Category: pyridine-derivatives

Alshargabi, Rehab published the artcileSPOCK1 is a novel inducer of epithelial to mesenchymal transition in drug-induced gingival overgrowth, Synthetic Route of 21829-25-4, the main research area is gingival overgrowth SPOCK1 cancerous lesion epithelial to mesenchymal transition.

Abstract: Few studies have investigated the role of extracellular-matrix proteoglycans in the pathogenesis of drug-induced gingival overgrowth (DIGO). SPOCK1 is an extracellular proteoglycan that induces epithelial to mesenchymal transition (EMT) in several cancer cell lines and exhibits protease-inhibitory activity. However, the role of SPOCK1 in non-cancerous diseases such as DIGO has not been well-addressed. We demonstrated that the expression of SPOCK1, TGF-β1, and MMP-9 in calcium channel blocker-induced gingival overgrowth is higher than that in non-overgrowth tissues. Transgenic mice overexpressing Spock1 developed obvious gingival-overgrowth and fibrosis phenotypes, and pos. correlated with EMT-like changes. Furthermore, in vitro data indicated a tri-directional interaction between SPOCK1, TGF-β1, and MMP-9 that led to gingival overgrowth. Our study shows that SPOCK1 up-regulation in a noncancerous disease and SPOCK1-induced EMT in gingival overgrowth occurs via cooperation and crosstalk between several potential signaling pathways. Therefore, SPOCK1 is a novel therapeutic target for gingival overgrowth and its expression is a potential risk of EMT induction in cancerous lesions.

Scientific Reports published new progress about Calcium channel blockers. 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

Chen, Ying published the artcileSperm motility modulated by Trpv1 regulates zebrafish fertilization, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is Trpv1 mutation fertilization sperm motility zebrafish; Fertilization; Sperm motility; Trpv1; Zebrafish.

By responding to environmental and intracellular stimuli, ion channels play critical roles in sperm function regulation. Although the importance of ion channel in male reproduction has drawn increasing attention in many species, the knowledge about ion channels in zebrafish sperm is limited. Here, we show zebrafish sperm motility could be suppressed by general calcium channel blockers rather than by general potassium channel blockers. Further investigation found that sperm motility was not only suppressed by antagonist for the transient receptor potential vanilloid channel, subtype 1 (Trpv1), but also restored by its agonist, suggesting functional presence of Trpv1 in zebrafish spermatozoa. As a consequence, the suppression of sperm motility by Trpv1 antagonist could reduce in vitro fertilization rate. Western blot and immunofluorescence anal. proved that Trpv1 was mainly distributed in the neck and tail regions of zebrafish sperm. Addnl., neither antagonist nor agonist of Trpv1 exhibited effect on the motility of trpv1-/- zebrafish sperm. To our knowledge, this is one of the limited studies showing the importance of ion channels in regulating zebrafish sperm function, and may enrich our understanding on male reproductive physiol. of zebrafish and offer novel regulatory target for fish breeding and sperm cryopreservation.

Theriogenology published new progress about Calcium channel blockers. 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

Wang, Dongdong published the artcilePopulation pharmacokinetics of tacrolimus in pediatric refractory nephrotic syndrome and a summary of other pediatric disease models, Quality Control of 72509-76-3, the main research area is tacrolimus pediatric refractory nephrotic syndrome pharmacokinetics; nonlinear mixed-effects modeling; pediatric refractory nephrotic syndrome; population pharmacokinetics; tacrolimus; therapeutic drug monitoring.

Different tacrolimus (TAC) population pharmacokinetic (PPK) models have been established in various pediatric disease populations. However, a TAC PPK model for pediatric refractory nephrotic syndrome (PRNS) has not been well characterized. The current study aimed to establish a TAC PPK model in Chinese PRNS and provide a summary of previous literature concerning TAC PPK models in different pediatric diseases. A total of 147 TAC conventional therapeutic drug monitoring (TDM) data from multiple blood samples obtained from 65 Chinese patients with PRNS were characterized using nonlinear mixed-effects modeling. The impacts of demog. features, biol. characteristics and drug combination were evaluated. Model validation was assessed using the bootstrap method. A one-compartment model with first-order absorption and elimination was determined to be the most suitable model for TDM data in PRNS. The absorption rate constant (Ka) was set at 4.48 h-1. The typical values of apparent oral clearance (CL/F) and apparent volume of distribution (V/F) in the final model were 5.46 l/h and 57.1 l, resp. The inter-individual variability of CL/F and V/F were 22.2 and 0.2%, resp. The PPK equation for TAC was: CL/F = 5.46 × exponential function (EXP)(0.0323 × age) × EXP(-0.359 × cystatin-C) × EXP(0.148 × daily dose of TAC). No significant effects of covariates on V/F were observed In conclusion, the current study developed and validated the first TAC PPK model for patients with PRNS. The study also provided a summary of previous literature concerning other TAC PPK models in different pediatric diseases.

Experimental and Therapeutic Medicine 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, Quality Control of 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Walsh, Katie published the artcileAmination of Heteroaryl Chlorides: Palladium Catalysis or SNAr in Green Solvents?, Product Details of C9H11N3O3, the main research area is pyrimidine pyrazine quinazoline preparation; heteroaryl chloride amine SNAr arylation water potassium fluoride; amination; aromatic substitution; green chemistry; nucleophilic substitution.

The reaction of heteroaryl chlorides in the pyrimidine, pyrazine and quinazoline series with amines in water in the presence of KF results in a facile SNAr reaction and N-arylation products, e. g., I. The reaction is less satisfactory with pyridines unless an addnl. electron-withdrawing group is present. The results showed that the transition-metal-free SNAr reaction not only compares favorably to palladium-catalyzed coupling reactions but also operates under environmentally acceptable (“”green””) conditions in terms of the base and solvent.

ChemSusChem published new progress about Aryl chlorides Role: RCT (Reactant), RACT (Reactant or Reagent). 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

Idoux, Romane published the artcileDivalent cations permeation in a Ca2+ non-conducting skeletal muscle dihydropyridine receptor mouse model, SDS of cas: 21829-25-4, the main research area is calcium dihydropyridine receptor divalent cation skeletal muscle; Ca(V)1.1; Dihydropyridine receptor; Skeletal muscle fiber; Voltage clamp; Voltage-gated Ca(2+)channel.

In response to excitation of skeletal muscle fibers, trains of action potentials induce changes in the configuration of the dihydropyridine receptor (DHPR) anchored in the tubular membrane which opens the Ca2+ release channel in the sarcoplasmic reticulum membrane. The DHPR also functions as a voltage-gated Ca2+ channel that conducts L-type Ca2+ currents routinely recorded in mammalian muscle fibers, which role was debated for more than four decades. Recently, to allow a closer look into the role of DHPR Ca2+ influx in mammalian muscle, a knock-in (ki) mouse model (ncDHPR) carrying mutation N617D (adjacent to domain II selectivity filter E) in the DHPRα1S subunit abolishing Ca2+ permeation through the channel was generated [Dayal et al., 2017]. In the present study, the Mn2+ quenching technique was initially intended to be used on voltage-clamped muscle fibers from this mouse to determine whether Ca2+ influx through a pathway distinct from DHPR may occur to compensate for the absence of DHPR Ca2+ influx. Surprisingly, while N617D DHPR muscle fibers of the ki mouse do not conduct Ca2+, Mn2+ entry and subsequent quenching did occur because Mn2+ was able to permeate and produce L-type currents through N617D DHPR. N617D DHPR was also found to conduct Ba2+ and Ba2+ currents were strongly blocked by external Ca2+. Ba2+ permeation was smaller, current kinetics slower and Ca2+ block more potent than in wild-type DHPR. These results indicate that residue N617 when replaced by the neg. charged residue D is suitably located at entrance of the pore to trap external Ca2+ impeding in this way permeation. Because Ba2+ binds with lower affinity to D, Ba2+ currents occur, but with reduced amplitudes as compared to Ba2+ currents through wild-type channels. We conclude that mutations located outside the selectivity filter influence channel permeation and possibly channel gating in a fully differentiated skeletal muscle environment.

Cell Calcium published new progress about Cell membrane. 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

Negi, Shigeto published the artcileSynthesis of (2R)-1-(4-chloro-2-pyridyl)-2-(2-pyridyl)ethylamine. A selective oxime reduction and crystallization-induced asymmetric transformation, COA of Formula: C7H6ClNO2, the main research area is pyridylethylamine preparation stereoselective crystallization; ethylamine chloropyridyl pyridyl preparation; oxime selective reduction.

Reduction of 1-(4-chloro-2-pyridyl)-2-(2-pyridyl)ethanone oxime using Zn in CF3CO2H gave the corresponding racemic pyridylethylamine I in excellent yield without reductive removal of the Cl atom. A subsequent diastereomeric crystallization of I with an optically active cis-cyclohexanecarboxylic acid derivative in the presence of a catalytic amount of 3,5-dichlorosalicylaldehyde gave the desired (R)-amine in 42% yield via a crystallization-induced asym. transformation.

Synthesis published new progress about Reduction, chemoselective. 24484-93-3 belongs to class pyridine-derivatives, name is Methyl 4-chloropicolinate, and the molecular formula is C7H6ClNO2, COA of Formula: C7H6ClNO2.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Peng, Chiung-Chi published the artcileNifedipine upregulates ATF6-α, caspases -12, -3, and-7 implicating lipotoxicity-associated renal ER stress, HPLC of Formula: 21829-25-4, the main research area is endoplasmic reticular stress nifedipine ATF6 lipotoxicity; ATF6α, lipotoxicity; ER stress; chronic kidney disease; nifedipine.

Nifedipine (NF) is reported to have many beneficial effects in antihypertensive therapy. Recently, we found that NF induced lipid accumulation in renal tubular cells. Palmitic acid-induced renal lipotoxicity was found to be partially mediated by endoplasmic reticular (ER) stress, while it can also be elicited by NF in kidney cells; we examined the induction of suspected pathways in both in vitro and in vivo models. NRK52E cells cultured in high-glucose medium were treated with NF (30μM) for 24-48 h. ER stress-induced lipotoxicity was explored by staining with thioflavin T and Nile red, transmission electron microscopy, terminal uridine nick-end labeling, and Western blotting. ER stress was also investigated in rats with induced chronic kidney disease (CKD) fed NF for four weeks. NF induced the production of unfolded protein aggregates, resulting in ER stress, as evidenced by the upregulation of glucose-regulated protein, 78 kDa (GRP78), activating transcription factor 6α (ATF6α), C/EBP-homologous protein (CHOP), and caspases-12, -3, and -7. In vitro early apoptosis was more predominant than late apoptosis. Most importantly, ATF6α was confirmed to play a unique role in NF-induced ER stress in both models. CKD patients with hypertension should not undergo NF therapy. In cases where it is required, alleviation of ER stress should be considered to avoid further damaging the kidneys.

International Journal of Molecular Sciences published new progress about Apoptosis. 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

Lee, A. Reum published the artcileLercanidipine synergistically enhances bortezomib cytotoxicity in cancer cells via enhanced endoplasmic reticulum stress and mitochondrial Ca2+ overload, Application of 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is breast cancer lercanidipine bortezomib cytotoxicity endoplasmic reticulum mitochondria calcium; ER stress; bortezomib; lercanidipine; mitochondrial Ca2+ overload; paraptosis.

The proteasome inhibitor (PI), bortezomib (Btz), is effective in treating multiple myeloma and mantle cell lymphoma, but not solid tumors. In this study, we show for the first time that lercanidipine (Ler), an antihypertensive drug, enhances the cytotoxicity of various PIs, including Btz, carfilzomib, and ixazomib, in many solid tumor cell lines by inducing paraptosis, which is accompanied by severe vacuolation derived from the endoplasmic reticulum (ER) and mitochondria. We found that Ler potentiates Btz-mediated ER stress and ER dilation, possibly due to misfolded protein accumulation, in MDA-MB 435S cells. In addition, the combination of Btz and Ler triggers mitochondrial Ca2+ overload, critically contributing to mitochondrial dilation and subsequent paraptotic events, including mitochondrial membrane potential loss and ER dilation. Taken together, our results suggest that a combined regimen of PI and Ler may effectively kill cancer cells via structural and functional perturbations of the ER and mitochondria.

International Journal of Molecular Sciences published new progress about Antitumor agents. 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

Choi, Peter J. published the artcileSynthesis and evaluation of analogues of the tuberculosis drug bedaquiline containing heterocyclic B-ring units, HPLC of Formula: 71255-09-9, the main research area is bedaquiline analog antituberculosis thiophene furan pyridine; mol structure biol activity; Bedaquiline; Bedaquiline analogues; Drug development; Tuberculosis.

Analogs of bedaquiline (I) where the Ph B-unit was replaced with monocyclic heterocycles of widely differing lipophilicity (thiophenes, furans, pyridines) were synthesized and evaluated. While there was an expected broad pos. correlation between lipophilicity and anti-TB activity, the 4-pyridyl derivatives appeared to have an addnl. contribution to antibacterial potency. The majority of the compounds were (desirably) more polar and had higher rates of clearance than bedaquiline, and showed acceptable oral bioavailability, but there was only limited (and unpredictable) improvement in their hERG liability.

Bioorganic & Medicinal Chemistry Letters published new progress about Pyridines Role: PAC (Pharmacological Activity), RCT (Reactant), SPN (Synthetic Preparation), THU (Therapeutic Use), BIOL (Biological Study), RACT (Reactant or Reagent), PREP (Preparation), USES (Uses). 71255-09-9 belongs to class pyridine-derivatives, name is 2-Methoxynicotinaldehyde, and the molecular formula is C7H7NO2, HPLC of Formula: 71255-09-9.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Schlosser, Manfred published the artcileThe reactivity of 2-fluoro- and 2-chloropyridines toward sodium ethoxide: Factors governing the rates of nucleophilic (het)aromatic substitutions, Related Products of pyridine-derivatives, the main research area is reactivity fluoropyridine chloropyridine sodium ethoxide nucleophilic aromatic heteroaromatic substitution.

The relative displacement rates of the halide substituent from 2-fluoro- and 2-chloropyridines by EtONa in EtOH at +25° were assessed by competition kinetics. The 2-fluoropyridine reacts 320 times faster than the chloro analog. A CF3 group increases the reactivity more than single halogen atoms do, whatever the element, and the latter are superior to Me3Si groups. Substituents accommodated at the 4-position operate through their inductive effect, whereas at the 3-position, this action may be attenuated by steric hindrance. Almost all 5-substituents enhance the rate of the nucleophilic substitution occurring at the 2-position. The sole exception concerns the F-atom at the 5-position which retards the reaction, presumably by lone-pair/lone-pair repulsion with the neg. charge building up at the central C-atom of the intermediate Meisenheimer complex. The substituent effects are additive. Therefore, by using the increments derived from the present work, the rates of future reactions should be predictable with fair accuracy.

Helvetica Chimica Acta published new progress about Ethoxylation kinetics. 42144-78-5 belongs to class pyridine-derivatives, name is 2-Chloro-6-ethoxypyridine, and the molecular formula is C7H8ClNO, Related Products of pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem