Category: pyridine-derivatives

Saboo, Sugandha published the artcileCongruent release of drug and polymer: A “”sweet spot”” in the dissolution of amorphous solid dispersions, Synthetic Route of 21829-25-4, the main research area is amorphous solid dispersion liquid phase separation drug congruent release; Amorphous solid dispersion; Congruent release; Dissolution; Liquid-liquid phase separation.

Liquid-liquid phase separation (LLPS) occurs following amorphous solid dispersion (ASD) dissolution when the drug concentration exceeds the “”amorphous solubility””, and is emerging as an important characteristic of formulations that may enhance the oral bioavailability of poorly soluble drugs. The purpose of this research was to identify criteria that impact the rate and extent of drug release and hence the occurrence or not of LLPS upon ASD dissolution The model polymer was poly (vinylpyrrolidone-co-vinyl acetate) (PVPVA). Nil-PVPVA and Cil-PVPVA ASDs with different drug loadings were prepared Surface area normalized dissolution rates of both the drug and the polymer from ASD tablets were studied. At a similar and relatively low drug loading (<20% weight/weight drug), dissolution of both Nil-PVPVA and Cil-PVPVA ASDs was found to switch from rapid, congruent (i.e., simultaneous) release of drug and polymer to incongruent release with slow release of drug. SEM (SEM) and micro-computed tomog. (micro-CT) showed the presence of characteristic ""pits"" on the surface of partially dissolved, incongruently releasing ASD tablets. This study demonstrates two important findings, firstly, a link between congruent release of drug and polymer and the occurrence of LLPS and secondly, the switch between congruent and incongruent release of drug and polymer is a result of competitive kinetics between phase separation and the release rate of ASD components with minimal influence from drug hydrophobicity for two structural analogs. Journal of Controlled Release published new progress about Crystals. 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

Wu, Haixi published the artcileCase report: concurrence of dermatomyositis and autoimmune blistering diseases: two case reports and a literature review, Recommanded Product: 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is prednisone methotrexate minocycline halometasone dermatomyositis autoimmune blistering disease; autoimmune blistering disease; bullous dermatomyositis; clinically amyopathic dermatomyositis; dermatomyositis; interstitial lung disease; malignancy.

Dermatomyositis (DM) is an idiopathic inflammatory myopathy primarily involving skin and muscles. Clin. amyopathic dermatomyositis (CADM), a subset of DM, presents with characteristic cutaneous manifestations without clin. evidence of myositis. Although rare, vesiculobullous eruptions could develop in DM patients. Such ‘bullous DM’ is commonly considered a sign of internal malignancy. However, some cases with similar presentations were diagnosed as autoimmune blistering disease eventually. Herein, we reported two cases of CADM with autoimmune blisters formed. Case 1 presented with vesicles and was diagnosed with CADM initially. However, this patient developed blisters again years later and was diagnosed with ‘pemphigus foliaceous’ (PF) accordingly. Case 2, with a history of nasopharyngeal carcinoma and CADM, developed bullous pemphigoid several days after using a heat patch on her abdomen. The association between disease occurrence and local skin damage might provide more evidence to support the ‘epitope spreading’ hypothesis. Moreover, we reviewed related literature and discussed the differences between the two disease entities in clin. presentations, pathogenesis, therapy, and the risk of complications.

Frontiers in Immunology published new progress about Abdomen. 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, Recommanded Product: 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Yang, Tingting published the artcileL- and T-type calcium channels control aldosterone production from human adrenals, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is TTAP2 nifedipine calcium aldosterone human adrenal; L-type calcium channels; T-type calcium channels; aldosterone secretion; primary aldosteronism.

Aldosterone, which plays a key role in the regulation of blood pressure, is produced by zona glomerulosa (ZG) cells of the adrenal cortex. Exaggerated overproduction of aldosterone from ZG cells causes primary hyperaldosteronism. In ZG cells, calcium entry through voltage-gated calcium channels plays a central role in the regulation of aldosterone secretion. Previous studies in animal adrenals and human adrenal adrenocortical cell lines suggest that the T-type but not the L-type calcium channel activity drives aldosterone production However, recent clin. studies show that somatic mutations in L-type calcium channels are the second most prevalent cause of aldosterone-producing adenoma. Our objective was to define the roles of T and L-type calcium channels in regulating aldosterone secretion from human adrenals. We find that human adrenal ZG cells mainly express T-type CaV3.2/3.3 and L-type CaV1.2/1.3 calcium channels. TTA-P2, a specific inhibitor of T-type calcium channel subtypes, reduced basal aldosterone secretion from acutely prepared slices of human adrenals. Surprisingly, nifedipine, the prototypic inhibitor of L-type calcium channels, also decreased basal aldosterone secretion, suggesting that L-type calcium channels are active under basal conditions. In addition, TTA-P2 or nifedipine also inhibited aldosterone secretion stimulated by angiotensin II- or elevations in extracellular K+. Remarkably, blockade of either L- or T-type calcium channels inhibits basal and stimulated aldosterone production to a similar extent. Low concentrations of TTA-P2 and nifedipine showed additive inhibitory effect on aldosterone secretion. We conclude that T- and L-type calcium channels play equally important roles in controlling aldosterone production from human adrenals.

Journal of Endocrinology published new progress about Adenoma. 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

Mary, Sheon published the artcileSalt loading decreases urinary excretion and increases intracellular accumulation of uromodulin in stroke-prone spontaneously hypertensive rats, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is SHRSP salt urinary excretion uromodulin intracellular accumulation; Salt; Tamm Horsfall protein; blood pressure; renal physiology; salt-sensitive hypertension.

Uromodulin (UMOD) is the most abundant renal protein secreted into urine by the thick ascending limb (TAL) epithelial cells of the loop of Henle. Genetic studies have demonstrated an association between UMOD risk variants and hypertension. We aimed to dissect the role of dietary salt in renal UMOD excretion in normotension and chronic hypertension. Normotensive Wistar-Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) (n = 8/sex/strain) were maintained on 1% NaCl for 3 wk. A subset of salt-loaded SHRSP was treated with nifedipine. Salt-loading in SHRSP increased blood pressure (δSBP 35 ± 5 mmHg, P<0.0001) and kidney injury markers such as kidney injury marker-1 (KIM-1; fold change, FC 3.4; P = 0.003), neutrophil gelatinase-associated lipocalin (NGAL; FC, 2.0; P = 0.012) and proteinuria. After salt-loading there was a reduction in urinary UMOD excretion in WKY and SHRSP by 26 and 55% resp., compared with baseline. Nifedipine treatment reduced blood pressure (BP) in SHRSP, however, did not prevent salt-induced reduction in urinary UMOD excretion. In all experiments, changes in urinary UMOD excretion were dissociated from kidney UMOD protein and mRNA levels. Colocalization and ex-vivo studies showed that salt-loading increased intracellular UMOD retention in both WKY and SHRSP. Our study provides novel insights into the interplay among salt, UMOD, and BP. The role of UMOD as a cardiovascular risk marker deserves mechanistic reappraisal and further investigations based on our findings. Clinical Science published new progress about Alleles. 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

Hemati, Tahereh published the artcileActivation of L-type calcium channels and attenuation of oxidative stress are involved in the improving effect of methyl jasmonate on learning and memory and its anxiolytic property in rats, Related Products of pyridine-derivatives, the main research area is anxiety learning oxidative stress calcium channel methyl jasmonate.

The present study was designed to evaluate the effect of plant bioactive compound Me jasmonate on learning and memory, anxiety-like behaviors, and brain oxidative stress in rats. Therefore, we investigated the potential role of L-type calcium channel on Me jasmonate effects. The animals were intracerebroventriculary (i.c.v.) injected with different doses of Me jasmonate (0.5, 2.5, and 5μg/rat). L-type calcium channel blocker (nifedipine 5μg/rat, i.c.v.) was injected 30 min before Me jasmonate (5μg/rat). Shuttle box apparatus was used to evaluate passive avoidance memory. Anxiety-like behaviors were assessed by open field and elevated plus maze tests. Lastly, oxidative stress-related indexes were assessed in hippocampus and prefrontal cortex. The data showed that Me jasmonate dose-dependently could improve passive avoidance learning and memory and reduce anxiogenic behaviors. The Me jasmonate effects were significantly prevented by nifedipine. Furthermore, central microinjection of Me jasmonate significantly decreased hydrogen peroxide concentration, and increased reactive oxygen species scavenger activity (catalase and peroxide enzymes) in rats’ hippocampus as well as prefrontal cortex. Indeed, the results indicated that the beneficial effects of Me jasmonate on learning and memory and anxiety might be partly associated with L-type calcium channel and partly on the inhibition of oxidant indexes.

Behavioural Pharmacology published new progress about Anxiety. 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

Hayashi, Tokumasa published the artcileProperties of SK3 channel-expressing PDGFRα (+) cells in the rodent urinary bladder, COA of Formula: C17H18N2O6, the main research area is PDGFRalpha vimentin channelDSM contraction membrane hyperpolarization; Interstitial cell; P2Y receptor; Platelet-derived growth factor receptor-α (PDGFRα); Small-conductance calcium-activated potassium (SK3) channel; Urinary bladder.

Localisation of platelet-derived growth factor receptor-α (PDGFRα) (+) cells expressing small-conductance Ca2+-activated K+ (SK3) channels in the urinary bladder was investigated, while putative roles of SK3 (+) PDGFRα (+) cells in suppressing detrusor smooth muscle (DSM) spontaneous activity were explored. In guinea-pig bladder, immunohistochem. for SK3 channels, PDGFRα or vimentin was examined, as were the effects of purinergic agonists on spontaneous phasic contractions (SPCs). In bladder of PDGFRα-GFP mice, the effects of purinergic agonists on intracellular Ca2+ signaling in PDGFRα (+) cells or DSM cells in situ and SPCs were investigated. SK3 (+) cells co-expressing PDGFRα or vimentin were distributed in DSM bundles but not inter-bundle spaces or lamina propria. SK3 (+) cells had a stellate- or spindle-shape cell body extending processes. MRS2365 (100 nM or 1μM), a P2Y1 agonist, caused a transient contraction without inhibiting SPCs in both DSM and lamina propria. In PDGFRα-GFP mice bladder, MRS2365, (100 nM), ADP (100μM) or ATP (100μM) increased the Ca2+ level of PDGFRα (+) cells without suppressing spontaneous Ca2+ transients in neighboring DSM cells, and also failed to suppress SPCs. Preferential localisation of SK3 pos. PDGFRα (+) cells in DSM bundles appears to indicate their functional interaction with DSM cells. However, increases in Ca2+ level of PDGFRα (+) cells upon purinergic stimulation are not associated with the inhibition of Ca2+ or contractile activity in DSM cells. Thus, it is unlikely that the SK3-dependent hyperpolarization generated in SK3 expressing PDGFRα (+) cells is transmitted to DSMs to suppress their excitability.

European Journal of Pharmacology published new progress about Bladder. 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

Salehi, Niloufar published the artcileHierarchical Mass Transfer Analysis of Drug Particle Dissolution, Highlighting the Hydrodynamics, pH, Particle Size, and Buffer Effects for the Dissolution of Ionizable and Nonionizable Drugs in a Compendial Dissolution Vessel, Recommanded Product: 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is pharmaceutical particle pH dissolution; bicarbonate buffer; computer-aided drug design; dissolution; in vitro model; mathematical model; solubility.

Dissolution is a crucial process for the oral delivery of drug products. Before being absorbed through epithelial cell membranes to reach the systemic circulation, drugs must first dissolve in the human gastrointestinal (GI) tract. In vivo and in vitro dissolutions are complex because of their dependency upon the drug physicochem. properties, drug product, and GI physiol. properties. However, an understanding of this process is critical for the development of robust drug products. To enhance our understanding of in vivo and in vitro dissolutions, a hierarchical mass transfer (HMT) model was developed that considers the drug properties, GI fluid properties, and fluid hydrodynamics. The key drug properties include intrinsic solubility, acid/base character, pKa, particle size, and particle polydispersity. The GI fluid properties include bulk pH, buffer species concentration, fluid shear rate, and fluid convection. To corroborate the model, in vitro dissolution experiments were conducted in the USP (USP) 2 dissolution apparatus A weakly acidic (ibuprofen), a weakly basic (haloperidol), and a nonionizable (felodipine) drug were used to study the effects of the acid/base character, pKa, and intrinsic solubility on dissolution 900 mL of 5 mM bicarbonate and phosphate buffers at pH 6.5 and 37°C was used to study the impact of the buffer species on drug dissolution To investigate the impacts of fluid shear rate and convection, the apparatus was operated at different impeller rotational speeds. Moreover, presieved ibuprofen particles with different average diameters were used to investigate the effect of particle size on drug dissolution In vitro experiments demonstrate that the dissolution rates of both the ionizable compounds used in this study were slower in bicarbonate buffer than in phosphate buffer, with the same buffer concentration, because of the lower interfacial buffer capacity, a unique behavior of bicarbonate buffer. Therefore, using surrogates (i.e., 50 mM phosphate) for bicarbonate buffer for biorelevant in vitro dissolution testing may overestimate the in vivo dissolution rate for ionizable drugs. Model simulations demonstrated that, assuming a monodisperse particle size when modeling, dissolution may overestimate the dissolution rate for polydisperse particle size distributions. The hydrodynamic parameters (maximum shear rate and fluid velocity) under in vitro conditions in the USP 2 apparatus under different rotational speeds are orders of magnitude higher compared to the in vivo situation. The inconsistencies between the in vivo and in vitro drug dissolution hydrodynamic conditions may cause an overestimation of the dissolution rate under in vitro conditions. The in vitro dissolution data supported the accuracy of the HMT for drug dissolution This is the first drug dissolution model that incorporates the effect of the bulk pH and buffer concentration on the interfacial drug particle solubility of ionizable compounds, combined with the medium hydrodynamics effect (diffusion, convection, shear, and confinement components), and drug particle size distribution.

Molecular Pharmaceutics published new progress about Buffers. 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, Recommanded Product: 3-Ethyl 5-methyl 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Weidmann, Klaus published the artcile2-[(2-Pyridylmethyl)sulfinyl]-1H-thieno[3,4-d]imidazoles. A novel class of gastric H+/K+-ATPase inhibitors, SDS of cas: 149489-32-7, the main research area is pyridylmethylsulfinylthienoimidazole preparation inhibitor ATPase; stomach acid secretion inhibitor pyridylmethylsulfinylthienoimidazole; gastric acid secretion inhibitor pyridylmethylsulfinylthienoimidazole.

2-[(2-Pyridylmethyl)sulfinyl]thienoimidazoles I (R = H, Me, Ac, Ph, MeO2C, 4-MeOC6H4; R1 = H, Me, MeO2C; R2 = H, Me, MeO, F, Cl, Br, fluoroalkoxy; R3 = H, Me, alkoxy, and substituted alkoxy, benzyloxy, and phenoxy; R4 = H, Me, MeO, F, Cl, Br) and II (R, R1 = H, MeO2C; R2 = H, MeO) were synthesized and investigated as potential inhibitors of gastric H+/K+-ATPase. The [3,4-d] isomers of the two possible thienoimidazole series were found to be potent inhibitors of gastric acid secretion in vitro and in vivo. Structure-activity relationships indicate that especially lipophilic alkoxy, benzyloxy, and phenoxy substituents with addnl. electron-demanding properties in the 4-position of the pyridine moiety combined with an unsubstituted thieno[3,4-d]imidazole lead to highly active compounds with a favorable chem. stability. Various substitution patterns in the thieno[3,4-d]imidazole moiety result in lower biol. activity. Saviprazle [HOE 731, I; R-R2 = R4 = H, R3 = F3C(CF2)2CH2O] was selected for further development and is currently undergoing clin. evaluation. Comprehensive pharmacol. studies indicate a pharmacodynamic profile different to omeprazole, the first H+/K+-ATPase blocker introduced on the market.

Journal of Medicinal Chemistry published new progress about Stomach. 149489-32-7 belongs to class pyridine-derivatives, name is 2-(Chloromethyl)-3-fluoropyridine, and the molecular formula is C6H5ClFN, SDS of cas: 149489-32-7.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Bhunia, Sudeshna published the artcileNew approaches suggest term and preterm human fetal membranes may have distinct biomechanical properties, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is term preterm human fetal membrane biomech property.

Preterm prelabour rupture of membranes is the leading cause of preterm birth and its associated infant mortality and morbidity. However, its underlying mechanism remains unknown. We utilized two novel biomech. assessment techniques, ball indentation and Optical Coherence Elastog. (OCE), to compare the mech. properties and behaviors of term (≥ 37 wk) and preterm (33-36 wk) human fetal membranes from ruptured and non-ruptured regions. We defined the expression levels of collagen, sulfated glycosaminoglycans (sGAG), matrix metalloproteinase (MMP-9, MMP-13), fibronectin, and interleukin-1β (IL-1β) within membranes by biochem. anal., immunohistochem. staining and Western blotting, both with and without simulated fetal movement forces on membrane rupture with a new loading system. Preterm membranes showed greater heterogeneity in mech. properties/behaviors between ruptured and non-ruptured regions compared with their term counterparts (displacement rate: 36% vs. 15%; modulus: 125% vs. 34%; thickness: 93% vs. 30%; collagen content: 98% vs. 29%; sGAG: 85% vs 25%). Furthermore, simulated fetal movement forces triggered higher MMP-9, MMP-13 and IL-1β expression in preterm than term membranes, while nifedipine attenuated the observed increases in expression. In conclusion, the distinct biomech. profiles of term and preterm membranes and the abnormal biochem. expression and activation by external forces in preterm membranes may provide insights into mechanisms of preterm rupture of membranes.

Scientific Reports published new progress about Amnion. 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

Zadymova, Natalia M. published the artcileMicroemulsions and microheterogeneous microemulsion-based polymeric matrices for transdermal delivery of lipophilic drug (Felodipine), Application In Synthesis of 72509-76-3, the main research area is microemulsion polymeric matrix transdermal drug delivery felodipine.

Transdermal administration of drugs is more effective than traditional methods: metabolism of a drug in the gastrointestinal tract and liver is excluded, and its constant concentration in blood is provided. In most cases, the main part of the transdermal patch (TP) is a polymer film (matrix) with good adhesion to skin, which contains a skin permeability enhancer (SPE) and a drug. Types of TPs differ in a way of drug incorporating into the matrix. In this work, a new type of polymer matrixes for the delivery of lipophilic drugs based on microemulsions is developed. An optimized direct microemulsion (IV type according to Winsor) is obtained; practically, all its components are SPEs. Microemulsion (ME) type is confirmed by conductometry and dynamic light-scattering methods. Solubilization capacity of ME in relation to the antihypertensive drug felodipine (FEL) is studied. This drug is characterized by poor water solubility and, consequently, by low bioavailability at oral administration (âˆ?15%). FEL solubility in ME exceeds its solubility in water by 2.2 × 104 times. ME efficiency as a carrier of FEL is shown using Franz diffusion cell and UV spectroscopy. The FEL-loaded microemulsion was used as the dispersed phase of the emulsion, and the dispersion medium of the emulsion was a solution of polymer adhesive (a mixture of polyisobutylenes with different mol. weights and polybutene) in heptane with optimized rheol. properties. This emulsified ME (i.e., inverse emulsion) is served as a basis for the microheterogeneous polymer matrix, which provides FEL release at a constant target rate during the day.

Colloid and Polymer Science published new progress about Antihypertensives. 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 In Synthesis of 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem