Day: December 6, 2022

Chen, Jinfeng published the artcileCo-amorphous systems using epigallocatechin-3-gallate as a co-former: Stability, in vitro dissolution, in vivo bioavailability and underlying molecular mechanisms, Safety of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is epigallocatechin 3 gallate stability dissolution bioavailability mol mechanism; Co-amorphous systems; Co-former; Epigallocatechin-3-gallate; Molecular mechanisms; Nifedipine; Non-sink dissolution; Pharmacokinetic; Simvastatin; Stability.

Co-amorphous strategy has been extensively investigated to improve the dissolution of hydrophobic drugs. Here, epigallocatechin-3-gallate (EGCG) was exploited as a co-former in co-amorphous systems based on its unique structure including Ph rings, phenolic hydroxyl groups and the galloyl moiety. Two model BCS class II drugs, simvastatin (SIM) and nifedipine (NIF), were selected to be co-amorphized with EGCG. All drug-EGCG systems at three molar ratios became amorphous by the means of spray drying and showed high phys. stable either under dry condition and 75 % RH at 40 °C or under dry conditions at 25 °C. The optimal feed molar ratios of both EGCG based co-amorphous systems fabricated were determined to be three, under which the significant increases were obtained in the maximum apparent concentrations of 4.90-fold for SIM at 1 h and 106.03-fold for NIF at 0.25 h compared to crystalline drugs by non-sink dissolution studies. The underlying mol. mechanisms of two co-amorphous systems formation were involved in mol. miscibility, hydrogen bonds and π-π stacking interactions unraveled by means of DSC, FTIR and mol. dynamics simulations. More to the point, oral pharmacokinetic studies in rats demonstrated that co-amorphous SIM-EGCG and NIF-EGCG systems at 1:3 have a significant increase in Cmax of 1.81- and 5.69-fold, and AUC 0-24h of 1.62- and 4.57-fold compared with those of corresponding crystalline drugs, resp. In conclusion, EGCG is proved to be a promising co-former in co-amorphous systems.

European Journal of Pharmaceutics and Biopharmaceutics published new progress about Bioavailability. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Safety of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

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

Wang, Hao published the artcileTakeda G Protein-Coupled Receptor 5 Modulates Depression-like Behaviors via Hippocampal CA3 Pyramidal Neurons Afferent to Dorsolateral Septum, COA of Formula: C17H18N2O6, the main research area is TGR depression behavior hippocampal CA pyramidal neuron dorsolateral septum; Depression; Dorsolateral septum; GABAergic neuron; Hippocampus; Pyramidal neuron; Takeda G protein–coupled receptor 5.

Takeda G protein-coupled receptor 5 (TGR5) is recognized as a promising target for type 2 diabetes and metabolic syndrome; its expression has been demonstrated in the brain and is thought to be neuroprotective. Here, we hypothesize that dysfunction of central TGR5 may contribute to the pathogenesis of depression. In well-established chronic social defeat stress (CSDS) and chronic restraint stress (CRS) models of depression, we investigated the functional roles of TGR5 in CA3 pyramidal neurons (PyNs) and underlying mechanisms of the neuronal circuit in depression (for in vivo studies, n = 10; for in vitro studies, n = 5-10) using fiber photometry; optogenetic, chemogenetic, pharmacol., and mol. profiling techniques; and behavioral tests. Both CSDS and CRS most significantly reduced TGR5 expression of hippocampal CA3 PyNs. Genetic overexpression of TGR5 in CA3 PyNs or intra-CA3 infusion of INT-777, a specific agonist, protected against CSDS and CRS, exerting significant antidepressant-like effects that were mediated via CA3 PyN activation. Conversely, genetic knockout or TGR5 knockdown in CA3 facilitated stress-induced depression-like behaviors. Re-expression of TGR5 in CA3 PyNs rather than infusion of INT-777 significantly improved depression-like behaviors in Tgr5 knockout mice exposed to CSDS or CRS. Silencing and stimulation of CA3 PyNs→ somatostatin-GABAergic (gamma-aminobutyric acidergic) neurons of the dorsolateral septum circuit bidirectionally regulated depression-like behaviors, and blockade of this circuit abrogated the antidepressant-like effects from TGR5 activation of CA3 PyNs. These findings indicate that TGR5 can regulate depression via CA3 PyNs→somatostatin-GABAergic neurons of dorsolateral septum transmission, suggesting that TGR5 could be a novel target for developing antidepressants.

Biological Psychiatry published new progress about Antidepressants. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, COA of Formula: C17H18N2O6.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Kumar, Santosh B. published the artcileCombined anticonvulsant effect of nifedipine and pentazocine in experimentally induced convulsions by electro convulsometer in mice and rats, COA of Formula: C17H18N2O6, the main research area is nifedipine pentazocine anticonvulsant convulsion.

The present study aimed to investigate the combined anticonvulsant effect of nifedipine (calcium channel blocker) and pentazocine (opioid analgesic) on the duration of convulsions, tonic hind limb extension and recovery in mice and rats. The study was initiated after obtaining ethical approval from the Institutional Animal Ethics Committee (IAEC), Department of Pharmacol., Osmania Medical College, Koti, Hyderabad. The anticonvulsant effect of these drugs were screened using Maximal Electro-Shock (MES) method and animals showing tonic hind limb extension response were divided into groups (six animals per group) in both species. Both mice and rats (6 animals/group) were treated with nifedipine (10 mg/kg), pentazocine (30 mg/kg), a combination of nifedipine (10 mg/kg) and pentazocine (30 mg/kg) and control animals are given distilled water as vehicle. The drug administered by an i.p. route. The data were analyzed using ANOVA and group means were compared with LSD Post Hoc Test. P values < 0.05 were considered as significant. The animals treated with both nifedipine 10 mg/kg and pentazocine 30 mg/kg showed a significant reduction in the duration of convulsions and tonic hind limb extension (THLE) in mice and rats as compared to other groups. The results obtained in this study provide supporting pharmacol. evidence of efficacy, the possible potential benefit of combining nifedipine with pentazocine in epilepsy. International Journal of Pharmaceutical Sciences and Research published new progress about Anticonvulsants. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, COA of Formula: C17H18N2O6.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Brueggeman, Leo published the artcileDrug repositioning in epilepsy reveals novel antiseizure candidates, SDS of cas: 21829-25-4, the main research area is epilepsy doxycycline metformin nifedipine pyrantel tartrate repositioning antiseizure.

Epilepsy treatment falls short in ∼30% of cases. A better understanding of epilepsy pathophysiol. can guide rational drug development in this difficult to treat condition. We tested a low-cost, drug-repositioning strategy to identify candidate epilepsy drugs that are already FDA-approved and might be immediately tested in epilepsy patients who require new therapies. Biopsies of spiking and nonspiking hippocampal brain tissue from six patients with unilateral mesial temporal lobe epilepsy were analyzed by RNA-Seq. These profiles were correlated with transcriptomes from cell lines treated with FDA-approved drugs, identifying compounds which were tested for therapeutic efficacy in a zebrafish seizure assay. In spiking vs. nonspiking biopsies, RNA-Seq identified 689 differentially expressed genes, 148 of which were previously cited in articles mentioning seizures or epilepsy. Differentially expressed genes were highly enriched for protein-protein interactions and formed three clusters with associated GO-terms including myelination, protein ubiquitination, and neuronal migration. Among the 184 compounds, a zebrafish seizure model tested the therapeutic efficacy of doxycycline, metformin, nifedipine, and pyrantel tartrate, with metformin, nifedipine, and pyrantel tartrate all showing efficacy. This proof-of-principle anal. suggests our powerful, rapid, cost-effective approach can likely be applied to other hard-to-treat diseases.

Annals of Clinical and Translational Neurology published new progress about Anticonvulsants. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, SDS of cas: 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Kowalska, Magdalena published the artcileAntiepileptic drug tiagabine does not directly target key cardiac ion channels Kv11.1, Nav1.5 and Cav1.2, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is antiepileptic tiagabine target key ion channel Kv Nav Cav; ECG study; cardiac voltage-gated ion channels; molecular modeling; tiagabine.

Tiagabine is an antiepileptic drug used for the treatment of partial seizures in humans. Recently, this drug has been found useful in several non-epileptic conditions, including anxiety, chronic pain and sleep disorders. Since tachycardia-an impairment of cardiac rhythm due to cardiac ion channel dysfunction-is one of the most commonly reported non-neurol. adverse effects of this drug, in the present paper we have undertaken pharmacol. and numerical studies to assess a potential cardiovascular risk associated with the use of tiagabine. A chem. interaction of tiagabine with a model of human voltage-gated ion channels (VGICs) is described using the mol. docking method. The obtained in silico results imply that the adverse effects reported so far in the clin. cardiol. of tiagabine could not be directly attributed to its interactions with VGICs. This is also confirmed by the results from the isolated organ studies (i.e., calcium entry blocking properties test) and in vivo (ECG study) assays of the present research. It was found that tachycardia and other tiagabine-induced cardiac complications are not due to a direct effect of this drug on ventricular depolarization and repolarization.

Molecules published new progress about Anticonvulsants. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Pelat, Michel published the artcileSAR340835, a novel selective Na+/Ca2+ exchanger inhibitor, improves cardiac function and restores sympathovagal balance in heart failure, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is sodium calcium exchanger cardiac arrhythmia heart failure.

In failing hearts, Na+/Ca2+ exchanger (NCX) overactivity contributes to Ca2+ depletion leading to contractile dysfunction. Inhibition of NCX is expected to normalize Ca2+ mishandling, to limit after depolarization-related arrhythmias and to improve cardiac function in heart failure (HF). SAR340835/SAR296968 (NCXi) potently inhibited all NCX isoforms across species with no effect on the native voltage-dependent calcium and sodium currents in vitro. Addnl., it showed in vitro and in vivo anti-arrhythmic properties in several models of early and delayed afterdepolarization-related arrhythmias. Its effect on cardiac function was studied under i.v. infusion at 250 – 750 or 1500 μg/kg/h in dogs either normal or submitted to chronic ventricular pacing at 240 bpm (HF dogs). HF dogs were infused with the reference inotrope dobutamine (10 μg/kg/min i.v.). In normal dogs NCX inhibitor increased cardiac contractility (dP/dtmax), stroke volume (SV) and tended to reduce heart rate (HR). In HF dogs NCX inhibitor significantly and dose-dependently increased SV from the first dose (+28.5%, +48.8%, +62% at 250, 750 and 1500 μg/kg/h resp.) while increasing significantly dP/dtmax only at 1500 (+33%). Furthermore, NCX inhibitor significantly restored sympathovagal balance and spontaneous baroreflex sensitivity (BRS) from the first dose and reduced HR at the highest dose. In HF dogs, dobutamine significantly increased dP/dtmax , SV (+68.8%) but did not change HR, sympathovagal balance nor BRS. Overall, SAR340835 a selective potent NCXi displayed a unique therapeutic profile, combining anti-arrhythmic properties, capacity to restore systolic function, sympathovagal balance and BRS in HF dogs. NCX inhibitors may offer new therapeutic options for acute HF treatment.

Journal of Pharmacology and Experimental Therapeutics published new progress about Antiarrhythmics. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Application of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Manteau, Baptiste published the artcileA General Approach to (Trifluoromethoxy)pyridines: first X-ray Structure Determinations and Quantum Chemistry Studies, Recommanded Product: 2-Chloro-3-(trifluoromethoxy)pyridine, the main research area is general approach synthesis Trifluoromethoxy pyridines crystal structure; ab initio energy profiles rotation trifluoromethoxy methoxy pyridines.

The previously unknown 2-, 3-, and 4-(trifluoromethoxy)pyridines have now become readily accessible by means of an efficient and straightforward large-scale synthesis. Their regioselective functionalization by organometallic methods has been studied and has afforded new and highly important building blocks for life-sciences-oriented research. In addition, the first X-ray crystallog. structure determinations of (trifluoromethoxy)pyridines have been performed. Lowest-energy conformations of (trifluoromethoxy)pyridines and (trifluoromethoxy)pyridinium cations were determined by in silico studies.

European Journal of Organic Chemistry published new progress about Anomeric effect. 1206980-39-3 belongs to class pyridine-derivatives, name is 2-Chloro-3-(trifluoromethoxy)pyridine, and the molecular formula is C6H3ClF3NO, Recommanded Product: 2-Chloro-3-(trifluoromethoxy)pyridine.

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

Lodagekar, Anurag published the artcileCo amorphous valsartan nifedipine system: Preparation, characterization, in vitro and in vivo evaluation, Computed Properties of 21829-25-4, the main research area is valsartan nifedipine amorphous system stability hydrogen bonding; Bioavailability; Co-amorphous delivery system; Dissolution; Nifedipine; Pharmacokinetic; Valsartan.

Co amorphous systems are supersaturated drug delivery systems which offer a basic platform for delivery of multicomponent adducts (combination of more than one active pharmaceutical ingredient (API)) and/or as a fixed dose combination therapy, in addition to their potential to improve the apparent solubility, dissolution rate and ultimately bioavailability of poorly water soluble APIs. In the present work, a new drug-drug co amorphous system namely valsartan-nifedipine was prepared by quench cooling technique. Prepared co amorphous system was characterized for its solid state behavior with the help of Fourier Transform IR spectroscopy (FTIR), Differential Scanning Calorimetry (DSC) and Powder X Ray Diffractometry (PXRD). The optimized co amorphous system was stable for 1 mo when exposed to accelerated stability condition (40 ± 2°C and 75 ± 5% RH). The improved stability of amorphous nifedipine in co amorphous system was attributed to improved miscibility and intra and intermol. non-covalent interactions mainly due to presence of hydrogen bonding between valsartan and nifedipine which was studied by FTIR anal. Co amorphous systems were evaluated by mainly in vitro dissolution and in vivo benefit. In vitro dissolution study showed nearly 5.66 folds and 1.61 folds improvement which was translated to 3.63 and 2.19 times enhancement in vivo Cmax for nifedipine and valsartan resp.

European Journal of Pharmaceutical Sciences published new progress about Amorphous films. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Computed Properties of 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem