Heterocyclic Building Blocks-quinoxaline

Kim, Eunwoo published the artcilePharmacokinetic comparison between tablet of varenicline tartrate and orally disintegrating film of varenicline salicylate in healthy subjects, Related Products of quinoxaline, the publication is International Journal of Clinical Pharmacology and Therapeutics (2021), 59(6), 478-484, database is CAplus and MEDLINE.

Varenicline is an efficacious aid for smoking cessation. In this study, the pharmacokinetics and safety were compared between film-coated tablets of varenicline tartrate (reference drug) and the newly developed orally disintegrating films of varenicline salicylate (test drug), both of them contained 1 mg of varenicline. A randomized, open-label, single-dose, two-sequence, two-period crossover study was conducted in healthy male subjects. Serial blood samples were obtained for up to 72 h in each period, with a washout period of 7 days or more. The pharmacokinetic parameters were calculated using the noncompartmental method. Safety profiles were assessed throughout the study. A total of 28 subjects completed the study. The plasma varenicline concentration-time profiles were similar for the two study drugs. The maximum plasma varenicline concentration (Cmax) was 5,768.95 ng/L (mean) and 5,780.55 ng/L for the test drug and reference drug, resp. The areas under the concentration-time curve from time 0 to the last measurable time point (AUC0 – t) were 94,086.30 h x ng/L and 89,958.55 h x ng/L for the test drug and reference drug, resp. The geometric mean ratios (90% confidence intervals) of the test drug to the reference drug for Cmax and AUC0 – t were 0.9955 (0.9488 – 1.0444) and 1.0449 (0.9848 – 1.1088), resp., which fell within the bioequivalence range of 0.8 – 1.25. There was no difference in safety between the study drugs. The pharmacokinetics and safety profiles were similar between the two study drugs. The orally disintegrating film of varenicline salicylate can be an alternative to varenicline tartrate tablets.

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, Related Products of quinoxaline.

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

Murphy, Brendan J. published the artcileVarenicline L-tartrate crystal forms: Characterization through crystallography, spectroscopy, and thermodynamics, SDS of cas: 375815-87-5, the publication is Journal of Pharmaceutical Sciences (2010), 99(6), 2766-2776, database is CAplus and MEDLINE.

This research utilized crystallog., spectroscopic, and thermal anal. data to assess the thermodn. stability relationship between the three known crystal forms of Varenicline L-tartrate. Of the two anhydrous forms (Forms A and B), Form B was determined to be the stable form at 0 K based on its calculated true d., hydrogen bonding in the crystal lattice, and application of the IR rule. Form A has a higher m.p. and higher solubility at room temperature as compared to Form B, indicating that these forms are enantiotropically related. Application of the eutectic-melting method enabled accurate determination of the transition temperature (63°), with Form B as the stable anhydrous form at room temperature The stability relationships between the anhydrous polymorphs and the monohydrate (Form C) were assessed through exposure of the anhydrous forms to a range of water vapor pressures at room temperature A phase boundary was identified, with the monohydrate being the thermodynamically stable form above critical water activity values of 0.85 and 0.94 for Forms A and B, resp. These results provide a better understanding of the form stability as it relates to normal manufacturing and storage conditions for the active pharmaceutical ingredient and drug product. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 2766-2776, 2010.

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, SDS of cas: 375815-87-5.

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

Kurosawa, Toshiki published the artcileInvolvement of Proton-Coupled Organic Cation Antiporter in Varenicline Transport at Blood-Brain Barrier of Rats and in Human Brain Capillary Endothelial Cells, Application of 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, the publication is Journal of Pharmaceutical Sciences (2017), 106(9), 2576-2582, database is CAplus and MEDLINE.

Varenicline is a selective partial α₄β₂ nicotinic acetylcholine receptor agonist, which is used to help achieve smoking cessation. Here, we investigated varenicline transport at the blood-brain barrier by means of in vivo microdialysis, in situ brain perfusion, and brain efflux index measurements in rats, and in vitro uptake studies in human brain capillary endothelial cells. Microdialysis demonstrated that varenicline is actively transported from blood to brain in rats. Blood-to-brain uptake transport of varenicline, as measured by the in situ brain perfusion technique, was strongly inhibited by diphenhydramine, a potent inhibitor of proton-coupled organic cation (H⁺/OC) antiporter. However, brain efflux index study showed that brain-to-blood efflux transport of varenicline was not inhibited by diphenhydramine. In human brain capillary endothelial cells, varenicline was taken up time- and concentration-dependently. The uptake was dependent on an oppositely directed proton gradient, but was independent of extracellular sodium and membrane potential. The uptake was inhibited by a metabolic inhibitor, and by substrates of H⁺/OC antiporter, but not by substrates or inhibitors of OCTs, OCTNs, PMAT, and MATE1, which are known organic cation transporters. The present results suggest that the H⁺/OC antiporter contributes predominantly to varenicline uptake at the blood-brain barrier.

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, 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

Rollema, Hans published the artcilePreclinical pharmacology of the α4β2 nAChR partial agonist varenicline related to effects on reward, mood and cognition, Related Products of quinoxaline, the publication is Biochemical Pharmacology (2009), 78(7), 813-824, database is CAplus and MEDLINE.

The pharmacol. properties and pharmacokinetic profile of the α4β2 nicotinic acetylcholine receptor (nAChR) partial agonist varenicline provide an advantageous combination of free brain levels and functional potencies at the target receptor that for a large part explain its efficacy as a smoking cessation aid. Since α4β2 and other nAChR subtypes play important roles in mediating central processes that control reward, mood, cognition and attention, there is interest in examining the effects of selective nAChR ligands such as varenicline in preclin. animal models that assess these behaviors. Here we describe results from studies on varenicline’s effects in animal models of addiction, depression, cognition and attention and discuss these in the context of recently published preclin. and preliminary clin. studies that collected data on varenicline’s effects on mood, cognition and alc. abuse disorder. Taken together, the preclin. and the limited clin. data show beneficial effects of varenicline, but further clin. studies are needed to evaluate whether the preclin. effects observed in animal models are translatable to the clinic.

Biochemical Pharmacology 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.

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

Rollema, Hans published the artcileVarenicline has antidepressant-like activity in the forced swim test and augments sertraline’s effect, SDS of cas: 375815-87-5, the publication is European Journal of Pharmacology (2009), 605(1-3), 114-116, database is CAplus and MEDLINE.

Varenicline, an α4β2 nicotinic acetylcholine receptor partial agonist developed as a smoking cessation aid, showed antidepressant-like activity in the forced swim test in two mouse strains. In addition, a low varenicline dose significantly enhanced the effects of moderately active doses of the selective serotonin reuptake inhibitor sertraline. These findings are consistent with the notion that reducing α4β2 nicotinic acetylcholine receptor activity either by antagonists or by partial agonists that can partially activate or desensitize acetylcholine receptors is associated with antidepressant-like properties. These data suggest that varenicline may have antidepressant potential and can, when combined, augment antidepressant responses of selective serotonin reuptake inhibitors.

European Journal of Pharmacology 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

Brunner, Joseph I. published the artcilePharmacological Validation of Candidate Causal Sleep Genes Identified in an N2 Cross, COA of Formula: C17H19N3O6, the publication is Journal of Neurogenetics (2011), 25(4), 167-181, database is CAplus and MEDLINE.

Despite the substantial impact of sleep disturbances on human health and the many years of study dedicated to understanding sleep pathologies, the underlying genetic mechanisms that govern sleep and wake largely remain unknown. Recently, the authors completed large-scale genetic and gene expression analyses in a segregating inbred mouse cross and identified candidate causal genes that regulate the mammalian sleep-wake cycle, across multiple traits including total sleep time, amounts of rapid eye movement (REM), non-REM, sleep bout duration, and sleep fragmentation. Here the authors describe a novel approach toward validating candidate causal genes, while also identifying potential targets for sleep-related indications. Select small-mol. antagonists and agonists were used to interrogate candidate causal gene function in rodent sleep polysomnog. assays to determine impact on overall sleep architecture and to evaluate alignment with associated sleep-wake traits. Significant effects on sleep architecture were observed in validation studies using compounds targeting the muscarinic acetylcholine receptor M3 subunit (Chrm3) (wake promotion), nicotinic acetylcholine receptor alpha4 subunit (Chrna4) (wake promotion), dopamine receptor D5 subunit (Drd5) (sleep induction), serotonin 1D receptor (Htr1d) (altered REM fragmentation), glucagon-like peptide-1 receptor (Glp1r) (light sleep promotion and reduction of deep sleep), and calcium channel, voltage-dependent, T type, alpha 1I subunit (Cacna1i) (increased bout duration of slow wave sleep). Taken together, these results show the complexity of genetic components that regulate sleep-wake traits and highlight the importance of evaluating this complex behavior at a systems level. Pharmacol. validation of genetically identified putative targets provides a rapid alternative to generating knock out or transgenic animal models, and may ultimately lead towards new therapeutic opportunities.

Journal of Neurogenetics 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

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

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

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