Tag: M.W=350-400

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

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

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

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

Sarioglu, Nurhan published the artcileThe effects of bronchodilator drugs and antibiotics used for respiratory infection on human erythrocyte carbonic anhydrase I and II isozymes, Safety of 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, the publication is Archives of Physiology and Biochemistry (2015), 121(2), 56-61, database is CAplus and MEDLINE.

Carbonic anhydrase (CA) is an enzyme which plays role/roles in various homeostatic mechanisms, such as the acid-base balance and electrolyte secretion in various tissues. This study aimed to determine and to compare possible alterations in activity of this enzyme caused by use of bronchodilator drugs and respiratory infection antibiotics. CA I and II were purified from human erythrocytes by a simple one step procedure using Sepharose 4B-L-tyrosine-sulfonamide affinity column. The iso-enzymes were purified 259.16-fold with a yield of 31.74%. CAI and II isoenzymes were treated with several drugs, then the inhibition or activation of the enzymes were determined The results of this study show that itrapropium bromide is the most effective inhibitor for human erythrocytes carbonic anhydrase compared with the other bronchodilator drugs.

Archives of Physiology and Biochemistry 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, Safety 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

Raleigh, Michael D. published the artcileAttenuating nicotine’s effects with high affinity human anti-nicotine monoclonal antibodies, Synthetic Route of 375815-87-5, the publication is PLoS One (2021), 16(7), e0254247, database is CAplus and MEDLINE.

Use of nicotine-specific monoclonal antibodies (mAbs) to sequester and reduce nicotine distribution to brain has been proposed as a therapeutic approach to treat nicotine addiction (the basis of tobacco use disorder). A series of monoclonal antibodies with high affinity for nicotine (nic• mAbs) was isolated from B-cells of vaccinated smokers. Genes encoding 32 unique nicotine binding antibodies were cloned, and the mAbs expressed and tested by surface plasmon resonance to determine their affinity for S-(-)-nicotine. The highest affinity nic•mAbs had binding affinity constants (KD) between 5 and 67 nM. The 4 highest affinity nic•mAbs were selected to undergo addnl. secondary screening for antigen-specificity, protein properties (including aggregation and stability), and functional in vivo studies to evaluate their capacity for reducing nicotine distribution to brain in rats. The 2 most potent nic • in single-dose nicotine pharmacokinetic experiments were further tested in a dose-response in vivo study. The most potent lead, ATI-1013, was selected as the lead candidate based on the results of these studies. Pretreatment with 40 and 80 mg/kg ATI-1013 reduced brain nicotine levels by 56 and 95%, resp., in a repeated nicotine dosing experiment simulating very heavy smoking. Nicotine self-administration was also significantly reduced in rats treated with ATI-1013. A pilot rat 30-day repeat-dose toxicol. study (4x200mg/kg ATI-1013) in the presence of nicotine indicated no drug-related safety concerns. These data provide evidence that ATI-1013 could be a potential therapy for the treatment of nicotine addiction.

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, Synthetic Route of 375815-87-5.

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

Carson, Kristin V. published the artcileCurrent and emerging pharmacotherapeutic options for smoking cessation, Application In Synthesis of 375815-87-5, the publication is Substance Abuse: Research and Treatment (2013), 85-105, database is CAplus and MEDLINE.

A review. Tobacco smoking remains the single most preventable cause of morbidity and mortality in developed countries and poses a significant threat across developing countries where tobacco use prevalence is increasing. Nicotine dependence is a chronic disease often requiring multiple attempts to quit; repeated interventions with pharmacotherapeutic aids have become more popular as part of cessation therapies. First-line medications of known efficacy in the general population include varenicline tartrate, bupropion hydrochloride, nicotine replacement therapy products, or a combination thereof. However, less is known about the use of these products in marginalized groups such as the indigenous, those with mental illnesses, youth and pregnant or breastfeeding women. Despite the efficacy and safety of these first line pharmacotherapies, many smokers continue to relapse and alternative pharmacotherapies and cessation options are required. Thus, the aim of this review is to summarize the existing and developing pharmacotherapeutic and other options for smoking cessation, to identify gaps in current clin. practice, and to provide recommendations for future evaluations and research.

Substance Abuse: Research and Treatment 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

Benet, Leslie Z. published the artcileBDDCS Applied to Over 900 Drugs, Category: quinoxaline, the publication is AAPS Journal (2011), 13(4), 519-547, database is CAplus and MEDLINE.

Here, we compile the Biopharmaceutics Drug Disposition Classification System (BDDCS) classification for 927 drugs, which include 30 active metabolites. Of the 897 parent drugs, 78.8% (707) are administered orally. Where the lowest measured solubility is found, this value is reported for 72.7% (513) of these orally administered drugs and a dose number is recorded. The measured values are reported for percent excreted unchanged in urine, LogP, and LogD _7.4 when available. For all 927 compounds, the in silico parameters for predicted Log solubility in water, calculated LogP, polar surface area, and the number of hydrogen bond acceptors and hydrogen bond donors for the active moiety are also provided, thereby allowing comparison analyses for both in silico and exptl. measured values. We discuss the potential use of BDDCS to estimate the disposition characteristics of novel chems. (new mol. entities) in the early stages of drug discovery and development. Transporter effects in the intestine and the liver are not clin. relevant for BDDCS class 1 drugs, but potentially can have a high impact for class 2 (efflux in the gut, and efflux and uptake in the liver) and class 3 (uptake and efflux in both gut and liver) drugs. A combination of high dose and low solubility is likely to cause BDDCS class 4 to be underpopulated in terms of approved drugs (N = 53 compared with over 200 each in classes 1-3). The influence of several measured and in silico parameters in the process of BDDCS category assignment is discussed in detail.

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 C17H19N3O6, Category: quinoxaline.

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

Jutkiewicz, Emily M. published the artcilePatterns of nicotinic receptor antagonism: nicotine discrimination studies, Recommanded Product: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, the publication is Journal of Pharmacology and Experimental Therapeutics (2011), 339(1), 194-202, database is CAplus and MEDLINE.

Evaluation of the discriminative stimulus effects of drugs is a useful procedure for identification of receptor mediation of in vivo drug effects. This assay can be enhanced when the stimulus effects of different doses of agonist are evaluated. In the present study, rats were trained to discriminate small or large doses of nicotine from saline, and interactions of these effects with nicotinic receptor antagonists and partial agonists were determined The insurmountable nicotine antagonist mecamylamine blocked both the discriminative stimulus and response rate-reducing effects of nicotine but was less effective against the large dose of nicotine. The α4β2*-selective, competitive antagonist dihydro-β-erythroiodine (DHβE) antagonized the discriminative stimulus effects of both doses but was less effective against the larger training dose of nicotine. Schild analyses of DHβE suggested that different nicotinic receptor populations may be mediating the stimulus effects of large and small doses of nicotine. This suggestion was supported by observations that the discriminative stimulus effects of the partial agonist cytisine were more like those of the large dose than of the small dose of nicotine and that cytisine antagonized the effects of only the small nicotine dose. Varenicline produced nicotine-like effects in both training dose groups but reduced the discriminative stimulus effects of intermediate doses of nicotine in the group trained to the small dose of nicotine. Overall, these results suggest that small doses of nicotine produce their stimulus effects via α4β2* nicotine receptors, whereas larger doses of nicotine recruit addnl. nicotine receptor subtypes, as revealed by drug discrimination assays in rats.

Journal of Pharmacology and Experimental 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, 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

Ji, Yining published the artcileInnate C-H trifluoromethylation of heterocycles, HPLC of Formula: 375815-87-5, the publication is Proceedings of the National Academy of Sciences of the United States of America (2011), 108(35), 14411-14415, S14411/1-S14411/166, database is CAplus and MEDLINE.

Direct methods for the trifluoromethylation of heteroaromatic systems are in extremely high demand in nearly every sector of chem. industry. Here the authors report the discovery of a general procedure using a bench-top stable trifluoromethyl radical source that functions broadly on a variety of electron deficient and rich heteroaromatic systems and demonstrates high functional group tolerance. This C-H trifluoromethylation protocol is operationally simple (avoids gaseous CF₃I), scalable, proceeds at ambient temperature, can be used directly on unprotected mols., and is demonstrated to proceed at the innately reactive positions of the substrate. The unique and orthogonal reactivity of the trifluoromethyl radical relative to aryl radicals has also been investigated on both a complex natural product and a pharmaceutical agent. Finally, preliminary data suggest that the regioselectivity of C-H trifluoromethylation can be fine-tuned simply by judicious solvent choice. The target compounds thus formed included trifluoromethyl Chantix [varencline 7,8,9,10-tetrahydro-6,10-methano-6H-pyrazino[2,3-h][3]benzazepine].

Proceedings of the National Academy of Sciences of the United States of America 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