Tag: M.W=350-400

Goktalay, Tugba published the artcileVarenicline disrupts prepulse inhibition only in high-inhibitory rats, Category: quinoxaline, the publication is Progress in Neuro-Psychopharmacology & Biological Psychiatry (2014), 54-60, database is CAplus and MEDLINE.

Varenicline, a widely used smoking cessation drug, has partial agonistic activity at α4β2 nicotinic receptors, and full agonistic activity at α7 nicotinic receptors. Thus it may interact with cognitive processes and may alleviate some of the cognitive disturbances observed in psychotic illnesses such as schizophrenia. We aimed to test the effects of varenicline on sensorimotor gating functioning, which is crucial for normal cognitive processes, especially for the integration of sensory and cognitive information processing and the execution of appropriate motor responses. Prepulse inhibition (PPI) of the acoustic startle reflex was used to test the sensorimotor gating functioning. First, the effects of varenicline and nicotine on rats having high or low baseline PPI levels were evaluated; then, varenicline was applied prior to apomorphine (0.5 mg/kg), and MK-801 (0.15 mg/kg), which are used as comparative models of PPI disruption. Varenicline (0.5-3 mg/kg) did not change PPI when given alone in naive animals. When rats were selected according to their baseline PPI values, varenicline (1 mg/kg) significantly decreased PPI in high-inhibitory (HI) but not in low-inhibitory (LI) rats. Nicotine (1 mg/kg; tartrate salt) produced a similar activity in LI and HI groups. In combination experiments, varenicline did not reverse either apomorphine or the MK-801-induced disruption of PPI. These results demonstrate that the effects of both varenicline and nicotine on sensorimotor gating are influenced by the baseline PPI levels. Moreover, varenicline has no effect on apomorphine or the MK-801-induced disruption of PPI.

Progress in Neuro-Psychopharmacology & Biological Psychiatry 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

Topczewski, Joseph J. published the artcilePalladium-catalysed transannular C-H functionalization of alicyclic amines, SDS of cas: 375815-87-5, the publication is Nature (London, United Kingdom) (2016), 531(7593), 220-224, database is CAplus and MEDLINE.

Discovering pharmaceutical candidates is a resource-intensive enterprise that frequently requires the parallel synthesis of hundreds or even thousands of mols. C-H bonds are present in almost all pharmaceutical agents. Consequently, the development of selective, rapid and efficient methods for converting these bonds into new chem. entities has the potential to streamline pharmaceutical development. Saturated nitrogen-containing heterocycles (alicyclic amines) feature prominently in pharmaceuticals, such as treatments for depression (paroxetine, amitifadine), diabetes (gliclazide), leukemia (alvocidib), schizophrenia (risperidone, belaperidone), malaria (mefloquine) and nicotine addiction (cytisine, varenicline). However, existing methods for the C-H functionalization of saturated nitrogen heterocycles, particularly at sites remote to nitrogen, remain extremely limited. Here we report a transannular approach to selectively manipulate the C-H bonds of alicyclic amines at sites remote to nitrogen. Our reaction uses the boat conformation of the substrates to achieve palladium-catalyzed amine-directed conversion of C-H bonds to C-C bonds on various alicyclic amine scaffolds. We demonstrate this approach by synthesizing new derivatives of several bioactive mols., including varenicline.

Nature (London, United Kingdom) 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 C8H6ClF, SDS of cas: 375815-87-5.

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

Sorbera, L. A. published the artcileVarenicline tartrate: aid to smoking cessation nicotinic α₄β₂ partial agonist, Name: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, the publication is Drugs of the Future (2006), 31(2), 117-122, database is CAplus.

A review. Nicotine addiction is one of the most prevalent addictive behaviors worldwide and more than half of the estimated 1.25 billion smokers will die from tobacco-related illness. Tobacco smoking induces and sustains a series of neurochem. events that are mediated via nicotine’s agonist activity at neuronal nicotinic acetylcholine receptors (nAChRs). Current options for smoking cessation include nicotine replacement therapy, which can be effective but does not prevent nAChR activation, nicotine vaccines, which can block nicotine activation but may not improve craving and withdrawal, behavioral treatment and acupuncture, which are not always effective, and pharmacotherapy comprised of substances selectively targeting the action of nicotine. Researchers continue to investigate possible targets for the development of more effective agents to aid in smoking cessation. One promising agent to emerge is the partial α₄β₂ nAChR agonist varenicline tartrate. This 3,5-bicyclic arylpiperidine selectively binds to the α₄β₂ nAChR and exhibits both potent preclin. partial agonist efficacy and safe and effective clin. activity. Varenicline has been submitted for regulatory approval in the U.S. and Europe for smoking cessation.

Drugs of the Future 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 C17H18N3NaO3S, 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

Turner, Jill R. published the artcileParallel Anxiolytic-Like Effects and Upregulation of Neuronal Nicotinic Acetylcholine Receptors Following Chronic Nicotine and Varenicline, Related Products of quinoxaline, the publication is Nicotine & Tobacco Research (2011), 13(1), 41-46, database is CAplus and MEDLINE.

Introduction: Clin. and preclin. studies suggest that regulation of nicotinic acetylcholine receptors (nAChR) maybe involved in the etiol. of withdrawal symptoms. Methods: We evaluated heteromeric nAChR regulation via [³H]epibatidine binding following cessation of chronic nicotine or varenicline treatment. Animals were concurrently tested in the marble-burying test to evaluate treatment-related effects. Results: We found that both nicotine (18 mg/kg/day, free base) and varenicline (1.8 mg/kg/day) chronically administered for 14 days upregulated nAChRs significantly in the cortex, hippocampus, striatum, and thalamus. The duration of upregulation (up to 72 h) was both drug and region specific. In addition to nAChR upregulation, chronic administration of both nicotine and varenicline had anxiolytic-like effects in the marble-burying test. This effect was maintained for 48 h following cessation of varenicline but was absent 24 h following cessation from nicotine. Addnl., marble-burying behavior pos. correlated to the regulation of cortical nAChRs following cessation of either treatment. Conclusions: Varenicline has been shown to be an efficacious smoking cessation aid, with a proposed mechanism of action that includes modulation of dopamine release in reward areas of the brain. Our studies show that varenicline elicits both anxiolytic effects in the marble-burying test as well as region- and time-specific receptor upregulation. These findings suggest receptor upregulation as a mechanism for its efficacy as a smoking cessation therapy.

Nicotine & Tobacco 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 C5H5ClIN, Related Products of quinoxaline.

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

Kocak, Engin published the artcileValidation of spectrophotometric method to quantify varenicline content in tablets, Name: 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, the publication is Asian Journal of Chemistry (2013), 25(4), 1845-1848, database is CAplus.

Varenicline is a nicotinic receptor partial agonist used to treat smoking addiction. The objective of this work was to develop and validate UV-Vis spectrophotometric method for the determination of varenicline in tablets. In this study, 0.01 M phosphate buffer arranged to pH 7 was used to prepare standard stock solutions from varenicline tartrate salt, as well used to dissolve the commercials tablet and synthetic tablet solutions UV-VIS spectrophotometric determination was performed at 319 nm wavelength having no interference coming from matrix components. The developed method was linear within the range 1-100 μg mL^-1. Method validation was performed according to the ICH guideline and the results show that this simple and low cost method is precise, accurate, robust and rugged to be proposed for the routine anal. in quality control laboratories

Asian Journal of 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 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

Chhabra, Pankdeep published the artcileAdverse Event Reporting Patterns of Newly Approved Drugs in the USA in 2006: An Analysis of FDA Adverse Event Reporting System Data, HPLC of Formula: 375815-87-5, the publication is Drug Safety (2013), 36(11), 1117-1123, database is CAplus and MEDLINE.

Background: The Weber effect states that adverse event (AE) reporting tends to increase in the first 2 years after a new drug is placed onto the market, peaks at the end of the second year, and then declines. However, since the Weber effect was originally described, there has been improvement in the communication of safety information and new policies regarding the reporting of AEs by healthcare professionals and consumers, prompting reassessment of the existence of the Weber effect in the current AE reporting scenario. Objectives: To determine the AE reporting patterns for new mol. entity (NME) drugs and biologics approved in 2006 and to examine these patterns for the existence of the Weber effect. Methods: Publicly available FDA Adverse Event Reporting System data were used to assess the AE reporting patterns for a 5-yr period from the drug’s approval date. The total number of annual reports from all sources, based on the report date, was plotted against time (in years). Results: In the period from 2006 to 2011, a total of 91,187 AE reports were submitted for 19 NMEs approved in 2006. The highest number of AE reports were submitted for varenicline tartrate (N = 47,158) and the lowest number for anidulafungin (N = 161). Anidulafungin was reported to have the highest proportion of death reports (36 %) and varenicline tartrate the lowest proportion (1.7 %). The classic Weber pattern was not observed for any of the 19 NMEs approved in 2006. While there was no one predominant pattern of AE report volume, we grouped the drugs into four general categories; the majority of drugs had either a continued increase in reports (Category A 31.6 %) or an N-pattern with reporting reaching an initial peak in year 2 or 3, declining and then beginning to climb again (Category B 42.1 %). Conclusions and relevance: There have been numerous changes in AE reporting, particularly a huge increase in overall annual report volume, since the Weber effect was first reported. Our results suggest that a Weber-type reporting pattern should not be assumed in the design or interpretation of analyses based on AE reports.

Drug Safety 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

Huff, Chelsea A. published the artcilePhotoredox-Catalyzed Hydroxymethylation of Heteroaromatic Bases, Computed Properties of 375815-87-5, the publication is Journal of Organic Chemistry (2016), 81(16), 6980-6987, database is CAplus and MEDLINE.

We report the development of a method for room-temperature C-H hydroxymethylation of heteroarenes. A key enabling advance in this work was achieved by implementing visible light photoredox catalysis that proved to be applicable to many classes of heteroarenes and tolerant of diverse functional groups found in druglike mols.

Journal of Organic 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 C17H19N3O6, Computed Properties of 375815-87-5.

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

Werner, Felix-Martin published the artcileLong-term Administration of Antipsychotic Drugs in Schizophrenia and Influence of Substance and Drug Abuse on the Disease Outcome, Application of 7,8,9,10-Tetrahydro-6H-6,10-methanoazepino[4,5-g]quinoxaline (2R,3R)-2,3-dihydroxysuccinate, the publication is Current Drug Abuse Reviews (2017), 10(1), 19-24, database is CAplus and MEDLINE.

A review. Many schizophrenic patients with a long-term administration of antipsychotic drugs do not regularly adhere to the prescribed pharmacotherapy. Antipsychotic drugs constitute a palliative, but not a curative treatment, and the long-term effect of these drugs is not secure. Patients tend to consume nicotine and alc., as well as some patients consume drugs such as cannabis and amphetamines. The objective of this mini-review is to examine the reasons for the high tendency of schizophrenic patients to consume alc., nicotine and drugs and in addition to suggest measures to reduce the abuse of substances and drugs. The effects of substances such as alc. and nicotine and drugs such as cannabis and amphetamines on the disease outcome will be mentioned. Previous reviews on the psychotic disorders and the pharmacol. treatment were used to examine the effects of substances and drugs on schizophrenic symptoms and to investigate appropriate measures to improve medication adherence and the renouncement of consuming substances and drugs. A possible coherence between the function of single susceptibility genes and the alteration of neurotransmitters is mentioned. The mechanism of action of the most important secondgeneration antipsychotic drugs and their indications are described. The tendency of schizophrenic patients to consume alc. and nicotine and in addition the effect of both substances to possibly worsen psychotic symptoms are pointed out. The effect of nicotinergic agonists to support smoking cessation is described. The different compounds of cannabis, tetrahydrocannabidiol (a psychotomimetic) and cannabidiol (exerts antipsychotic actions), are mentioned. Because a reduced adherence to the pharmacotherapy is frequently combined with the abuse of substances, addnl. drugs, psychoeducation and the administration of long-acting injectable antipsychotic drugs could reduce the abuse of substances and drugs; these strategies could help to maintain the antipsychotic administration. The abuse of drugs and substances might be combined with a reduced adherence to the antipsychotic pharmacotherapy. Drugs and substances might in some cases worsen the psychotic symptoms. Appropriate measures to reduce substance and drug abuse as well as to improve the adherence to the antipsychotic pharmacotherapy are cognitive behavioral therapy, psychoeducation and the administration of long-acting injectable antipsychotic drugs. Some new drugs, for example the cannabis compound cannabidiol that shows antipsychotic properties and β-varenicline, a nicotinergic cholinergic agonist, might be administered when substance abuse (cannabis, nicotine) occurs.

Current Drug Abuse Reviews 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 C8H6ClF3, 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

Broccatelli, Fabio published the artcileBDDCS Class Prediction for New Molecular Entities, COA of Formula: C17H19N3O6, the publication is Molecular Pharmaceutics (2012), 9(3), 570-580, database is CAplus and MEDLINE.

The Biopharmaceutics Drug Disposition Classification System (BDDCS) was successfully employed for predicting drug-drug interactions (DDIs) with respect to drug metabolizing enzymes (DMEs), drug transporters and their interplay. The major assumption of BDDCS is that the extent of metabolism (EoM) predicts high vs. low intestinal permeability rate, and vice versa, at least when uptake transporters or paracellular transport is not involved. We recently published a collection of over 900 marketed drugs classified for BDDCS. We suggest that a reliable model for predicting BDDCS class, integrated with in vitro assays, could anticipate disposition and potential DDIs of new mol. entities (NMEs). Here we describe a computational procedure for predicting BDDCS class from mol. structures. The model was trained on a set of 300 oral drugs, and validated on an external set of 379 oral drugs, using 17 descriptors calculated or derived from the VolSurf+ software. For each mol., a probability of BDDCS class membership was given, based on predicted EoM, FDA solubility (FDAS) and their confidence scores. The accuracy in predicting FDAS was 78% in training and 77% in validation, while for EoM prediction the accuracy was 82% in training and 79% in external validation. The actual BDDCS class corresponded to the highest ranked calculated class for 55% of the validation mols., and it was within the top two ranked more than 92% of the time. The unbalanced stratification of the data set did not affect the prediction, which showed highest accuracy in predicting classes 2 and 3 with respect to the most populated class 1. For class 4 drugs a general lack of predictability was observed A linear discriminant anal. (LDA) confirming the degree of accuracy for the prediction of the different BDDCS classes is tied to the structure of the data set. This model could routinely be used in early drug discovery to prioritize in vitro tests for NMEs (e.g., affinity to transporters, intestinal metabolism, intestinal absorption and plasma protein binding). We further applied the BDDCS prediction model on a large set of medicinal chem. compounds (over 30,000 chems.). Based on this application, we suggest that solubility, and not permeability, is the major difference between NMEs and drugs. We anticipate that the forecast of BDDCS categories in early drug discovery may lead to a significant R&D cost reduction

Molecular Pharmaceutics 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

Hoffman, Keith B. published the artcileA Pharmacovigilance Signaling System Based on FDA Regulatory Action and Post-Marketing Adverse Event Reports, Category: quinoxaline, the publication is Drug Safety (2016), 39(6), 561-575, database is CAplus and MEDLINE.

Many serious drug adverse events (AEs) only manifest well after regulatory approval. Therefore, the development of signaling methods to use with post-approval AE databases appears vital to comprehensively assess real-world drug safety. However, with millions of potential drug-AE pairs to analyze, the issue of focus is daunting. Our objective was to develop a signaling platform that focuses on AEs with historically demonstrated regulatory interest and to analyze such AEs with a disproportional reporting method that offers broad signal detection and acceptable false-pos. rates. We analyzed over 1500 US FDA regulatory actions (safety communications and drug label changes) from 2008 to 2015 to construct a list of eligible signal AEs. The FDA Adverse Event Reporting System (FAERS) was used to evaluate disproportional reporting rates, constrained by min. case counts and confidence interval limits, of these selected AEs for 109 training drugs. This step led to 45 AEs that appeared to have a low likelihood of being added to a label by FDA, so they were removed from the signal eligible list. We measured disproportional reporting for the final group of eligible AEs on a test group of 29 drugs that were not used in either the eligible list construction or the training steps. In a group of 29 test drugs, our model reduced the number of potential drug-AE signals from 41,834 to 97 and predicted 73 % of individual drug label changes. The model also predicted at least one AE-drug pair label change in 66 % of all the label changes for the test drugs. By concentrating on AE types with already demonstrated interest to FDA, we constructed a signaling system that provided focus regarding drug-AE pairs and suitable accuracy with regard to the issuance of FDA labeling changes. We suggest that focus on historical regulatory actions may increase the utility of pharmacovigilance signaling systems.

Drug Safety 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