Day: November 30, 2022

Catic-Djordjevic, Aleksandra published the artcileAssessment of pharmacokinetic mycophenolic acid clearance models using Monte Carlo numerical analysis, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is mycophenolic acid pharmacokinetics Monte Carlo simulation; Monte Carlo simulation; Mycophenolic acid; clearance; population pharmacokinetic analysis; renal transplant patients.

Previously, we performed population pharmacokinetic anal. and indicated age, mycophenolate mofetil (MMF)/mycophenolic acid (MPA) daily dose, and presence of nifedipine in patient therapy as significant predictors of MPA apparent clearance (CL/F) variability. This study aimed to determine the reliability of previously published population pharmacokinetic models derived from similar studies. Furthermore, this study investigated correspondence between chosen population models from the literature. By means of the Monte Carlo simulation method, pharmacokinetic models from different studies are simulated and analyzed in the range of standard deviations of measured system parameters as well as the range of observed model parameters taken from the comparison studies. The 1000 numerical simulations were performed for every analyzed model in order to calculate the most possible MPA CL/F values according to the expected values from the performed experiment Fitting our results with other models showed how the presence of nifedipine makes difference in MPA CL/F values. By testing the data from selected studies into our model, a similar range of expected CL/F values was obtained, which may confirm the validity of our model. The results of our population pharmacokinetic study are partially applicable in models by other researchers.

Xenobiotica published new progress about Albumins Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

Wang, Xinxin published the artcileDiltiazem inhibits SARS-CoV-2 cell attachment and internalization and decreases the viral infection in mouse lung, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is diltiazem antiviral agent cell attachment internalization SARS CoV2 infection.

The continuous emergence of severe acute respiratory coronavirus 2 (SARS-CoV-2) variants and the increasing number of breakthrough infection cases among vaccinated people support the urgent need for research and development of antiviral drugs. Viral entry is an intriguing target for antiviral drug development. We found that diltiazem, a blocker of the L-type calcium channel Cav1.2 pore-forming subunit (Cav1.2 α1c) and an FDA-approved drug, inhibits the binding and internalization of SARS-CoV-2, and decreases SARS-CoV-2 infection in cells and mouse lung. Cav1.2 α1c interacts with SARS-CoV-2 spike protein and ACE2, and affects the attachment and internalization of SARS-CoV-2. Our finding suggests that diltiazem has potential as a drug against SARS-CoV-2 infection and that Cav1.2 α1c is a promising target for antiviral drug development for COVID-19.

PLoS Pathogens published new progress about 28S rRNA Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

Zhang, Shutao published the artcileFelodipine enhances aminoglycosides efficacy against implant infections caused by methicillin-resistant Staphylococcus aureus, persisters and biofilms, Synthetic Route of 72509-76-3, the main research area is felodipine aminoglycoside methicillin resistant Staphylococcus aureus biofilm; Aminoglycosides; Felodipine; Implant infection; Methicillin-resistant Staphylococcus aureus; Persisters.

Methicillin-resistant Staphylococcus aureus (MRSA), biofilms, and persisters are three major factors leading to recurrent and recalcitrant implant infections. Although antibiotics are still the primary treatment for chronic implant infections in clin., only few drugs are effective in clearing persisters and formed biofilms. Here, felodipine, a dihydropyridine calcium channel blocker, was reported for the first time to have antibacterial effects against MRSA, biofilm, and persisters. Even after continuous exposure to sub-lethal concentrations of felodipine, bacteria are less likely to develop resistance. Besides, low doses of felodipine enhances the antibacterial activity of gentamicin by inhibiting the expression of protein associated with aminoglycoside resistance (aacA-aphD). Next, biofilm eradication test and persisters killing assay suggested felodipine has an excellent bactericidal effect against formed biofilms and persisters. Furthermore, the result of protein profiling, and quant. metabonomics anal. indicated felodipine reduce MRSA virulence (agrABC), biofilm formation and TCA cycle. Then, mol. docking showed felodipine inhibit the growth of persisters by binding to the H pocket of ClpP protease, which could lead to substantial protein degradation Furthermore, murine infection models suggested felodipine in combination with gentamicin alleviate bacterial burden and inflammatory response. In conclusion, low dose of felodipine might be a promising agent for biomaterial delivery to enhance aminoglycosides efficacy against implant infections caused by MRSA, biofilm, and persisters.

Bioactive Materials published new progress about 16S rRNA Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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, Synthetic Route of 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Zimmermann, Viktor published the artcileChemoselective reduction of nitroarenes in the presence of acid-sensitive functional groups: Solid-phase syntheses of amino aryl azides and benzotriazoles, Application In Synthesis of 36437-30-6, the main research area is chemoselective reduction nitroarene acid sensitive functional group present; solid phase synthesis amino aryl azide benzotriazole.

The authors demonstrated the 1st chemoselective reduction of nitroarenes on solid supports in the presence of other reducible functional groups such as triazenes. A unique combination of a single-electron transfer reagent (viologen) with Na2S proved to be convenient in terms of reducing the strength and for the workup. The relatively long reaction times appear justified, considering the possibilities for further diversification of yielded aminoarenes on solid supports. From o-nitroanilines, for example, >95% 5-methyl-1H-benzotriazole was obtained from 5-methyl-2-nitroaniline via formation of the diazonium tetrafluoroborate, reaction with [(benzylamino)methyl]-modified polystyrene (from Merrifield resin) to give a supported triazene, selective reduction using Na2S/K2CO3/1,1′-dioctyl-4,4′-bipyridinium(2+) dibromide, and cleavage of the resin using 5% trifluoroacetic acid in the presence of TMSN3. Azidoanilines were formed by the above sequence from 4-nitroaniline and Me 5-amino-2-nitrobenzoate.

Journal of Combinatorial Chemistry published new progress about Aromatic amines Role: SPN (Synthetic Preparation), PREP (Preparation) (azido). 36437-30-6 belongs to class pyridine-derivatives, name is 1,1-Di-n-octyl-4,4-bipyridinium Dibromide, and the molecular formula is C26H42Br2N2, Application In Synthesis of 36437-30-6.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Nakayama, Yohei published the artcileFollicular dendritic cell-secreted protein gene expression is upregulated and spread in nifedipine-induced gingival overgrowth, HPLC of Formula: 21829-25-4, the main research area is gingival dendritic cell gene expression; AMTN; FDC-SP; Gingival overgrowth; Junctional epithelium; Nifedipine.

Abstract: Follicular dendritic cell-secreted protein (FDC-SP) is secreted protein expressed in follicular dendritic cells, periodontal ligament and junctional epithelium (JE). Its expression could be controlled during inflammatory process of gingiva; however, responsible mechanism for gingival overgrowth and involvement of FDC-SP in clin. condition is still unclear. We hypothesized that JE-specific genes are associated with the initiation of drug-induced gingival enlargement called gingival overgrowth, and investigated the changes of JE-specific genes expression and their localization in overgrown gingiva from the patients. Immunohistochem. anal. revealed that the FDC-SP localization was spread in overgrown gingival tissues. FDC-SP mRNA levels in GE1 and Ca9-22 cells were increased by time-dependent nifedipine treatments, similar to other JE-specific genes, such as Amelotin (Amtn) and Lamininβ3 subunit (Lamβ3), whereas type 4 collagen (Col4) mRNA were decreased. Immunocytochem. anal. showed that FDC-SP, AMTN, and Lamβ3 protein levels were increased in GE1 and Ca9-22 cells. Transient transfection analyses were performed using luciferase constructs including various lengths of human FDC-SP gene promoter, nifedipine increased luciferase activities of -345 and -948FDC-SP constructs. These results raise the possibility that the nifedipine-induced FDC-SP may be related to the mechanism responsible for gingival overgrowth does not occur at edentulous jaw ridges.

Odontology published new progress about Amelotins Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

Asante, Du-Bois published the artcileAnti-inflammatory, anti-nociceptive and antipyretic activity of young and old leaves of Vernonia amygdalina, SDS of cas: 21829-25-4, the main research area is Vernonia leaf anti inflammatory nociceptive antipyretic; Aspirin; Cold allodynia; Diclofenac; Edema; Mast cells; Paw withdrawal; Pyrexia; Vernonia amygdalina.

Both young and old leaves of Vernonia amygdalina (VA) are traditionally used to treat inflammation, pain and fever. However, the efficacy of young and old leaves for treating these ailments have not been compared till date. To ascertain the effect of young and old leaves of VA in managing inflammation, pain and fever. Both quant. and qual. phytochem. screening of ethanol extracts of young (EthYL) and old (EthOL) leaves of VA were performed. The anti-inflammatory activity of orally administered Et and EthOL (50-200 mg/kg) and Diclofenac (10 mg/kg) were evaluated in carrageenan-induced inflammation model in rats. Antipyretic activity of Et, EthOL and Aspirin (25 mg/kg) were assessed in the Baker’s yeast-induced pyrexia model. Anti-allodynic effect of both extracts were evaluated by inserting inflamed paws of rats in cold water. Antinociceptive property of the extracts were assessed using tail withdrawal and formalin-induced nociception test. Histopathol. examination of the paws was performed, in addition to formalin test to understand the possible mechanism of action of the extracts Neg. control rats received 2 mL/kg normal saline in all tests. The amount of flavonoids, alkaloids, tannins, and phenolics were significantly (p < 0.05) higher in EthOL than Et, while saponins were significantly higher (p < 0.05) in Et than EthOL. The antioxidant ability and total antioxidant capacity were significantly (p < 0.05) higher in Et than EthOL. However, this was significantly (p < 0.05) lower than the anti-oxidant activity of Ascorbic acid. A dose-dependent increase in anti-inflammatory, antipyretic and antinociceptive properties were observed in both Et and EthOL, similar to the standard drugs. Mast cell degranulation accompanied by vasodilatation and high leukocytosis were observed in the neg. control, but were markedly low in extract treated groups. Both extracts mediated their analgesic effect through opioidergic and nitric oxide pathways with Et addnl. implicating the muscarinic cholinergic system. Although both Et and EthOL alleviate inflammation, pyrexia and nociception, Et of VA was found to be more potent than EthOL. Biomedicine & Pharmacotherapy published new progress about Alkaloids Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

Yao, Jun published the artcileNifedipine inhibits oxidative stress and ameliorates osteoarthritis by activating the nuclear factor erythroid-2-related factor 2 pathway, Synthetic Route of 21829-25-4, the main research area is osteoarthritis nifedipine oxidative stress Nrf2; Inflammation; Nifedipine; Nrf2/HO-1 pathway; Osteoarthritis; Oxidative stress.

Nifedipine is a voltage-gated calcium channel inhibitor widely used in the treatment of hypertension. Nifedipine has been reported to have antioxidant and anti-apoptotic effects and promotes cell proliferation. However, the effects of nifedipine on oxidative stress and apoptosis in osteoarthritic (OA) chondrocytes are still unclear. In this study, we sought to investigate whether nifedipine alleviates oxidative stress and apoptosis in OA through nuclear factor erythroid-2-related factor 2 (Nrf2) activation. The cytotoxicity of nifedipine against human chondrocytes was detected using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) kit, whereas mRNA and protein expression levels were measured using reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting, resp. The oxidative stress level was analyzed by measuring reactive oxygen species (ROS), glutathione peroxidase (GSH-px), catalase (CAT) and superoxide dismutase (SOD) activities. The role of Nrf2 in the effect of nifedipine on OA was analyzed using an Nrf2 inhibitor brusatol (BR). The result showed that nifedipine inhibited the expression of matrix metalloprotein(MMP)-13, interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, cyclooxygenase (COX)-2, inducible nitric oxide (NO) synthase (iNOS), and prostaglandin E2 (PGE2), as well as reduced ROS production in human OA chondrocytes, which was partially reversed by BR. Nifedipine prevented cartilage degeneration and contributed to the expression of Nrf-2 in chondrocytes. These results indicate that nifedipine inhibited inflammation and oxidative stress in chondrocytes via activation of Nrf-2/HO-1 signaling.

Life Sciences published new progress about Aggrecans Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

Abuhassan, Qamar published the artcileSmall scale in vitro method to determine a bioequivalent equilibrium solubility range for fasted human intestinal fluid, COA of Formula: C18H19Cl2NO4, the main research area is bioequivalent equilibrium solubility human intestinal fluid; Aprepitant; Carvedilol; Fasted simulated intestinal fluid; Felodipine; Fenofibrate; Griseofulvin; Indomethacin; Intestinal solubility; Naproxen; Oral absorption; Phenytoin; Piroxicam; Probucol; Simulated intestinal fluid; Solubility; Tadalafil; Zafirlukast.

Drug solubility is a key parameter controlling oral absorption, but intestinal solubility is difficult to assess in vitro. Human intestinal fluid (HIF) aspirates can be applied but they are variable, difficult to obtain and expensive. Simulated intestinal fluids (SIF) are a useful surrogate but multiple recipes are available and the optimum is unknown. A recent study characterised fasted HIF aspirates using a multi-dimensional approach and determined nine bioequivalent SIF media recipes that represented over ninety percent of HIF compositional variability. In this study these recipes have been applied to determine the equilibrium solubility of twelve drugs (naproxen, indomethacin, phenytoin, piroxicam, aprepitant, carvedilol, zafirlukast, tadalafil, fenofibrate, griseofulvin, felodipine, probucol) previously investigated using a statistical design of experiment (DoE) approach. The bioequivalent solubility measurements are statistically equivalent to the previous DoE, enclose literature solubility values in both fasted HIF and SIF, and the solubility range is less than the previous DoE. These results indicate that the system is measuring the same solubility space as literature systems with the lower overall range suggesting improved equivalence to in vivo solubility, when compared to DoEs. Three drugs (phenytoin, tadalafil and griseofulvin) display a comparatively narrow solubility range, a behavior that is consistent with previous studies and related to the drugs’ mol. structure and properties. This solubility behavior would not be evident with single point solubility measurements. The solubility results can be analyzed using a custom DoE to determine the most statistically significant factor within the media influencing solubility This approach has a lower statistical resolution than a formal DoE and is not appropriate if determination of media factor significance for solubilisation is required. This study demonstrates that it is possible to assess the fasted intestinal equilibrium solubility envelope using a small number of bioequivalent media recipes obtained from a multi-dimensional anal. of fasted HIF. The derivation of the nine bioequivalent SIF media coupled with the lower measured solubility range indicate that the solubility results are more likely to reflect the fasted intestinal solubility envelope than previous DoE studies and highlight that intestinal solubility is a range and not a single value.

European Journal of Pharmaceutics and Biopharmaceutics published new progress about Bile salts Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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, COA of Formula: C18H19Cl2NO4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Zou, Xiaohan published the artcileBmK NSP, a new sodium channel activator from Buthus martensii Karsch, promotes neurite outgrowth in primary cultured spinal cord neurons, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is Buthus neurite spinal cord neuron; Neurite outgrowth; Scorpion toxin; Sodium channel.

In the current study, guided by a Ca2+ mobilization assay, we purified a new neuroactive peptide designated as BmK NSP (Buthus martensii Karsch neurite-stimulating peptide). The primary structure of BmK NSP was determined by Edman degradation BmK NSP concentration-dependently elevated intracellular Ca2+ concentration ([Ca2+]i) with an EC50 value of 4.18 μM in primary cultured spinal cord neurons (SCNs). Depletion of extracellular Ca2+ abolished BmK NSP-triggered Ca2+ response. Moreover, we demonstrated that BmK NSP-induced Ca2+ response was partially suppressed by the inhibitors of L-type Ca2+ channels, Na+-Ca2+ exchangers and NMDA receptors and was abolished by voltage-gated sodium channel (VGSC) blocker, tetrodotoxin. Whole-cell patch clamp recording demonstrated that BmK NSP delayed VGSC inactivation (EC50 = 1.10 μM) in SCNs. BmK NSP enhanced neurite outgrowth in a non-monotonic manner that peaked at âˆ?0 nM in SCNs. BmK NSP-promoted neurite outgrowth was suppressed by the inhibitors of L-type Ca2+ channels, NMDA receptors, and VGSCs. Considered together, these data demonstrate that BmK NSP is a new α-scorpion toxin that enhances neurite outgrowth through main routes of Ca2+ influx. Modulation of VGSC activity by α-scorpion toxin might represent a novel strategy to regulate the neurogenesis in SCNs.

Toxicon published new progress about Amino acids Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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

Modvig, Ida M. published the artcilePeptone-mediated glucagon-like peptide-1 secretion depends on intestinal absorption and activation of basolaterally located Calcium-Sensing Receptors, Application In Synthesis of 21829-25-4, the main research area is GLP1 glucagon like peptide1 calcium sensing receptor review; Amino acid sensing; Calcium-Sensing Receptor; glucagon-like peptide 1; peptide transporter 1; peptone.

Protein intake robustly stimulates the secretion of the incretin hormone, glucagon-like peptide-1 (GLP-1) but the mol. mechanisms involved are not well understood. In particular, it is unknown whether proteins stimulate secretion by activation of luminal or basolateral sensors. We characterized the mechanisms using a physiol. relevant model – the isolated perfused proximal rat small intestine. Intraluminal protein hydrolyzates derived from meat (peptone; 50 mg/mL) increased GLP-1 secretion 2.3-fold (from a basal secretion of 110 ± 28 fmol/min). The sensory mechanisms underlying the response depended on di/tripeptide uptake through Peptide Transporter 1 (PepT1) and subsequent basolateral activation of the amino acid sensing receptor, Calcium-Sensing Receptor (CaSR), since inhibition of PepT1 as well as CaSR both attenuated the peptone-induced GLP-1 response. Supporting this, intraluminal peptones were absorbed efficiently by the perfused intestine (resulting in increased amino acid concentrations in the venous effluent) and infusion of amino acids robustly stimulated GLP-1 secretion. Inhibitors of voltage-gated L-type Ca2+ channels had no effect on secretion suggesting that peptone-mediated GLP-1 secretion is not mediated by L-cell depolarization with subsequent opening of these channels. Specific targeting of CaSR could serve as a target to stimulate the endogenous secretion of GLP-1.

Physiological Reports published new progress about Amino acids Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 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