Category: pyridine-derivatives

McPherson, Stephanie published the artcileSmall scale design of experiment investigation of equilibrium solubility in simulated fasted and fed intestinal fluid, Product Details of C18H19Cl2NO4, the main research area is intestinal juice PH ibuprofen valsartan zafirlukast indomethacin solubility; Biopharmaceutical Classification System; Design of Experiment; Fasted State Simulated Intestinal fluid; Fed State Simulated Intestinal Fluid; Orbito; Solubility.

It is widely recognized that drug solubility within the gastrointestinal tract (GIT) differs from values determined in a simple aqueous buffer and to circumvent this problem measurement in biorelevant fluids is determined Biorelevant fluids are complex mixtures of components (sodium taurocholate, lecithin, sodium phosphate, sodium chloride, pancreatin and sodium oleate) at various concentrations and pH levels to provide systems simulating fasted (FaSSIF) or fed (FeSSIF) intestinal media. Design of Experiment (DoE) studies have been applied to investigate FaSSIF and FeSSIF and indicate that a drugs equilibrium solubility varies over orders of magnitude, is influenced by the drug type and individual or combinations of media components, with some of these interactions being drug specific. Although providing great detail on the drug media interactions these studies are resource intensive requiring up to ninety individual experiments for FeSSIF. In this paper a low sample number or reduced DoE system has been investigated by restricting components with minimal solubility impact to a single value and only investigating variations in the concentrations of sodium taurocholate, lecithin, sodium oleate, pH and addnl. in the case of fed media, monoglyceride. This reduces the experiments required to ten (FaSSIF) and nine (FeSSIF). Twelve poorly soluble drugs (Ibuprofen, Valsartan, Zafirlukast, Indomethacin, Fenofibrate, Felodipine, Probucol, Tadalafil, Carvedilol, Aprepitant, Bromocriptine and Itraconazole) were investigated and the results compared to published DoE studies and literature solubility values in human intestinal fluid (HIF), FaSSIF or FeSSIF. The solubility range determined by the reduced DoE is statistically equivalent to the larger scale published DoE results in over eighty five percent of the cases. The reduced DoE range also covers HIF, FaSSIF or FeSSIF literature solubility values. In addition the reduced DoE provides lowest measured solubility values that agree with the published DoE values in ninety percent of the cases. However, the reduced DoE only identified single and in some cases none of the major components influencing solubility in contrast to the larger published DoE studies which identified multiple individual components and component interactions. The identification of significant components within the reduced DoE was also dependent upon the drug and system under investigation. The study demonstrates that the lower exptl. number reduces statistical power of the DoE to resolve the impact of media components on solubility However, in a situation where only the solubility range is required the reduced DoE can provide the desired information, which will be of benefit during in vitro development studies. Further refinements are possible to extend the reduced DoE protocol to improve biorelevance and application into areas such as PBPK modeling.

European Journal of Pharmaceutics and Biopharmaceutics published new progress about Homo sapiens. 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

Salunkhe, Nitin published the artcileSericin Inhibits Devitrification of Amorphous Drugs, HPLC of Formula: 72509-76-3, the main research area is lornoxicam meloxicam felodipine sericin devitrification drug stability; amorphous solid dispersions (ASD); devitrification; dissolution; sericin; solubility.

The purpose of the present investigation was to analyze devitrification of amorphous drugs such as lornoxicam, meloxicam, and felodipine in the presence of sericin. The binary solid dispersions comprising varying mass ratios of drug and sericin were subject to amorphization by spray drying, solvent evaporation, ball milling, and phys. mixing. Further, obtained solid dispersions (SDs) were characterized by HPLC, ATR-FTIR, H1NMR, mol. docking, accelerated stability study at 40°C and 75 ± 2% RH (XRD and DSC), and in vitro dissolution studies. The HPLC anal. indicated no decomposition of the drugs during the spray drying process. From ATR-FTIR, NMR, and mol. docking study, it was revealed that H-bonding played a vital role in amorphous drug stabilization. An excellent devitrification inhibition was observed in case of lornoxicam (SDLS3) and meloxicam (SDMS3) SDs prepared by spray drying. On the other hand, spray-dried SD of felodipine (SDFS3) showed traces of microcrystals. The percent crystallinity of SDLS3, SDMS3, and SDFS3 was found to be 7.4%, 8.23%, and 18.31% resp. indicating adequate amorphization. The dissolution performance of SDLS, SDMS, and SDFS after 3 mo showed > 85% than SDs prepared by other methods. Thus, sericin significantly inhibited crystallization and was responsible for amorphous state stabilization of pharmaceuticals.

AAPS PharmSciTech published new progress about Amorphization. 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

Govender, Rydvikha published the artcileEnabling modular dosage form concepts for individualized multidrug therapy: Expanding the design window for poorly water-soluble drugs, Computed Properties of 72509-76-3, the main research area is multidrug therapy poorly water soluble drug; Amorphous solid dispersions; Flexible combinations; Mass customization; Melt extrusion; Oral drug release; Polypharmacy.

Multidrug dosage forms (aka combination dosage forms, polypills, etc.) create value for patients through reduced pill burdens and simplified administration to improve adherence to therapy. Enhanced flexibility of multidrug dosage forms would provide further opportunities to better match emerging needs for individualized therapy. Through modular dosage form concepts, one approach to satisfy these needs is to adapt multidrug dosage forms to a wider variety of drugs, each with a variety of doses and release profiles. This study investigates and tech. explores design requirements for extending the capability of modular multidrug dosage form concepts towards individualization. This builds on our recent demonstration of independent tailoring of dose and drug release, which is here extended towards poorly water-soluble drugs. The challenging design requirement of carrying higher drug loads in smaller volumes to accommodate multiple drugs at their clin. dose is here met regarding dose and release performance. With a modular concept, we demonstrate high precision (<5% RSD) in dose and release performance of individual modules containing felodipine or naproxen in Kollidon VA64 at both a wide drug loading range (5% weight/weight and 50% weight/weight drug) and a small module size (3.6 mg). In a forward-looking design-based discussion, further requirements are addressed, emphasizing that reproducible individual module performance is predictive of dosage form performance, provided the modules are designed to act independently. Therefore, efforts to incorporate progressively higher drug loads within progressively smaller module volumes will be crucial to extend the design window further towards full flexibility of future dosage forms for individualized multidrug therapy. International Journal of Pharmaceutics (Amsterdam, Netherlands) published new progress about Amorphization. 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, Computed Properties of 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Pajzderska, A. published the artcileNMR relaxometry in an investigation of the kinetics of the recrystallization of a three-phase system, SDS of cas: 72509-76-3, the main research area is polyvinylpyrrolidone nuclear magnetic resonances relaxometry recrystallization three phase system; Amorphization; Felodipine; PVP; Physical mixture; Recrystallization; Relaxometry.

The method of 1H NMR (NMR) relaxometry is applied to investigate the kinetics of the recrystallization of an active pharmaceutical ingredient (felodipine) from the amorphous phase of its phys. mixture with a polymer (polyvinylpyrrolidone, PVP). Comparison of the recrystallization results obtained for amorphous felodipine and its mixtures with PVP shows that the recrystallization process of API is faster in the mixtures and depends on the content of water in the system. The free induction decay (FID) for protons that were detected are composed of three components, and the loss of water from PVP strongly influences the part characterized by the longest spin-spin lattice relaxation time. Anal. of the FID of the phys. mixture indicates that the content of water does not change during the recrystalization process. The study shows that the T11H NMR relaxometry method is very useful for analyzing the composition of a three-phase mixture and the recrystallization process.

International Journal of Pharmaceutics (Amsterdam, Netherlands) published new progress about Amorphization. 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, SDS of cas: 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Haware, Rahul V. published the artcilePhysical properties and solubility studies of Nifedipine-PEG 1450/HPMCAS-HF solid dispersions, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is nifedipine polyethylene glycol 1450 hypromellose acetate succinateHF solid dispersion; Amorphization; DSC; FTIR; HPMCAS-HF; PEG 1450; PXRD; melt solvent method; nifedipine; solid dispersions; solubility.

Low-order high-energy nifedipine (NIF) solid dispersions (SDs) were generated by melt solvent amorphization with polyethylene glycol (PEG) 1450 and hypromellose acetate succinate (HPMCAS-HF) to increase NIF solubility while achieving acceptable phys. stability. HPMCAS-HF was used as a crystallization inhibitor. Individual formulation components, their phys. mixtures (PMs), and SDs were characterized by differential scanning calorimetry, powder X-ray diffraction, and Fourier transform IR spectroscopy (FTIR). NIF solubility and percent crystallinity (PC) were determined at the initial time and after 5 days stored at 25°C and 60% RH. FTIR indicated that hydrogen bonding was involved with the amorphization process. FTIR showed that NIF:HPMCAS-HF intermol. interactions were weaker than NIF:PEG 1450 interactions. NIF:PEG 1450 SD solubilities were significantly higher than their PM counterparts (p < 0.0001). The solubilities of NIF:PEG 1450:HPMCAS-HF SDs were significantly higher than their corresponding NIF:PEG 1450 SDs (p < 0.0001-0.043). All the SD solubilities showed a statistically significant decrease (p < 0.0001) after storage for 5 days. SDs PC were statistically lower than their comparable PMs (p < 0.0001). The PCs of SDs with HPMCAS-HF were significantly lower than SDs not containing only PEG 1450. All SDs exhibited a significant increase in PC (p < 0.0001-0.0089) on storage. Thermogravimetric anal. results showed that HPMCAS-HF bound water at higher temperatures than PEG 1450 (p < 0.0001-0.0039). HPMCAS-HF slowed the crystallization process of SDs, although it did not completely inhibit NIF crystal growth. Pharmaceutical Development and Technology published new progress about Amorphization. 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

Jin, Bo published the artcileSynthesis, Antibacterial and Anthelmintic Activity of Novel 3-(3-Pyridyl)-oxazolidinone-5-methyl Ester Derivatives, Category: pyridine-derivatives, the main research area is pyridyl oxazolidone methyl ester preparation stereoselective antibacterial anthelmintic human; anthelmintic activity; antibacterial activity; molecular docking; pyridinyl-oxazolidinone derivatives; synthesis.

In this study, a series of 3-(3-pyridyl)-oxazolidone-5-Me ester derivatives I [X = O, C(O)CH2Bn, C(O)NCy, etc.; R1 = C(O)Me, C(O)Cy, S(O)2Me, etc.] was synthesized and characterized by 1H NMR, 13C NMR and LC-MS. The conducted screening antibacterial studies of the new 3-(3-pyridyl)-oxazolidone-5-Me ester derivatives I established that the Me sulfonic acid esters have broad activity spectrum toward Staphylococcus aureus, Streptococcus pneumoniae, Bacillus subtilis and Staphylococcus epidermidis. Among them, compound I [X = O; R1 = C(O)NCy] was the most potent activity, with an MIC of 16μg/mL against B.subtilis and could reduce the instantaneous growth rate of bacteria. Furthermore, mol. docking studies were also simulated for compound I [X = O; R1 = C(O)NCy] to predict the specific binding mode of this compound In addition, anthelmintic activity of these compounds was also evaluated against adult Indian earthworms (Pheretima posthuman). The results showed that compound I [X = O, R1 = C(O)Cy] had the best effect. These results above could provided exptl. reference for the development of novel antibacterial and anthelmintic drugs.

Molecules published new progress about Anthelmintics. 26820-62-2 belongs to class pyridine-derivatives, name is 4-(5-Nitropyridin-2-yl)morpholine, and the molecular formula is C9H11N3O3, Category: pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Mahdhaoui, Faouzi published the artcileSNAr reactions of substituted pyridines with secondary amines in aqueous solution: Kinetic and reactivity indices in density functional theory, Product Details of C9H11N3O3, the main research area is nitropyridine cyclic amine nucleophilic aromatic substitution kinetics mechanism.

A kinetic study is reported for the reactions of 2-methoxy-3-nitropyridine 1a and 2-methoxy-5-nitropyridine 1b with three secondary amines 2a-c (morpholine, piperidine, and pyrrolidine) in aqueous solution at 20°C. The Bronsted-type plots are linear with βnuc = 0.52 and 0.55 for pyridines 1a and 1b, resp., indicating that the reaction proceeds through a SNAr mechanism in which the first step is the rate-determining step. Addnl. theor. calculations using the DFT/B3LYP method confirm that the C-2 carbon being the most electrophilic center for the both pyridines 1a and 1b. The second-order rate constants have been used to evaluate the electrophilicity parameters E of 1a and 1b according to the linear free energy relationship log k (20°C) = sN (N + E). The E parameters thus derived are compared with the electrophilic reactivities of a large variety of anisoles. The validity of these E values has been satisfactorily verified by comparison of calculated and exptl. second-order rate constants for the reactions of pyridines 1a and 1b with anion of Et benzylacetate.

International Journal of Chemical Kinetics published new progress about Atomic charge. 26820-62-2 belongs to class pyridine-derivatives, name is 4-(5-Nitropyridin-2-yl)morpholine, and the molecular formula is C9H11N3O3, Product Details of C9H11N3O3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Zhang, Joe Z. published the artcileEffects of Cryopreservation on Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes for Assessing Drug Safety Response Profiles, COA of Formula: C17H18N2O6, the main research area is cryopreservation human induced pluripotent stem cell cardiomyocyte; cardiac arrhythmia; cryopreservation; drug response; drug safety assessment; hiPSC-CMs; microelectrode arrays; recovery.

Burgeoning applications of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in disease modeling, regenerative medicine, and drug screening have broadened the usage of hiPSC-CMs and entailed their long-term storage. Cryopreservation is the most common approach to store hiPSC-CMs. However, the effects of cryopreservation and recovery on hiPSC-CMs remain poorly understood. Here, we characterized the transcriptome, electro-mech. function, and drug response of fresh hiPSC-CMs without cryopreservation and recovered hiPSC-CMs from cryopreservation. We found that recovered hiPSC-CMs showed upregulation of cell cycle genes, similar or reduced contractility, Ca2+ transients, and field potential duration. When subjected to treatment of drugs that affect electrophysiol. properties, recovered hiPSC-CMs showed an altered drug response and enhanced propensity for drug-induced cardiac arrhythmic events. In conclusion, fresh and recovered hiPSC-CMs do not always show comparable mol. and physiol. properties. When cryopreserved hiPSC-CMs are used for assessing drug-induced cardiac liabilities, the altered drug sensitivity needs to be considered.

Stem Cell Reports published new progress about Cardiomyocyte. 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

Abramochkin, Denis V. published the artcileA characterization of the electrophysiological properties of the cardiomyocytes from ventricle, atrium and sinus venosus of the snake heart, Related Products of pyridine-derivatives, the main research area is acetylcholine atrium ventricle sinus venosus cardiomyocyte Python; Acetylcholine; Action potential; Heart; Ionic current; Pacemaker; Python molurus; Reptile; Sinus venosus.

A detailed description of the electrophysiol. features of cardiomyocytes in the various contractile chambers of the vertebrate heart is essential to understand the evolution of cardiac elec. activity, yet very little is known about reptiles. The present study characterizes major ionic currents (INa, ICaL, IKr, IK1 and IKACh) and action potential (AP) configuration in cardiomyocytes from the ventricle, the right atrium and the sinus venosus (SV) of Burmese pythons (Python molurus) using sharp microelectrode and patch clamp recordings. Special attention was given to SV, since it consists of myocardial cells and appears to contribute to right atrial filling in snakes. We demonstrate that most of the SV in pythons has a stable resting potential of – 82.3 ± 2.6 mV (n = 9) and lacks pacemaker activity. AP duration at 50% repolarization was similar in cells from SV and atria (350.2 ± 8.7 and 330.4 ± 17.2 ms, resp.; n = 7), but shorter than ventricular APs (557.6 ± 19.2 ms, n = 5) at 30°C. The densities of ionic currents, however, differed substantially between atrial and SV cells, where the latter had much lower densities of INa, ICaL and IKr than atrial and ventricular myocytes. IK1 in ventricle was ninefold greater than in atrial cells and 23-fold greater than in myocytes from SV. However, IKACh was absent in ventricular cells, while it was equally large in atrial and SV myocytes. Consistent with this observation, APs of atrium and SV, but not ventricle, were greatly shortened upon addition of acetylcholine (10-6 M). Thus, snake SV, right atrium and ventricle have distinct patterns of ionic currents, but the resulting elec. activity is similar in atrium and SV.

Journal of Comparative Physiology, B: Biochemical, Systems, and Environmental Physiology published new progress about Cardiomyocyte. 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

Ghosh, Arunava published the artcileCellular effects of nicotine salt-containing e-liquids, Related Products of pyridine-derivatives, the main research area is calcium electronic nicotine delivery system macrophage; Ca2+; JUUL; cell; flavor; macrophage; nicotine salt.

“”Pod-based”” e-cigarettes such as JUUL are currently the most prevalent electronic nicotine delivery systems (ENDS) in the United States. JUUL-type ENDS utilize nicotine salts protonated with benzoic acid rather than freebase nicotine. However, limited information is available on the cellular effects of these products. Cytoplasmic Ca2+ is a universal second messenger that controls many cellular functions including cell growth and cell death. Of note, dysregulation of cell Ca2+ homeostasis has been linked with several disease processes including autoimmune disease and several types of cancer. We exposed HEK293T cells and THP-1 macrophage-like cells to different JUUL e-liquids We evaluated their effects on cellular viability and Ca2+ signaling by measuring fluorescence from calcein-AM/propidium iodide and Fluo-4, resp. E-liquid autofluorescence was used to look for e-liquid permeation into cells. To identify the mechanisms behind the Ca2+ responses, different inhibitors of Ca2+ channels and phospholipase C signaling were used. JUUL e-liquids caused significant cytotoxic effects, with””Mint”” flavor being the most cytotoxic. The Mint flavored e-liquid also caused a significant elevation in cytoplasmic Ca2+. Using autofluorescence, the permeation of JUUL e-liquids into live cells was confirmed, indicating that intracellular organelles are directly exposed to e-liquids Further studies identified the endoplasmic reticulum as being the source of e-liquid-induced changes in cytoplasmic Ca2+. Nicotine salt-based e-liquids cause cytotoxicity and elevate cytoplasmic Ca2+, indicating that they can exert biol. effects beyond what would be expected with nicotine alone. These effects are flavor-dependent, and we propose that flavored e-liquids be reassessed for potential lung toxicity.

Journal of Applied Toxicology published new progress about Cell adhesion. 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, Related Products of pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem