Category: 21829-25-4

Hartung, Jane E. published the artcileVoltage-gated calcium currents in human dorsal root ganglion neurons, Quality Control of 21829-25-4, the publication is Pain (2022), 163(6), e774-e785, database is CAplus and MEDLINE.

Voltage-gated calcium channels in sensory neurons underlie processes ranging from neurotransmitter release to gene expression and remain a therapeutic target for the treatment of pain. Yet virtually all we know about voltage-gated calcium channels has been obtained through the study of rodent sensory neurons and heterologously expressed channels. To address this, high voltage-activated (HVA) Ca²⁺ currents in dissociated human and rat dorsal root ganglion neurons were characterized with whole-cell patch clamp techniques. The HVA currents from both species shared basic biophys. and pharmacol. properties. However, HVA currents in human neurons differed from those in the rat in at least 3 potentially important ways: (1) Ca²⁺ c.d. was significantly smaller, (2) the proportion of nifedipine-sensitive currents was far greater, and (3) a subpopulation of human neurons displayed relatively large constitutive current inhibition. These results highlight the need to for the study of native proteins in their native environment before initiating costly clin. trials.

Pain published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, 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:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Santana-Mateos, Marta published the artcileClinical and Pharmacological Parameters Determine Relapse During Clopidogrel Treatment of Acute Coronary Syndrome, Product Details of C17H18N2O6, the publication is Journal of Clinical Pharmacology (2022), 62(6), 783-791, database is CAplus and MEDLINE.

The therapeutic efficacy of clopidogrel as an antiplatelet drug varies among individuals, being the mainstream hypothesis that its bioavailability depends on the individual genetic background and/or interactions with other drugs. A total of 477 patients receiving double antiaggregation therapy with aspirin and clopidogrel, after suffering a first event, were followed for 1 yr to record relapse, as a surrogate end point to measure their therapeutic response, as defined by presenting with an acute coronary event (unstable angina, ST-segment-elevation myocardial infarction, or non-ST-segment-elevation myocardial infarction), stent thrombosis/restenosis, or cardiac mortality. Anthropometric, clin., and pharmacol. variables along with CYP2C19 genotypes were analyzed for their association with the disease relapse phenotype. Only 75 patients (15%) suffered a relapse, which occurred during the first 6 mo of therapy, with a peak at 4.5 mo. An initial univariate anal. identified that patients in the relapse group were significantly older (67.4 ± 11.0 vs 61.6 ± 12.3 years old) and presented with diffuse coronary disease, insulin-dependent type 2 diabetes mellitus dyslipidemia, and arterial hypertension. A poor clin. response to the platelet antiaggregation regime also occurred more frequently among patients taking acenocoumarol and calcium channel blockers, along with aspirin and clopidogrel, while no association was found according to CYP2C19 genotypes. A retrospective multivariate anal. indicated that patients belonging to the nonresponder phenotype to treatment with aspirin and clopidogrel were older, presented with diffuse coronary disease, a group largely overlapping with type 2 insulin-dependent diabetes mellitus, and were taking dihidropyrimidinic calcium channel blockers.

Journal of Clinical Pharmacology published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, 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:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Yin, Jinjin published the artcileNifedipine or amlodipine? The choice for hypertension during pregnancy: a systematic review and meta-analysis, Safety of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the publication is Archives of Gynecology and Obstetrics, database is CAplus and MEDLINE.

There is a lack of sufficient evidence regarding efficacy and safety of amlodipine on treating hypertension during pregnancy. To compare antihypertensive efficacy, pregnancy outcome and safety of amlodipine with nifedipine on hypertension during pregnancy. A systematic search of PubMed, Embase, Cochrane Library, clinicaltrials.gov, Chinese National Knowledge Infrastructure, Wanfang Database and China Biol. Medicine disk of randomized controlled trials (RCTs) up to Apr. l5, 2021 was conducted on RCTs comparing amlodipine to nifedipine for the treatment of hypertension during pregnancy. Screening, data extraction, and quality assessment were done by two independent reviewers. To estimate relative effects from all available evidence, a meta-anal. was conducted. Seventeen RCTs were included. Amlodipine was found the efficacy is slightly superior to nifedipine on treating hypertension during pregnancy (RR 1.06, 95% CI 1.01 to 1.10) with a decreased risk for maternal side effects (RR 0.42, 95% CI 0.29 to 0.61). Subgroup anal. found amlodipine can get a better control on SBP (RR – 11.68, 95% CI – 17.98 to – 5.37) and DBP (RR – 7.44, 95% CI – 13.81 to – 1.06) compared with intermediate-/long-acting nifedipine. In addition, there was no difference between amlodipine and nifedipine on pregnancy outcomes including caesarean section, premature labour, placental abruption, FGR, fetal distress, neonatal asphyxia. Given the results of this systematic review and meta-anal., amlodipine can be effectively and safely used for hypertension during pregnancy.

Archives of Gynecology and Obstetrics published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C5H10O, Safety of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Souza de Araujo, Guilherme Rodolfo published the artcileMicroemulsions formed by PPG-5-CETETH-20 at low concentrations for transdermal delivery of nifedipine: Structural and in vitro study, Application In Synthesis of 21829-25-4, the publication is Colloids and Surfaces, B: Biointerfaces (2022), 112474, database is CAplus and MEDLINE.

Nifedipine is a potent anti-hypertensive, which is poorly orally bioavailable on account of first-pass metabolism, short half-life, and low water solubility This study aimed to develop a microemulsified system with low surfactant concentration and to evaluate the influence of microemulsion (ME) phase behavior on skin permeation of nifedipine, as drug model. Thereafter, MEs were obtained using PPG-5-CETETH-20, oleic acid, and phosphate buffer at pH 5.0. The selected MEs were isotropic, with droplet diameters less than 10 nm, polydispersity index < 0.25, and pH between 5.0 and 5.2. MEs presented low viscosity and Newtonian behavior. SAXS results confirmed bicontinuous and oil-in-water (o/w) MEs formation. The presence of the drug promoted only very slight modifications in the ME structure. The MEs presented ability to deliver nifedipine via the transdermal route when in comparison with the control. Nevertheless, the skin permeated and retained amounts from the o/w and bicontinuous formulations did not differ significantly. The ATR-FTIR demonstrated that both formulations promoted fluidization and disorganization of lipids and increased the drug diffusion and partition coefficients in the skin. In conclusion, PPG-5-CETETH-20 MEs obtained proved to be effective skin permeation enhancers, acting by rising the coefficients of partition and diffusion of the nifedipine in the skin.

Colloids and Surfaces, B: Biointerfaces published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C15H14N2, Application In Synthesis of 21829-25-4.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Michiba, Kazuyoshi published the artcileUsefulness of human jejunal spheroid-derived differentiated intestinal epithelial cells for the prediction of intestinal drug absorption in humans, Product Details of C17H18N2O6, the publication is Drug Metabolism & Disposition (2022), 50(3), 204-213, database is CAplus and MEDLINE.

This study aimed to demonstrate the usefulness of human jejunal spheroid-derived differentiated intestinal epithelial cells as a novel in vitro model for clarifying the impact of intestinal drug-metabolizing enzymes and transporters on the intestinal absorption of substrate drugs in humans. Three-dimensional human intestinal spheroids were successfully established from surgical human jejunal specimens and expanded for a long period using L-WRN-conditioned medium, which contains Wnt3a, R-spondin 3, and noggin. The mRNA expression levels of intestinal pharmacokinetics-related genes in the human jejunal spheroid-derived differentiated intestinal epithelial cells were drastically increased over a 5-day period after seeding compared with those in human jejunal spheroids and were approx. the same as those in human jejunal tissue over a culture period of at least 13 days. Activities of typical drug-metabolizing enzymes [cytochrome P 450 (CYP) 3A, CYP2C9, uridine 5-diphospho-glucuronosyltransferase 1A, and carboxylesterase 2] and uptake/efflux transporters [peptide transporter 1/solute carrier 15A1], P-glycoprotein, and breast cancer resistance protein) in the differentiated cells were confirmed. Furthermore, intestinal availability (Fg) values estimated from the apical-to-basolateral permeation clearance across cell monolayer showed a good correlation with the in vivo Fg values in humans for five CYP3A substrate drugs (Fg range, 0.35-0.98). In conclusion, the functions of major intestinal drug-metabolizing enzymes and transporters could be maintained in human jejunal spheroid-derived differentiated intestinal epithelial cells. This model would be useful for the quant. evaluation of the impact of intestinal drug-metabolizing enzymes and transporters on the intestinal absorption of substrate drugs in humans.

Drug Metabolism & Disposition published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, 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:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Zhang, Xudong published the artcileHergSPred: Accurate Classification of hERG Blockers/Nonblockers with Machine-Learning Models, Safety of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the publication is Journal of Chemical Information and Modeling (2022), 62(8), 1830-1839, database is CAplus and MEDLINE.

The human ether-á-go-go-related gene (hERG) K+ channel plays an important role in cardiac action potentials. The inhibition of the hERG channel may lead to long QT syndrome (LQTS) and even sudden cardiac death. Due to severe hERG-related cardiotoxicity, many drugs have been withdrawn from the market. Therefore, it is necessary to estimate the chem. blockade of hERG in the early stage of drug discovery. In this study, we collected 12,850 compounds with hERG inhibition data from the literature and trained a series of hERG blocking classification models based on the MACCS and Morgan fingerprints. A consensus model named HergSPred was generated based on the individual models using voting principles. The accuracy of HergSPred is higher than previous models using identical training and test sets. Moreover, we analyzed the contribution of each input fingerprint to the prediction output to obtain intuitive chem. insights into the hERG inhibition, which allows visualization of warning substructures that may cause cardiotoxicity in the input compound The model is available at http://www.icdrug.com/ICDrug/T.

Journal of Chemical Information and Modeling published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H37NO3, Safety of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Lauro, Figueroa-Valverde published the artcileSynthesis and Biological Activity of the Pyridine-hexacyclic-steroid Derivative on a Heart Failure Model., Computed Properties of 21829-25-4, the publication is Anti-inflammatory & anti-allergy agents in medicinal chemistry (2022), 21(1), 34-45, database is MEDLINE.

BACKGROUND: Several drugs with inotropic activity have been synthesized; however, there is very little information on biological activity exerted by steroid derivatives in the cardiovascular system. OBJECTIVE: The aim of this research was to prepare a steroid-pyridine derivative to evaluate the effect it exerts on left ventricular pressure and characterize its molecular interaction. METHODS: The first stage was carried out through the synthesis of a steroid-pyridine derivative using some chemical strategies. The second stage involved the evaluation of the biological activity of the steroid-pyridine derivative on left ventricular pressure using a model of heart failure in the absence or presence of the drugs, such as flutamide, tamoxifen, prazosin, metoprolol, indomethacin, and nifedipine. RESULTS: The results showed that steroid-pyridine derivative increased left ventricular pressure in a dose-dependent manner (0.001-100 nM); however, this phenomenon was significantly inhibited only by nifedipine at a dose of 1 nM. These results indicate that positive inotropic activity produced by the steroid-pyridine derivative was via calcium channel activation. Furthermore, the biological activity exerted by the steroid-pyridine derivative on the left ventricle produces changes in cAMP concentration. CONCLUSION: It is noteworthy that positive inotropic activity produced by this steroid-pyridine derivative involves a different molecular mechanism compared to other positive inotropic drugs. Therefore, this steroid could be a good candidate for the treatment of heart failure.

Anti-inflammatory & anti-allergy agents in medicinal chemistry published new progress about 21829-25-4. 21829-25-4 belongs to pyridine-derivatives, auxiliary class Membrane Transporter/Ion Channel,Calcium Channel, 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:
https://en.wikipedia.org/wiki/Pyridine,
Pyridine | C5H5N – PubChem

Cobine, Caroline A. published the artcileRhythmic calcium transients in smooth muscle cells of the mouse internal anal sphincter, Application In Synthesis of 21829-25-4, the main research area is calcium transient smooth muscle cell internal analysis sphincter; gastrointestinal; interstitial cells of Cajal; pacemaker; slow wave; tone.

Ca2+ transients displayed ongoing rhythmic firings at both lengths and were abolished by nifedipine and the KATP channel activator pinacidil indicating their dependence upon CavL. Like SWs, CTs were greatest in frequency and amplitude at the distal extremity and conducted proximally. Removal of the distal IAS reduced but did not abolish CTs. The time constant for clearing cytoplasmic Ca2+ averaged 0.46 s and basal Ca2+ levels were significantly elevated. The similarities in spatiotemporal and pharmacol. properties of CTs and SWs suggest that SW gives rise to CTs while muscle stretch is not required. Elevated relative basal Ca2+ in the IAS is likely due to the inability of cells to clear or sequester Ca2+ between rapid frequency voltage-dependent Ca2+ entry events, i.e., conditions that will lead to tone development. The conduction of CTs from distal to proximal IAS will lead to orally directed contractions and likely contribute to the maintenance of fecal continence.

Neurogastroenterology & Motility published new progress about Cytoplasm. 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

Shen, Hsuan-Shu published the artcileChinese herbal medicines have potentially beneficial effects on the perinatal outcomes of pregnant women, HPLC of Formula: 21829-25-4, the main research area is chinese herbal medicine premature birth miscarriage population; Chinese herbal products; National health insurance research database; preterm labor; threatened miscarriage; tocolytic treatment.

Tocolytic treatment is beneficial to pregnant women with a risk of premature labor or miscarriage. However, previous reports have shown that progestogen might not be effective and ritodrine may increase the risk of maternal vascular-related diseases. Chinese herbal products (CHP) are used as alternative therapies for pregnant women. The goal was to evaluate the efficacy of combined tocolytic therapy and CHP therapy in pregnancy outcomes for pregnant women in Taiwan. We conducted a retrospective cohort study based on the National Health Insurance Research Database. A total of 47,153 pregnantwomen treatedwith tocolytics aged 18-50 years from 2001 to 2015 were selected from two million random samples. According to the medical use of tocolytics and CHP, we divided the users into two groups: westernmedicine (WM) only (n = 40,961) andWM/CHP (n = 6,192) groups. A propensity score (PS)-matched cohort (6,192 pairs) was established based on baseline confounders. All participants were followed up to perinatal outcomes. Conditional logistic regression anal. was used to examine the effects of CHP use on the odds of miscarriage and preterm birth. The adjusted odds ratio (OR) for premature birth in the WM/CHP group (n = 411, 6.64%) was significantly lower than in the WM group (n = 471, 7,61%) (0,86, 95% confidence interval [CI], 0.74-0.99). Further subgroup anal. based on the usage of formulas that activate blood and remove stasis or purgative formulas, the adjusted OR of preterm birth of those using these formulas was significantly lower in theWM/CHP group (n = 215, 6.32%) than that in theWM group (n = 265, 7.77%) (OR: 0.79, 95% CI: 0.65-0.96). We found that the combination of CHP and tocolytics can be beneficial to pregnant women in the prevention of premature birth. Further research is required to investigate causal relationships.

Frontiers in Pharmacology published new progress about Abortion. 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, HPLC of Formula: 21829-25-4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Hong, Ji Young published the artcileAntenatal magnesium sulfate treatment and risk of necrotizing enterocolitis in preterm infants born at less than 32 weeks of gestation, Product Details of C17H18N2O6, the main research area is necrotizing enterocolitis gestation magnesium sulfate.

Abstract: Antenatal magnesium sulfate (MgSO4) treatment is widely used for fetal neuroprotection in women at risk of preterm delivery. However, some studies have recently suggested that in utero MgSO4 exposure is associated with an increased risk of necrotizing enterocolitis (NEC). This study aimed to investigate the association between antenatal MgSO4 treatment and risk of NEC. This retrospective cohort study included 756 infants born at 24-31 wk gestation. Subjects were classified into three groups: period 1, when MgSO4 treatment protocol for fetal neuroprotection was not adopted (n = 267); period 2, when the protocol was adopted (n = 261); and period 3, when the protocol was withdrawn because of concern of risk of NEC (n = 228). Rates of NEC (�stage 2b) were analyzed according to time period and exposure to antenatal MgSO4. Significant difference in the rate of NEC was not found across the three time periods (2.6% vs. 6.5% vs. 4.8% in periods 1, 2 and 3, resp., p = 0.103). The rate of NEC was comparable between the infants exposed and unexposed to antenatal MgSO4 (5.1% vs. 3.6%, p = 0.369). These results showed that antenatal MgSO4 treatment was not associated with risk of NEC in our study population.

Scientific Reports published new progress about Acidosis. 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