Tag: M.W=200-350

Ulivieri, Alessandra published the artcileThyroid hormones regulate cardiac repolarization and QT-interval related gene expression in hiPSC cardiomyocytes, Formula: C17H18N2O6, the main research area is thyroid hormone induced pluripotent stem cardiomyocyte cardiac dysfunction.

Prolongation of cardiac repolarization (QT interval) represents a dangerous and potentially life-threatening elec. event affecting the heart. Thyroid hormones (THs) are critical for cardiac development and heart function. However, little is known about THs influence on ventricular repolarization and controversial effects on QT prolongation are reported. Human iPSC-derived cardiomyocytes (hiPSC-CMs) and multielectrode array (MEA) systems were used to investigate the influence of 3,3′,5-triiodo-L-Thyronine (T3) and 3,3′,5,5′-tetraiodo-L-Thyronine (T4) on corrected Field Potential Duration (FPDc), the in vitro analog of QT interval, and on local extracellular Action Potential Duration (APD). Treatment with high THs doses induces a significant prolongation of both FPDc and APD, with the strongest increase reached after 24 h exposure. Preincubation with reverse T3 (rT3), a specific antagonist for nuclear TH receptor binding, significantly reduces T3 effects on FPDc, suggesting a TRs-mediated transcriptional mechanism. RNA-seq anal. showed significant deregulation in genes involved in cardiac repolarization pathways, including several QT-interval related genes. In conclusion, long-time administration of high THs doses induces FPDc prolongation in hiPSC-CMs probably through the modulation of genes linked to QT-interval regulation. These results open the way to investigate new potential diagnostic biomarkers and specific targeted therapies for cardiac repolarization dysfunctions.

Scientific Reports published new progress about Biomarkers. 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

Held, Katharina published the artcilePharmacological properties of TRPM3 isoforms are determined by the length of the pore loop, Computed Properties of 21829-25-4, the main research area is trpm3 pore loop length pharmacol property; Splice variants TRP channels; TRPM3; nociception.

Background and Purpose : Transient receptor potential melastatin 3 (TRPM3) is a non-selective cation channel that plays a pivotal role in the peripheral nervous system as a transducer of painful heat signals. Alternative splicing gives rise to several TRPM3 variants. The functional consequences of these splice isoforms are poorly understood. Here, the pharmacol. properties of TRPM3 variants arising from alternative splicing in the pore-forming region were compared. Exptl. Approach : Calcium microfluorimetry and patch clamp recordings were used to compare the properties of heterologously expressed TRPM3α1 (long pore variant) and TRPM3α2-α6 (short pore variants). Furthermore, site-directed mutagenesis was done to investigate the influence of the length of the pore loop on the channel function. Key Results : All short pore loop TRPM3α variants (TRPM3α2-α6) were activated by the neurosteroid pregnenolone sulfate (PS) and by nifedipine, whereas the long pore loop variant TRPM3α1 was insensitive to either compound In contrast, TRPM3α1 was robustly activated by clotrimazole, a compound that does not directly activate the short pore variants but potentiates their responses to PS. Clotrimazole-activated TRPM3α1 currents were largely insensitive to established TRPM3α2 antagonists and were only partially inhibited upon activation of the μ opioid receptor. Finally, by creating a set of mutant channels with pore loops of intermediate length, we showed that the length of the pore loop dictates differential channel activation by PS and clotrimazole. Conclusion and Implications : Alternative splicing in the pore-forming region of TRPM3 defines the channel’s pharmacol. properties, which depend critically on the length of the pore-forming loop.

British Journal of Pharmacology published new progress about Cerebellum. 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

Gui, Yue published the artcilePolymorphic selectivity in crystal nucleation, Computed Properties of 21829-25-4, the main research area is polymorphic selectivity crystal nucleation glass forming liquid.

Crystal nucleation rates were measured in the supercooled melts of 2 richly polymorphic glass-forming liquids: 5-Me-2-[(2-nitrophenyl)amino]-3-thiophenecarbonitrile (ROY) and nifedipine (NIF). ROY is known for its crystals of red, orange, and yellow colors and many polymorphs of solved structures. Of the many polymorphs, ON (orange needles) nucleates the fastest with the runner up (Y04) trailing by a factor of 103 when compared under the same mobility-limited condition, while the other unobsd. polymorphs are slower yet by ≥5 orders of magnitude. Of the 6 polymorphs of NIF, γ’ nucleates the fastest, β’ is slower by a factor of 10, and the rest are slower yet by ≥5 decades. In both systems, the faster-nucleating polymorphs are not built from the lowest-energy conformers, while they tend to have higher energies and lower densities and thus greater similarity to the liquid phase by these measures. The temperature ranges of this study covered the glass transition temperature Tg of each system, and no evidence that the nucleation rate is sensitive to the passage of Tg were found. At the lowest temperatures studied, the rates of nucleation and growth are proportional to each other, indicating that a similar kinetic barrier controls both processes. The classical nucleation theory provides an accurate description of the observed nucleation rates if the crystal growth rate is used to describe the kinetic barrier for nucleation. The quant. rates of both nucleation and growth for the competing polymorphs enable prediction of the overall rate of crystallization and its polymorphic outcome. (c) 2022 American Institute of Physics.

Journal of Chemical Physics published new progress about Conformers. 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

Lavado, Giovanna J. published the artcileZebrafish AC50 modelling: (Q)SAR models to predict developmental toxicity in zebrafish embryo, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is Danio developmental toxicity QSAR model; AC(50); Classification; Developmental toxicity; In silico aquatic toxicology; QSAR; Regression; Zebrafish embryo.

Developmental toxicity refers to the occurrence of adverse effects on a developing organism as a consequence of exposure to hazardous chems. The assessment of developmental toxicity has become relevant to the safety assessment process of chems. The zebrafish embryo developmental toxicol. assay is an emerging test used to screen the teratogenic potential of chems. and it is proposed as a promising test to replace teratogenic assays with animals. Supported by the increased availability of data from this test, the developmental toxicity assay with zebrafish has become an interesting endpoint for the in silico modeling. The purpose of this study was to build up quant. structure-activity relationship (QSAR) models. In this work, new in silico models for the evaluation of developmental toxicity were built using a well-defined set of data from the ToxCast Phase I chem. library on the zebrafish embryo. Categorical and continuous QSAR models were built by gradient boosting machine learning and the Monte Carlo technique resp., in accordance with Organization for Economic Co-operation and Development principles and their statistical quality was satisfactory. The classification model reached balanced accuracy 0.89 and Matthews correlation coefficient 0.77 on the test set. The regression model reached correlation coefficient R2 0.70 in external validation and leave-one-out cross-validated Q2 0.73 in internal validation.

Ecotoxicology and Environmental Safety published new progress about Danio rerio. 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

Ito, Daishi published the artcileIdentification of the hypertension drug niflumic acid as a glycine receptor inhibitor, Related Products of pyridine-derivatives, the main research area is hypertension niflumic acid glycine inhibitor.

Glycine is one of the major neurotransmitters in the brainstem and the spinal cord. Glycine binds to and activates glycine receptors (GlyRs), increasing Cl- conductance at postsynaptic sites. This glycinergic synaptic transmission contributes to the generation of respiratory rhythm and motor patterns. Strychnine inhibits GlyR by binding to glycine-binding site, while picrotoxin blocks GlyR by binding to the channel pore. We have previously reported that bath application of strychnine to zebrafish embryos causes bilateral muscle contractions in response to tactile stimulation. To explore the drug-mediated inhibition of GlyRs, we screened a chem. library of ∼1,000 approved drugs and pharmacol. active mols. by observing touch-evoked response of zebrafish embryos in the presence of drugs. We found that exposure of zebrafish embryos to nifedipine (an inhibitor of voltage-gated calcium channel) or niflumic acid (an inhibitor of cyclooxygenase 2) caused bilateral muscle contractions just like strychnine-treated embryos showed. We then assayed strychnine, picrotoxin, nifedipine, and niflumic acid for concentration-dependent inhibition of glycine-mediated currents of GlyRs in oocytes and calculated IC50s. The results indicate that all of them concentration-dependently inhibit GlyR in the order of strychnine > picrotoxin > nifedipine > niflumic acid.

Scientific Reports published new progress about Danio rerio. 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

Lal, Chiman published the artcileFormulation and optimization by applying 32 full factorial design of mucoadhesive microspheres of nifedipine, Formula: C17H18N2O6, the main research area is nifedipine mucoadhesive microsphere drug delivery controlled release formulation.

Objective: The purpose of this research work is to formulate and optimize mucoadhesive microspheres of nifedipine using Carbopol 934P as mucoadhesive and Et cellulose as a carrier polymer for controlling the release of nifedipine. Methods: The emulsion solvent evaporation technique was used for the preparation of microspheres and the 32 full factorial designs were employed for optimization of microspheres. The developed microspheres were characterized for percent yield, entrapment efficiency, particle size, in vitro release study, percent mucoadhesion, surface morphol., and stability study. Results: Evaluating outcomes of preliminary batches indicated that 100 mL volume of processing medium, 5 h stirring time and 2% concentration of emulsifying agent were suitable for spherical, free-flowing microspheres and high percentage drug entrapment efficiency. The optimized batch exhibited 84.35% drug entrapment efficiency, 61.78% mucoadhesion and drug release were also sustained for more than 12 h. SEM study revealed that produced microspheres were spherical in shape. Conclusion: Exptl. responses of the optimized batch have close proximity with the predicted value and stability study of the optimized formulation proved the formulation is stable for a long period of time; hence, it is an excellent alternative over the conventional delivery system.

Asian Journal of Pharmaceutical and Clinical Research published new progress about Dissolution. 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

Okada, Hitomi published the artcileCorrelation between drug dissolution and resistance to water-induced phase separation in solid dispersion formulations revealed by solid-state NMR spectroscopy, Synthetic Route of 21829-25-4, the main research area is pharmaceutical solid dispersion dissolution miscibility hypromellose methacrylic acid copolymer; Dissolution; Drug-polymer interaction; Miscibility; Phase separation; Solid dispersion.

We aimed to elucidate the dissolution mechanism of solid dispersions (SDs) according to the carrier polymers used. Nifedipine (NIF) and polymers dissolved simultaneously from NIF/Eudragit S (EUD-S), NIF/Eudragit L (EUD-L), and NIF/hypromellose (HPMC)/EUD-S spray-dried samples (SPDs). In contrast, NIF dissolved sep. from polymers from NIF/HPMC and NIF/HPMC/EUD-L SPDs due to the formation of an amorphous NIF-rich interface. Solid-state NMR spectroscopy indicated that NIF-EUD interactions were stronger than NIF-HPMC interactions. NIF/HPMC SPD exhibited weak interactions; thus, it failed to inhibit phase separation during the dissolution process and control NIF dissolution The hygroscopicity of SPDs was higher with HPMC mixing and increased substitution ratio of methacrylic acid in EUD. Moreover, solid-state NMR spectroscopy revealed that the NIF-EUD interactions were hindered to a large extent by the absorbed water. During the dissolution process of NIF/HPMC/EUD-L SPD, the introduction of water to the NIF-EUD-L interaction site could induce the phase separation and poor controllability of NIF dissolution Water-induced phase separation should be considered based on mol.-level characterization to obtain SDs with enhanced drug dissolution An investigation of the mol. state change caused by the absorbed water using solid-state NMR spectroscopy will be helpful in understanding the dissolution mechanism of SDs.

International Journal of Pharmaceutics (Amsterdam, Netherlands) published new progress about Dissolution. 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, Synthetic Route of 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Xiong, Zhihui published the artcileFour kinds of tocolytic therapy for preterm delivery: Systematic review and network meta-analysis, Formula: C17H18N2O6, the main research area is meta analysis preterm delivery tocolytic therapy safety; Atosiban; Indomethacin; Nifedipine; Ritodrine; network meta-analysis; preterm delivery; tocolysis.

Meta-anal. of premature birth affects more than 15 million infants, as well as mothers and families around the world. With the relaxation of the two-child policy, the problem of premature birth has become relatively prominent in China. According to statistics, China had a birth population of 15.23 million in 2018, with a considerably large number of premature births. This study aims to evaluate the efficacy and safety of tocolysis in the treatment of preterm delivery, provide clin. evidence for medical staff and promote the self-management of patients with premature births. Four English databases (PubMed, Embase, Cochrane Library and Web of Science) were retrieved by computer, the retrieval time was from the establishment of each database to Nov. 2021, and the randomized controlled trials for the treatment of preterm delivery were screened according to the pre-set natriuretic exclusion criteria. After literature screening, data selection and risk of bias evaluation were independently conducted by two researchers. R 4.1.1 and Stata 17.0 software were used for statistical anal. A total of 44 RCTs were included, including 6939 patients. The results of network meta-anal. reveal that in terms of effectiveness, indomethacin was the most effective intervention measure, followed by nifedipine, and the difference was statistically significant; regarding safety, nifedipine was the safest intervention measure, followed by indomethacin, and the difference was statistically significant; and in respect of adverse reactions, ritodrine had the highest probability, and the difference was statistically significant. Nifedipine may be better for delayed delivery and less likely to produce adverse pregnancy outcomes, followed by indomethacin. Limited by the number and quality of recipient studies, the aforementioned conclusions need to be verified through more high-quality studies. At the same time, the focus should be on patients with twin pregnancy and patients with clin. manifestations of extreme preterm delivery.

Journal of Clinical Pharmacy and Therapeutics published new progress about Drug safety. 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

Maafi, Mounir published the artcilePhotokinetics of Dacarbazine and Nifedipine under polychromatic light irradiation and their application as new reliable actinometers for the ultraviolet range, Application In Synthesis of 21829-25-4, the main research area is photokinetics dacarbazine nifedipine polychromatic light irradiation reliable actinometer UV.

The photokinetic behavior of drugs driven by polychromatic light is an area of pharmaceutics that has not received a lot of attention. Most often, such photokinetic data is treated by thermal kinetic models (i.e., the classical 0th-, 1st- or 2nd-order equations). Such models were not anal. derived from the rate-laws of the photodegradation reactions. Polychromatic light kinetic modeling is hence of importance, as a means to providing adequate toolkits and metrics. This paper aims at proposing two reliable drug-actinometers useful for polychromatic UVA range. The general actinometric methodol. offered here is also useful for any drugs/materials obeying a primary photoprocess where both reactant and photoproduct absorb the incident light, of the AB(1φ)εB≠0 type. The present method has been consolidated by the η-order kinetics. This framework further demonstrated the lamp-specificity of actinometers. Overall, Dacarbazine and Nifedipine photodegradations obeyed η-order kinetics, and stand as effective actinometers that can be recommended for the ICH Q1b photostability testing.

Scientific Reports published new progress about Absorption. 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 In Synthesis of 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Seibertz, Fitzwilliam published the artcileSingle-cell optical action potential measurement in human induced pluripotent stem cell-derived cardiomyocytes, Related Products of pyridine-derivatives, the main research area is singlecell optical action potential human pluripotent stem cell cardiomyocyte.

Conventional intracellular microelectrode techniques to quantify cardiomyocyte electrophysiol. are extremely complex, labor intensive, and typically carried out in low throughput. Rapid and ongoing expansion of induced pluripotent stem cell (iPSC) technol. presents a new standard in cardiovascular research and alternate methods are now necessary to increase throughput of electrophysiol. data at a single cell level. VF2.1Cl is a recently derived voltage sensitive dye which provides a rapid single channel, high magnitude response to fluctuations in membrane potential. It possesses kinetics superior to those of other existing voltage indicators and makes available functional data equivalent to that of traditional microelectrode techniques. Here, we demonstrate simplified, non-invasive action potential characterization in externally paced human iPSC derived cardiomyocytes using a modular and highly affordable photometry system.

Journal of Visualized Experiments published new progress about Absorption. 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