Tag: M.W=200-350

Odani, Noritaka published the artcileDetermining the effect of photodegradation on film coated nifedipine tablets with terahertz based coating thickness measurements, Related Products of pyridine-derivatives, the main research area is nifedipine film coating thickness photodegradation TOF MLR; Photostability; Process analytical technology; Tablet coating; Terahertz spectroscopy.

Film coating of nifedipine tablets is commonly performed to reduce photo-degradation The coating thickness of these tablets is a primary dictating factor of photo-stability. Terahertz spectroscopy enables accurate measurement of coating thickness. This study identifies a method to determine an end-point of a photo-protective coating process by using coating thickness measurements from terahertz time of flight spectroscopy (THz-TOF). For this method, nifedipine tablets, at different coating thicknesses, were placed in a photostability chamber. The illumination conditions of the coated tablets were adjusted based on the time duration of these tablets inside the chamber. A multiple linear regression model was developed with the coating thickness estimates from THz-TOF and illumination conditions information to predict the amount of drug remaining after photo-degradation (percent label claim). The prediction error of this model was 1.03% label claim in the range of 88.4-100.6% label claim. According to this model, acceptable levels of photo-protection in illumination conditions of up to approx. 700,000 lx hours was achieved at the end of the coating process (approx. 50 ^fmm coating thickness) performed in this study. These results suggest THz-TOF as a viable process anal. technol. tool for process understanding and end-point determination of a photo-protective coating process.

European Journal of Pharmaceutics and Biopharmaceutics published new progress about Far-IR radiation. 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, Related Products of pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Liu, Bei-Bei published the artcileNS8593 inhibits Ca2+ permeant channels reversing mouse airway smooth muscle contraction, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is NS8593 calcium channel airway smooth muscle allergic asthma; Airway smooth muscle; L-type voltage-dependent Ca(2+) channel; NS8593; Store-operated Ca(2+) entry; Transient receptor potential channel.

This study focused on investigating whether NS8593 reverses airway smooth muscle (ASM) contraction and the underlying mechanism. ASM contraction in mouse tracheal rings and lung slices was measured. Currents mediated by voltage dependent Ca2+ channels (VDCCs) and ACH-activated channels were measured using the whole-cell patch-clamp technique in single tracheal smooth muscle cells (TSMCs). Intracellular Ca2+ level and cell length were measured using an LSM 700 laser confocal microscope and a Zen 2010 software. Mouse respiratory system resistance (Rrs) was assessed using a FlexiVent FX system. High K+ (80 mM K+) and ACH induced ASM contraction in mouse tracheal rings and lung slices, which was partially relaxed by nifedipine (blocker of L-type VDCCs, LVDCCs), YM-58483 (blocker of store-operated Ca2+ entry (SOCE), transient receptor potential C3 (TRPC3) and TRPC5 channels), resp. However, the contraction was completely reversed by NS8593, whereas, slightly relaxed by formoterol. ACH activated inward currents, which displayed linear and reversed around 0 mV, indicating the currents were mediated by non-selective cation channels (NSCCs). Moreover, these currents were blocked by YM-58483. In addition, such currents were abolished by NS8593, implicating that NS8593 inhibits the same channels. Besides, NS8593 inhibited increases of intracellular Ca2+ and the associated cell shortening. Finally, NS8593 inhibited ACH-induced increases of mouse respirator system resistance (Rrs). Our results indicate that NS8593 inhibits LVDCCs and NSCCs, resulting in decreases of intracellular Ca2+ and then leading to ASM relaxation. These data suggest that NS8593 might be a new bronchodilator.

Life Sciences published new progress about Allergic asthma. 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, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

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

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

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

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

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

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

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

Li, Hao published the artcileCalcium channel blockers reduce severe fever with thrombocytopenia syndrome virus (SFTSV) related fatality, Formula: C17H18N2O6, the main research area is benidipine hydrochloride antiviral agent severe fever thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS), an emerging tick-borne infectious disease caused by a novel phlebovirus (SFTS virus, SFTSV), was listed among the top 10 priority infectious diseases by the World Health Organization due to its high fatality of 12%-50% and possibility of pandemic transmission. Currently, effective anti-SFTSV intervention remains unavailable. Here, by screening a library of FDA-approved drugs, we found that benidipine hydrochloride, a calcium channel blocker (CCB), inhibited SFTSV replication in vitro. Benidipine hydrochloride was revealed to inhibit virus infection through impairing virus internalization and genome replication. Further experiments showed that a broad panel of CCBs, including nifedipine, inhibited SFTSV infection. The anti-SFTSV effect of these two CCBs was further analyzed in a humanized mouse model in which CCB treatment resulted in reduced viral load and decreased fatality rate. Importantly, by performing a retrospective clin. investigation on a large cohort of 2087 SFTS patients, we revealed that nifedipine administration enhanced virus clearance, improved clin. recovery, and remarkably reduced the case fatality rate by >5-fold. These findings are highly valuable for developing potential host-oriented therapeutics for SFTS and other lethal acute viral infections known to be inhibited by CCBs in vitro.

Cell Research published new progress about Antiviral agents. 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, Formula: C17H18N2O6.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem