 100 runs, the activities of an external blind test set comprised of 294 proprietary chems. were predicted and averaged to provide composite estimates of their PLD-inducing potentials (PLD+ if PLD is observed, otherwise PLD-). The best performing 3D-QSDAR model utilized a grid with a d. of 8 ppm × 8 ppm in the C-C region, 8 ppm × 20 ppm in the C-N region and 20 ppm × 20 ppm in the N-N region. The classification predictive performance parameters of this model evaluated on the basis of the external test set were as follows: accuracy = 0.70, sensitivity = 0.73 and specificity = 0.66. A projection of the most frequently occurring bins on the standard coordinate space suggested a toxicophore composed of an aromatic ring with a centroid 3.5-7.5 Å distant from an amino-group. The presence of a second aromatic ring separated by a 4-5 Å spacer from the first ring and at a distance of between 5.5 Å and 7 Å from the amino-group was also associated with a PLD+ effect. These models provide comparable predictive performance to previously reported models for PLD with the added benefit of being based entirely on non-confidential, publicly available training data and with good predictive performance when tested in a rigorous, external validation exercise.

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

Pei, Gaofeng’s team published research in Fundamental Research in 2 | CAS: 375815-87-5

Fundamental Research 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.

Pei, Gaofeng published the artcileCEBIT screening for inhibitors of the interaction between SARS-CoV-2 spike and ACE2, Category: quinoxaline, the publication is Fundamental Research (2022), 2(4), 562-569, database is CAplus.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, causing COVID-19, is the most challenging pandemic of the modern era. It has resulted in over 5 million deaths worldwide. To quickly explore therapeutics for COVID-19, we utilized a previously-established system, namely CEBIT. We performed a high-throughput screening of FDA-approved drugs to inhibit the interaction between the receptor-binding domain (RBD) of SARS-CoV-2 spike protein and its obligate receptor ACE2. This interaction is essential for viral entry and therefore represents a promising therapeutic target. Based on the recruitment of interacting mols. into phase-separated condensates as a readout, we identified six pos. candidates from a library of 2572 compounds, most of which have been reported to inhibit the entry of SARS-CoV-2 into host cells. Our surface plasmon resonance (SPR) and mol. docking analyses revealed the possible mechanisms via which these compounds interfere with the interaction between RBD and ACE2. Hence, our results indicate that CEBIT is highly versatile for identifying drugs against SARS-CoV-2 entry, and targeting CoV-2 entry by small mol. drugs is a viable therapeutic option to treat COVID-19 in addition to commonly used monoclonal antibodies.

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

Xun, Caifang’s team published research in Spectroscopy Letters in 49 | CAS: 375815-87-5

Spectroscopy Letters 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 C11H12O4, Related Products of quinoxaline.

Xun, Caifang published the artcileInteraction between varenicline tartrate and bovine serum albumin, Related Products of quinoxaline, the publication is Spectroscopy Letters (2016), 49(4), 304-310, database is CAplus.

This paper mainly investigated the interaction between varenicline tartrate and bovine serum albumin. The Stern-Volmer quenching constant and bimol. quenching rate constant were determined; furthermore, the fluorescence quenching mechanism between varenicline tartrate and bovine serum albumin was clarified. The binding constants and the number of binding sites were deduced from the double logarithm regression curve. Thermodn. parameters were calculated, which indicated that the binding process was spontaneous and the acting force were mainly hydrophobic forces. The binding distance was calculated to be 4.80 nm, which means that there was nonradiative energy transfer from varenicline tartrate to bovine serum albumin during the process. And the bovine serum albumin conformation affected by varenicline tartrate was analyzed through UV-visible and synchronous fluorescence spectroscopy.

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

Colgan, Stephen T.’s team published research in Journal of Pharmaceutical Sciences in 105 | CAS: 375815-87-5

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.

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.

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