Category: 72509-76-3

Koerber, Thomas published the artcileSystematic differences in the relaxation stretching of polar molecular liquids probed by dielectric vs magnetic resonance and photon correlation spectroscopy, Product Details of C18H19Cl2NO4, the main research area is relaxation stretching polar liquid NMR dielec photon correlation spectroscopy.

Relaxation spectra of mol. glass formers devoid of secondary relaxation maxima, as measured by dielec. spectroscopy (DS), NMR relaxometry, photon correlation spectroscopy (PCS), and Fabry-Perot interferometry, are quant. compared in terms of the Kohlrausch stretching parameter βK. For a reliable estimate of βK, the excess wing contribution has to be included in the spectral anal. The relaxation stretching probed by PCS and NMR varies only weakly among the liquids (βK = 0.58 ± 0.06). It is similar to that found in DS, provided that the liquid is sufficiently nonpolar (relaxation strength Δε≲6). For larger strengths, larger βDSK (narrowed relaxation spectra) are found when compared to those reported from NMR and PCS. Frequency-temperature superposition (FTS) holds for PCS and NMR. This is demonstrated by data scaling and, for the few glass formers for which results are available, by the equivalence of the susceptibilities χ′′PCS(ωτ) ∼ χ′′NMR(τ) ∼ χ′′NMR(ω), i.e., measuring at a constant frequency is equivalent to measuring at a constant temperature or constant correlation time. In this context, a plot of the spin-lattice relaxation rate R1(T) as a function of the spin-spin relaxation rate R2(T) is suggested to reveal the stretching parameter without the need to perform frequency-dependent investigations. Dielec., we identify a trend of increasing deviations from FTS with increasing Δε. Depending on the technique and glass former, the relative relaxation strength of the excess wing varies, whereas its exponent appears to be method independent for a given substance. For polar liquids, we discuss possible reasons for the discrepancy between the results from PCS and NMR as compared to those from DS.

Journal of Chemical Physics published new progress about Dielectric loss. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Product Details of C18H19Cl2NO4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Koli, Akshay R. published the artcileOral bioavailability improvement of felodipine using tailored microemulsion: Surface science, ex vivo and in vivo studies, Recommanded Product: 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is felodipine microemulsion delivery capmul Tween polyethylene glycol oral bioavailability; Felodipine; Microemulsion; Oral bioavailability; Pharmacokinetic studies; Surface science.

Felodipine is a calcium channel blocker, which shows low oral bioavailability (<15%) owing to poor water solubility and high first pass metabolism The aim of the present investigation was to study the surface science (dynamic surface tension) and characteristics of microemulsion (Capmul MCM, Tween 20 and polyethylene glycol) to enhance the oral bioavailability of felodipine by improving permeability of the drug in the intestine. The paper is the first attempt to study the stability of oil-water interface of microemulsion using bubble tensiometer. The Smix at 2:1 ratio showed the maximum microemulsion area which did not alter in the presence of drug. The microemulsion batch coded Fe-O5-Smix45 (5% Capmul MCM and 45% Smix) was selected based on transmittance (>99%), dilution (stable after 100 times dilution with water), size (15.1 nm), dispersibility (grade A) and thermodn. stability studies. The dynamic surface tension at newly created surface indicate the stability of surfactant film at the oil/water interface. The microemulsion was also stable in the presence of drug and in different buffer phases. The ex vivo intestinal permeability studies showed significant increase in the microemulsion permeation (74.1% after 1 h) in comparison to the felodipine suspension (16.9% after 1 h). The in vivo pharmacokinetic parameters in the rat model confirmed the improvement in oral bioavailability with microemulsion (relative bioavailability = 21.9) in comparison to the felodipine suspension, due to high surface area of oil droplets and its lymphatic uptake via transcellular route. In conclusion, the stable microemulsion offers a promising approach to improve the oral bioavailability of felodipine which can help to reduce the dose and its associated side effects.

International Journal of Pharmaceutics (Amsterdam, Netherlands) published new progress about Digestive tract. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Recommanded Product: 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Huang, Jessica published the artcileAngiotensin axis antagonists increase the incidence of haemodynamic instability in dihydropyridine calcium channel blocker poisoning, Quality Control of 72509-76-3, the main research area is dihydropyridine calcium channel blocker angiotensin antagonist haemodynamic bsu; Angiotensin II receptor blockers; amlodipine; angiotensin converting enzyme inhibitors; overdose; toxicity.

Context Amlodipine, a dihydropyridine calcium channel blocker (CCB), is the leading cause of cardiovascular drug-related overdose deaths in the USA. In contrast, angiotensin-II receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) cause minimal toxicity in overdose. ACEIs/ARBs are often combined with dihydropyridines in hypertension treatment. Co-ingested ARBs/ACEIs may significantly contribute to the toxicity of dihydropyridine, but this has not been investigated. Objective To investigate the clin. outcomes from dihydropyridine overdoses with ARBs/ACEIs vs. dihydropyridine overdoses alone. Methods This was a retrospective study of patients reported to the New South Wales Poisons Information Center (NSW PIC) and 3 toxicol. units (Jan 2016 to Jun 2019) in Australia. Patients >14 years who took an overdose of dihydropyridines (amlodipine, felodipine, lercanidipine, nifedipine) were included. Concurrent overdoses with non-dihydropyridine CCBs, alpha-blockers and beta-blockers were excluded. Patient demographics, drugs exposure details, serial vital signs, treatments and outcome were collected.Results There were 100 patients. 68 took mixed overdoses of dihydropyridines with ARBs/ACEIs and 32 took single overdoses of dihydropyridines without ARBs/ACEIs. The mixed group had lower median nadir mean arterial pressures (62 vs 75 mmHg, p < 0.001), more frequently had hypotension (OR 4.5, 95%CI: 1.7-11.9) or bradycardia (OR 8.8, 95%CI: 1.1-70). Multivariable anal. indicated the mixed overdoses had an 11.5 mmHg (95%CI: 4.9-18.1) lower min. systolic blood pressure (SBP) compared with the single group; other factors associated with a lower min. SBP were higher doses [2.3 mmHg (95%CI: 1.1-3.5) lower per 10 defined daily doses] and younger age [2.2 mmHg (95%CI: 0.3-4.2) higher per decade]. A larger proportion of the mixed ingestion group received i.v. fluids (OR 5.7, 95%CI: 1.8-18.6) and antidotes and/or vasopressors (OR 2.9, 95%CI: 1.004-8.6). Conclusion Combined overdoses of dihydropyridines with ARBs/ACEIs caused more significant hypotension and required more haemodynamic support than overdoses of dihydropyridines alone. Clinical Toxicology published new progress about Abdominal pain. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Quality Control of 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Li, Yuanliang published the artcileZearalenone exposure mediated hepatotoxicity via mitochondrial apoptotic and autophagy pathways: Associated with gut microbiome and metabolites, Category: pyridine-derivatives, the main research area is Lactococcus hepatotoxicity zearalenone mitochondria apoptosis autophagy hepatocyte gut microbiota; Gut microbiome; Hepatotoxicity; Metabolomics; Zearalenone.

Zearalenone (ZEN), a mycotoxin is frequently detected in different food products and has been widely studied for its toxicity. However, the underlying mechanisms of hepatotoxic effects, relationship between gut microbiome and liver metabolite mediated hepatotoxicity mechanisms induced by ZEN are still not clear. Here, we reported that the different microscopic changes like swelling of hepatocyte, disorganization of hepatocytes and extensive vacuolar degeneration were observed, and the mitochondrial functions decreased in exposed mice. Results exhibited up-regulation in expression of signals of apoptosis and autophagy in liver of treated mice via mitochondrial apoptotic and autophagy pathway (Beclin1/p62). The diversity of gut microbiome decreased and the values of various microbiome altered in treated mice, including 5 phyla (Chloroflexi, Sva0485, Methylomirabilota, MBNT15 and Kryptonia) and genera (Frankia, Lactococcus, Anaerolinea, Halomonas and Sh765B-TzT-35) significantly changed. Liver metabolism showed that the concentrations of 91 metabolite including lipids and lipid like mols. were significantly changed. The values of phosphatidylcholine, 2-Lysophosphatidylcholine and phosphatidate concentrations suggestive of abnormal glycerophosphate metabolism pathway were significantly increased in mice due to exposure to ZEN. In conclusion, the findings suggest that the disorders in gut microbiome and liver metabolites due to exposure to ZEN in mice may affect the liver.

Toxicology published new progress about Actinobacteria. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Category: pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Kishor, S. published the artcileA complete guide on the pharmacologic and pharmacotherapeutic aspects of calcium channel blockers: an extensive review, Application In Synthesis of 72509-76-3, the main research area is review pharmacol pharmacokinetic pharmacotherapeutic calcium channel blocker.

The calcium channel blockers, a diverse group of cardiovascular drugs, exert their action by inhibiting the L-type calcium channels and cause vasodilatation in the heart and the smooth muscles. They also block the action potential at the SA and AV node, thus prolonging the duration of the action potential (Verapamil and Diltiazem). Although, the calcium channel blockers have the same anti-hypertensive actions, they have a vast difference in their pharmacol. actions, pharmacokinetic profile, and adverse reactions. The main aim was to review, compare, and understand the complete pharmacol. profile of all the calcium channel blockers and understand their place in pharmacotherapy. Numerous articles and studies showed that amlodipine remains to be the safe and effective drug of choice in chronic hypertension due to its slow, prolonged duration of action and lesser incidence of reflux tachycardia. The newer calcium channel blockers, although similar to amlodipine in blood pressure lowering effect, have several pharmacol. advantages. Felodipine was found to be slightly better than amlodipine in the treatment of ischemia/angina due to its high pre-load reducing the effect. Lercanidipine was found to be a better reno-protective agent than amlodipine due to its actions in the kidney. Benidipine was found to be an excellent, anti-atherosclerotic, and reno-protective agent. The incidence of baroreceptor activation and pedal edema was also found to be lower in the newer calcium channel blockers. Hence, the new generation calcium channel blockers could be preferred for various cardiovascular problems.

International Journal of Pharmaceutical Sciences and Research published new progress about Angina pectoris. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Application In Synthesis of 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Brinkmann, Joscha published the artcilePC-SAFT Modeling of Phase Equilibria Relevant for Lipid-Based Drug Delivery Systems, Application In Synthesis of 72509-76-3, the main research area is PC SAFT model phase equilibrium lipid drug delivery system; API solubility prediction.

In this work we investigated the solubilities of 10 active pharmaceutical ingredients (APIs), namely, fenofibrate, ibuprofen, cinnarizine, carbamazepine, indomethacin, naproxen, griseofulvin, glibenclamide, felodipine, and praziquantel in the pharmaceutically relevant excipients tricaprylin, Lauroglycol FCC, Capryol 90, Kolliphor TPGS, ethanol, and monolaurin. API solubilities were either determined gravimetrically, with high-performance liquid chromatog., or with differential scanning calorimetry. Mutual solubilities in the three possible mixtures out of Kolliphor TPGS, tricaprylin, and carbitol as well as the vapor sorption of ethanol in tricaprylin were determined exptl. The Perturbed-Chain Statistical Associating Fluid Theory (PC-SAFT) pure-component parameters for seven APIs were determined via fitting to vapor pressures and liquid densities or to solubilities in organic solvents. In total, 80 binary interaction parameters were fitted to the investigated binary mixtures They can be used in the future to improve the accuracy of lipid-based drug delivery systems in-silico screenings with PC-SAFT.

Journal of Chemical & Engineering Data published new progress about Binary mixtures. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Application In Synthesis of 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Loza-Huerta, Arlet published the artcileThallium-sensitive fluorescent assay reveals loperamide as a new inhibitor of the potassium channel Kv10.1, HPLC of Formula: 72509-76-3, the main research area is thallium loperamide potassium channel inhibitor; Electrophysiology; Kv10.1 potassium channel; Oncogenic channel; Thallium-sensitive fluorescent assay.

Ion channels have been proposed as therapeutic targets for different types of malignancies. One of the most studied ion channels in cancer is the voltage-gated potassium channel ether-a-́go-go 1 or Kv10.1. Various studies have shown that Kv10.1 expression induces the proliferation of several cancer cell lines and in vivo tumor models, while blocking or silencing inhibits proliferation. Kv10.1 is a promising target for drug discovery modulators that could be used in cancer treatment. This work aimed to screen for new Kv10.1 channel modulators using a thallium influx-based assay. Pharmacol. effects of small mols. on Kv10.1 channel activity were studied using a thallium-based fluorescent assay and patch-clamp electrophysiol. recordings, both performed in HEK293 stably expressing the human Kv10.1 potassium channel. In thallium-sensitive fluorescent assays, we found that the small mols. loperamide and amitriptyline exert a potent inhibition on the activity of the oncogenic potassium channel Kv10.1. These results were confirmed by electrophysiol. recordings, which showed that loperamide and amitriptyline decreased the amplitude of Kv10.1 currents in a dose-dependent manner. Both drugs could be promising tools for further studies. Thallium-sensitive fluorescent assay represents a reliable methodol. tool for the primary screening of different mols. with potential activity on Kv10.1 channels or other K+ channels.

Pharmacological Reports published new progress about Antitumor agents. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, HPLC of Formula: 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Federico, Leonardo Bruno published the artcileIdentification of known drugs as potential SARS-CoV-2 Mpro inhibitors using ligand- and structure-based virtual screening, COA of Formula: C18H19Cl2NO4, the main research area is SARSCoV2 mpro inhibitor ligand screening; COVID-19; SARS-CoV-2; drug repositioning; ligand-based drug discovery; main-protease (Mpro); structure-based drug discovery.

Background: The new coronavirus pandemic has had a significant impact worldwide, and therapeutic treatment for this viral infection is being strongly pursued. Efforts have been undertaken by medicinal chemists to discover mols. or known drugs that may be effective in COVID-19 treatment – in particular, targeting the main protease (Mpro) of the virus. Materials & methods: We have employed an innovative strategy – application of ligand- and structure-based virtual screening – using a special compilation of an approved and diverse set of SARS-CoV-2 crystallog. complexes that was recently published. Results and conclusion: We identified seven drugs with different original indications that might act as potential Mpro inhibitors and may be preferable to other drugs that have been repurposed. These drugs will be exptl. tested to confirm their potential Mpro inhibition and thus their effectiveness against COVID-19.

Future Medicinal Chemistry published new progress about Antiviral agents. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, COA of Formula: C18H19Cl2NO4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Yamada, Makiko published the artcileCritical impact of drug-drug interactions via intestinal CYP3A in the risk assessment of weak perpetrators using physiologically based pharmacokinetic models, Formula: C18H19Cl2NO4, the main research area is drug interaction intestinal CYP3A physiol pharmacokinetic model.

A great deal of effort has been being made to improve the accuracy of the prediction of drug-drug interactions (DDIs). In this study, we addressed CYP3A-mediated weak DDIs, in which a relatively high false prediction rate was pointed out. We selected 17 orally administered drugs that have been reported to alter area under the curve (AUC) of midazolam, a typical CYP3A substrate, 0.84-1.47 times. For weak CYP3A perpetrators, the predicted AUC ratio mainly depends on intestinal DDIs rather than hepatic DDIs because the drug concentration in the enterocytes is higher. Thus, DDI prediction using simulated concentration-time profiles in each segment of the digestive tract was made by physiol. based pharmacokinetic (PBPK) modeling software GastroPlus. Although mechanistic static models tend to overestimate the risk to ensure the safety of patients, some underestimation is reported about PBPK modeling. Our in vitro studies revealed that 16 out of 17 tested drugs exhibited time-dependent inhibition (TDI) of CYP3A, and the subsequent DDI simulation that ignored these TDIs provided false-neg. results. This is considered to be the cause of past underestimation. Inclusion of the DDI parameters of all the known DDI mechanisms, reversible inhibition, TDI, and induction, which have opposite effects on midazolam AUC, to PBPK model was successful in improving predictability of the DDI without increasing false-neg. prediction as trade-off. This comprehensive model-based anal. suggests the importance of the intestine in assessing weak DDIs via CYP3A and the usefulness of PBPK in predicting intestinal DDIs. Although drug-drug interaction (DDI) prediction has been extensively performed previously, the accuracy of prediction for weak interactions via CYP3A has not been thoroughly investigated. In this study, we simulate DDIs considering drug concentration-time profile in the enterocytes and discuss the importance and the predictability of intestinal DDIs about weak CYP3A perpetrators.

Drug Metabolism & Disposition published new progress about Drug interactions. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Formula: C18H19Cl2NO4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Garcia-Marin, Luis M. published the artcileLarge-scale genetic investigation reveals genetic liability to multiple complex traits influencing a higher risk of ADHD, Safety of 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is genetic liability attention deficit hyperactivity disorder child adult.

Attention Deficit-Hyperactivity Disorder (ADHD) is a complex psychiatric and neurodevelopmental disorder that develops during childhood and spans into adulthood. ADHD’s etiol. is complex, and evidence about its cause and risk factors is limited. We leveraged genetic data from genome-wide association studies (GWAS) and performed latent causal variable analyses using a hypothesis-free approach to infer causal associations between 1387 complex traits and ADHD. We identified 37 inferred potential causal associations with ADHD risk. Our results reveal that genetic variants associated with iron deficiency anemia (ICD10), obesity, type 2 diabetes, synovitis and tenosynovitis (ICD10), polyarthritis (ICD10), neck or shoulder pain, and substance use in adults display partial genetic causality on ADHD risk in children. Genetic variants associated with ADHD have a partial genetic causality increasing the risk for chronic obstructive pulmonary disease and carpal tunnel syndrome. Protective factors for ADHD risk included genetic variants associated with the likelihood of participating in socially supportive and interactive activities. Our results show that genetic liability to multiple complex traits influences a higher risk for ADHD, highlighting the potential role of cardiometabolic phenotypes and phys. pain in ADHD’s etiol. These findings have the potential to inform future clin. studies and development of interventions.

Scientific Reports published new progress about Adult, mammalian. 72509-76-3 belongs to class pyridine-derivatives, name is 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C18H19Cl2NO4, Safety of 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem