Month: December 2022

Locatelli, Marcello published the artcileFabric-Phase Sorptive Membrane Array As a Noninvasive In Vivo Sampling Device For Human Exposure To Different Compounds, Category: pyridine-derivatives, the main research area is fabric sorption membrane array human exposure sampling device.

This study introduces an innovative device for the noninvasive sampling and chromatog. anal. of different compounds present in exhaled breath aerosol (EBA). The new sampling device, especially in light of the recent COVID-19 pandemic that forced many countries to impose mandatory facemasks, allows an easy monitoring of the subject′s exposure to different compounds they may come in contact with, actively or passively. The project combines the advantages of a fabric-phase sorptive membrane (FPSM) as an in vivo sampling device with a validated LC-MS/MS screening procedure able to monitor more than 739 chems. with an overall anal. time of 18 min. The project involves the noninvasive in vivo sampling of the EBA using an FPSM array inserted inside an FFP2 mask. The study involved 15 healthy volunteers, and no restrictions were imposed during or prior to the sampling process regarding the consumption of drinks, food, or drugs. The FPSM array-LC-MS/MS approach allowed us to effectively exploit the advantages of the two complementary procedures (the convenient sampling by an FPSM array and the rapid anal. by LC-MS/MS), obtaining a powerful and green tool to carry out rapid screening analyses for human exposure to different compounds The flexible fabric substrate, the sponge-like porous architecture of the high-efficiency sol-gel sorbent coating, the availability of a large cache of sorbent coatings, including polar, nonpolar, mixed mode, and zwitterionic phases, the easy installation into the facemask, and the possibility of sampling without interrupting regular activities provide FPSMs unparalleled advantages over other sampling techniques, and their applications are expected to expand to many other clin. or toxicol. studies.

Analytical Chemistry (Washington, DC, United States) published new progress about Drugs. 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

Jamei, Masoud published the artcileCurrent status and future opportunities for incorporation of dissolution data in PBPK modeling for pharmaceutical development and regulatory applications: OrBiTo consortium commentary, Application of 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is pharmaceutical pharmacokinetics felodipine ibuprofen; Biorelevant dissolution; Dissolution; Oral drug absorption; PBBM (Physiologically Based Biopharmaceutical Model); PBPK.

In vitro dissolution experiments are used to qual. assess the impact of formulation composition and process changes on the drug dosage form performance. However, the use of dissolution data to quant. predict changes in the absorption profile remains limited. Physiol.-based Pharmacokinetic(s) (PBPK) models facilitate incorporation of in vitro dissolution experiments into mechanistic oral absorption models to predict in vivo oral formulation performance, and verify if the drug product dissolution method is biopredictive or clin. relevant. Nevertheless, a standardized approach for using dissolution data within PBPK models does not yet exist and the introduction of dissolution data in PBPK relies on a case by case approach which accommodates from differences in release mechanism and limitations to drug absorption. As part of the Innovative Medicines Initiative (IMI) Oral Biopharmaceutics Tools (OrBiTo) project a cross-work package was set up to gather a realistic understanding of various approaches used and their areas of applications. This paper presents the approaches shared by academic and industrial scientists through the OrBiTo project to integrate dissolution data within PBPK software to improve the prediction accuracy of oral formulations in vivo. Some general recommendations regarding current use and future improvements are also provided.

European Journal of Pharmaceutics and Biopharmaceutics published new progress about Cecum. 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 of 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Asakawa, Chiharu published the artcile[11C]Sorafenib: Radiosynthesis and preliminary PET study of brain uptake in P-gp/Bcrp knockout mice, Application of Methyl 4-chloropicolinate, the main research area is carbon 11 sorafenib preparation PET imaging brain.

Sorafenib (Nexavar, BAY43-9006, 1) is a second-generation, orally active multikinase inhibitor that is approved for the treatment of some cancers in patients. In this Letter, we developed [11C]1 as a novel positron emission tomog. (PET) probe, and evaluated the influence of ABC transporters-mediated efflux on brain uptake using PET with [11C]1 in P-glycoprotein (P-gp)/breast cancer resistance protein (Bcrp) knockout mice vs. wild-type mice. [11C]1 was synthesized by the reaction of hydrochloride of aniline 2 with [11C]phosgene ([11C]COCl2) to give isocyanate [11C]6, followed by reaction with another aniline 3. Small-animal PET study with [11C]1 indicated that the radioactivity level (AUC0-60 min, SUV × min) in the brains of P-gp/Bcrp knockout mice was about three times higher than in wild-type mice.

Bioorganic & Medicinal Chemistry Letters published new progress about Brain. 24484-93-3 belongs to class pyridine-derivatives, name is Methyl 4-chloropicolinate, and the molecular formula is C7H6ClNO2, Application of Methyl 4-chloropicolinate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Wadsworth, Harry published the artcileExploration of the structure-activity relationship of the diaryl anilide class of ligands for translocator protein-potential novel positron emitting tomography imaging agents, Formula: C7H7NO2, the main research area is PET imaging diaryl anilide preparation translocator protein ligand SAR.

A series of novel ligands based on the diaryl anilide (DAA) class of translocator protein (TSPO) ligands was synthesized and evaluated as potential positron emitting tomog. (PET) ligands for imaging TPSO in vivo. Fluorine-18 labeling of the mols. was achieved using direct radiolabelling or synthon based labeling approaches. Several of the ligands prepared have promising profiles as potential TSPO PET imaging ligands and will be evaluated further as potential clin. imaging agents.

Bioorganic & Medicinal Chemistry Letters published new progress about Brain. 71255-09-9 belongs to class pyridine-derivatives, name is 2-Methoxynicotinaldehyde, and the molecular formula is C7H7NO2, Formula: C7H7NO2.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Chatzistavraki, Maria published the artcileAmyloid β-protein precursor regulates depolarization-induced calcium-mediated synaptic signaling in brain slices, SDS of cas: 21829-25-4, the main research area is amyloid protein depolarization calcium signaling brain slice; Alzheimer’s disease; AβPP; amyloid-β protein precursor; calcium; neuronal signaling; synapse.

Coordinated calcium influx upon neuronal depolarization activates pathways that phosphorylate CaMKII, ERKs, and the transcription factor CREB and, therefore, expression of pro-survival and neuroprotective genes. Recent evidence indicates that amyloid-β protein precursor (AβPP) is trafficked to synapses and promotes their formation. At the synapse, AβPP interacts with synaptic proteins involved in vesicle exocytosis and affects calcium channel function. Herein, we examined the role of AβPP in depolarization-induced calcium-mediated signaling using acute cerebral slices from wild-type C57bl/6 mice and AβPP-/- C57bl/6 mice. Depolarization of acute cerebral slices from wild-type C57bl/6 and AβPP-/- C57bl/6 mice was used to induce synaptic signaling. Protein levels were examined by western blot and calcium dynamics were assessed using primary neuronal cultures. In the absence of AβPP, decreased pCaMKII and pERKs levels were observed This decrease was sensitive to the inhibition of N- and P/Q-type Voltage Gated Calcium Channels (N- and P/Q-VGCCs) by ω-conotoxin GVIA and ω-conotoxin MVIIC, resp., but not to inhibition of L-type VGCCs by nifedipine. However, the absence of AβPP did not result in a statistically significant decrease of pCREB, which is a known substrate of pERKs. Finally, using calcium imaging, we found that down regulation of AβPP in cortical neurons results in a decreased response to depolarization and altered kinetics of calcium response. AβPP regulates synaptic activity-mediated neuronal signaling by affecting N- and P/Q-VGCCs.

Journal of Alzheimer’s Disease published new progress about Brain. 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

Rousset, Matthieu published the artcileMammalian Brain Ca2+ Channel Activity Transplanted into Xenopus laevis Oocytes, Quality Control of 21829-25-4, the main research area is calcium channel Xenopus laevis oocyte mammalian brain; CaV2 Ca2+ channels; channelopathies; membrane microtransplantation; voltage clamp.

Several mutations on neuronal voltage-gated Ca2+ channels (VGCC) have been shown to cause neurol. disorders and contribute to the initiation of epileptic seizures, migraines, or cerebellar degeneration. Anal. of the functional consequences of these mutations mainly uses heterologously expressed mutated channels or transgenic mice which mimic these pathologies, since direct electrophysiol. approaches on brain samples are not easily feasible. We demonstrate that mammalian voltage-gated Ca2+ channels from membrane preparation can be microtransplanted into Xenopus oocytes and can conserve their activity. This method, originally described to study the alteration of GABA receptors in human brain samples, allows the recording of the activity of membrane receptors and channels with their native post-translational processing, membrane environment, and regulatory subunits. The use of hippocampal, cerebellar, or cardiac membrane preparation displayed different efficacy for transplanted Ca2+ channel activity. This technique, now extended to the recording of Ca2+ channel activity, may therefore be useful in order to analyze the calcium signature of membrane preparations from unfixed human brain samples or normal and transgenic mice.

Membranes (Basel, Switzerland) published new progress about Brain. 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, Quality Control of 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Cornelissen, Lisa G. H. published the artcileThe diagnostic value of fetal fibronectin testing in clinical practice, Product Details of C17H18N2O6, the main research area is fetal fibronectin testing diagnostic value; cervical length; cervical length measurement; fetal fibronectin; preterm delivery.

To evaluate the clin. management to withhold treatment for preterm labor in symptomatic women with an intermediate cervical length and neg. fetal fibronectin (fFN) testing. A retrospective cohort study was performed in a tertiary care teaching hospital in the Netherlands. Pregnant women with a gestational age between 23+5 to 34+0 weeks, with the presence of regular uterine contractions accompanied by a cervical length between 15 and 30 mm and intact membranes, who underwent fFN testing were included to obtain the diagnostic value of fFN testing for preterm delivery within 7 days. Fetal fibronectin testing has an extremely high neg. predictive value (100%) and sensitivity (100%) for delivery within 7 days, in singleton and multiple pregnancies. However, specificity (64%) and pos. predictive value (10%) of fFN testing in singleton pregnancies are low. Blood present on the fFN sample does not affect the reliability of the fFN test; the neg. predictive value remains 100%. Women with symptoms of early preterm labor, intact membranes, a cervical length between 15 and 30 mm and neg. fFN testing do not deliver within 7 days. Administration of corticosteroids and tocolytics can safely be withhold. Furthermore, blood on the fFN sample does not change the reliability of the fFN test.

Journal of Obstetrics and Gynaecology Research published new progress about Blood. 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, Product Details of C17H18N2O6.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Kim, Hyung Min published the artcileSimultaneous determination of cardiovascular drugs in dried blood spot by liquid chromatography-tandem mass spectrometry, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is blood cardiovascular drug amlodipine atenolol atorvastatin digoxin LC MS; Cardiovascular drugs; Dried blood spot; LC-MS/MS; Therapeutic drug monitoring.

A dried blood spot (DBS) sampling method was exploited to extract cardiovascular drugs using a small volume of whole blood of human and rodent. Thereafter, an anal. method using liquid chromatog. with tandem mass spectrometry (LC-MS/MS) was developed and validated for the determination of 12 cardiovascular drugs. A 6 mm internal diameter disk containing 10μL of blood was punched from a specifically designed card and analyzed by LC-MS/MS using a gradient elution method with a total run time of 16 min. For sample separation, a universal octadecyl-silica column was used with a flow rate of 0.2 mL/min. The developed method was validated in terms of linearity, accuracy, and precision, which showed satisfactory results. In addition, the matrix effects were closely investigated to confirm the extraction efficiency. Addnl., the stability was tested by storing DBSs at room temperature; the results showed that these drugs were stable for at least 30 days. Accordingly, the proposed LC-MS/MS method is capable to analyze several cardiovascular drugs in a single anal. It can be applied to therapeutic drug monitoring in patients as well as in the in vivo settings.

Journal of Food and Drug Analysis published new progress about Blood. 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

Adeyemi, Oladipupo published the artcileA pharmacological characterization of electrocardiogram PR and QRS intervals in conscious telemetered rats, Application In Synthesis of 21829-25-4, the main research area is ECG pharmacol agent radiotelemetry; Diltiazem; Electrocardiogram; Flecainide; Methods; Nifedipine; Quinidine; Rat; Telemetry; Translation; Verapamil.

The current study aimed to identify its utility in assessing ECG (ECG) PR and QRS interval changes. Male Han-Wistar rats (~250 g) were implanted with radio-telemetry devices for the recording of ECG and haemodynamic parameters. Animals (n = 4-8) were treated with single doses of calcium (nifedipine, diltiazem or verapamil; CCBs) or sodium channel blockers (quinidine or flecainide; SCBs) or their corresponding vehicles in an ascending dose design. Pharmacokinetic anal. of blood samples was performed to allow comparison of effects to published data in other species. Of the CCBs, only diltiazem (300 mg/kg) prolonged the PR interval (49 ± 2 vs. vehicle: 43 ± 1 ms), although this was not statistically significant (p = .11). QA interval decreased with nifedipine (30 ± 1 vs. 24 ± 0 ms) and diltiazem (34 ± 1 vs. 27 ± 1 ms) but increased with verapamil (30 ± 0 vs. 37 ± 1 ms) demonstrating pharmacol. activity of each agent. Both SCBs, caused statistically significant (p < .05) increases in both intervals - quinidine (100 mg/kg; PR: 50 ± 2 vs. 43 ± 1 ms; QRS: 22 ± 2 vs. 18 ± 1 ms) and flecainide (9 mg/kg; PR: 56 ± 1 vs. 46 ± 1 ms; QRS: 27 ± 1 vs. 21 ± 1 ms). At similar plasma concentrations to other species, the conscious telemetered rat demonstrates limited utility in assessing PR interval prolongation by CCBs, despite significant contractility effects being observed However, results with SCBs demonstrate a potential application for evaluating drug-induced QRS prolongation. Journal of Pharmacological and Toxicological Methods published new progress about Blood. 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

Han, Xiuyuan published the artcileEffect Of epigallocatechin-3-gallate on the pharmacokinetics of amlodipine in rats, Product Details of C18H19Cl2NO4, the main research area is liver microsome amlodipine EGCG pharmacokinetics; Drug–drug interaction; EGCG; LC-MS/MS; amlodipine; pharmacokinetics.

This study investigates the effect of epigallocatechin-3-gallate (EGCG), a major ingredient of green tea, on the pharmacokinetics of amlodipine in rats. The pharmacokinetics of orally administered amlodipine (1 mg/kg) with or without EGCG pretreatment (30 mg/kg/day for 10 days) were investigated. Plasma concentrations of amlodipine were determined by using a sensitive and reliable liquid chromatog. with tandem mass spectroscopy (LC-MS/MS) method. The effects of EGCG on the metabolic stability of amlodipine were investigated by using rat liver microsome incubation systems. The results indicated that when the rats were pretreated with EGCG, the Cmax of amlodipine increased from 16.32 ± 2.57 to 21.44 ± 3.56 ng/mL (p < 0.05), the Tmax decreased from 5.98 ± 1.25 to 4.01 ± 1.02 h (p < 0.05), and the AUC0-t increased from 258.12 ± 76.25 to 383.34 ± 86.95 mug h L-1 (p < 0.05), which suggested that the pharmacokinetic behavior of amlodipine was affected after oral co-administration of EGCG. Addnl., the metabolic half-life was prolonged from 31.3 ± 5.6 to 52.6 ± 7.9 min (p < 0.05) with the pretreatment of EGCG. It can be speculated that the drug-drug interaction between EGCG and amlodipine might occur, which might have resulted from the metabolism inhibition of amlodipine by EGCG when they were co-administered. Xenobiotica published new progress about Blood. 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