Month: December 2022

Ross, John H. published the artcileToxicity of 1,1′-alkyl-4,4′-bipyridylium salts in the rat, COA of Formula: C26H42Br2N2, the main research area is alkylbipyridylium toxicity; bipyridylium alkyl toxicity.

Viologens (I, R = Me or Ph; n = 1-7) were administered s.c. to female Sprague-Dawley rats to determine relative toxicities. I produced the spectrum of effects previously reported for paraquat and a focal necrosis at the injection site, nonemptying of the stomach, and adrenal enlargement. A LD of Pr, hexyl, or benzyl viologen often produced a yellow to red serous fluid in the pleural cavity. Many of the signs observed with I poisoning are similar to adrenal hormone effects which may be contributing to the toxicity.

Drug and Chemical Toxicology (1977) published new progress about Adrenal gland. 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, COA of Formula: C26H42Br2N2.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Sun, Lin published the artcileFelodipine-associated gingival overgrowth in a type 2 diabetic patient: a case report and literature review, Category: pyridine-derivatives, the main research area is type 2 diabetes gingival overgrowth felodipine; calcium channel blocker; drug-induced gingival overgrowth; felodipine.

Gingival overgrowth (GO) includes gingival enlargement and hyperplasia and may be induced by certain drugs, including calcium channel blockers (CCBs), particularly first-generation CCBs. However, to date, only few cases of GO induced by second- or third-generation CCBs have been reported. The present study reports on a case of a 48-yr-old diabetic male who was admitted to the First Hospital of Jilin University (Changchun, China) due to poor blood glucose control. This patient was diagnosed with GO. Review of the patient’s medical history revealed diagnoses of type 2 diabetes and hypertension, as well as the use of felodipine, a second-generation CCB, to control hypertension. The hypertensive drugs were replaced and the new drugs helped the patient control his blood glucose levels. Addnl., the patient was instructed on methods he could use to improve his oral hygiene, including rinsing of the teeth following each meal and increasing the frequency of tooth brushing per day. After 3 mo, the clin. symptoms of GO were relieved. The relevant literature was also reviewed to gain an improved understanding of the correlation between GO and CCBs, as well as diabetes and poor oral hygiene.

Experimental and Therapeutic Medicine published new progress about Adrenal gland. 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

Anonymous published the artcileA periodic table for liquid chromatography separation modes, Synthetic Route of 21829-25-4, the main research area is nifedipine captopril periodic table liquid chromatog physicochem property.

The increasing trend for non-expert users to undertake anal. measurements using an expanding range of chromatog. approaches can lead to the use of unsuitable separation methods and the generation of poor-quality data. Tech. Brief AMCTB Number 107 introduced liquid chromatog. and guidance on selection of the appropriate separation modality. This publication aims to provide a quick and easy to use educational tool for optimizing the mode of liquid chromatog. separation It will be of value to both expert and non-expert users across the natural, life and phys. sciences.

Analytical Methods published new progress about Hydrophobicity. 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

Alsufyani, Hadeel A. published the artcileRoles for α1-adrenoceptors during contractions by electrical field stimulation in mouse vas deferens, Related Products of pyridine-derivatives, the main research area is adrenoceptor elec field stimulation mouse; Adrenergic; Fertility; Muscle; Neuromuscular junction; Vas deferens; smooth.

We have investigated the relative roles of α1-adrenoceptors and purinoceptors in contractions to low and high frequency stimulation of the mouse vas deferens, in terms of the time course of responses. In sep. experiments, isometric contractile responses were obtained to 10 pulses at 1 Hz and 40 pulses at 10 Hz. Responses to 1 Hz stimulation consisted of a series of discrete peaks. The α1A-adrenoceptor antagonist RS100329 (10-9M-10-2M) significantly reduced the response to the first pulse, the α1D-adrenoceptor antagonist BMY7378 (10-7M-10-6M) significantly reduced the response to the first two pulses, and the non-selective α1-adrenoceptor antagonist prazosin (10-8M) reduced the response to the first 4 pulses at 1 Hz. Responses to 10 Hz stimulation consisted of an early peak response and a maintained plateau response. RS100329 significantly reduced the peak response but did not significantly affect the plateau response. Prazosin, significantly reduced both the peak and plateau responses. The α1A-adrenoceptor antagonist RS17053 in high concentrations reduced mainly the plateau response leaving a clear early peak response. The plateau response of contraction was almost abolished by the purinoceptor antagonist suramin. These results suggest that there is a relatively minor early α1D-adrenoceptor and a larger early α1A-adrenoceptor component to stimulationevoked contractions of mouse vas deferens, but the major α1-adrenoceptor component is revealed by prazosin to be α1B-adrenoceptor mediated. α1B-Adrenoceptor activation probably facilitates contractions mediated by other α1-adrenoceptors and by purinoceptors. These results suggest that combined non-selective α1-adrenoceptor blockade, particularly α1B-adrenoceptor blockade, in addition to P2X1-purinoceptor blockade is useful in reducing male fertility.

Korean Journal of Physiology & Pharmacology published new progress about Electric field. 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

Solomon, Samuel published the artcileInsights into the ameliorating ability of mesoporous silica in modulating drug release in ternary amorphous solid dispersion prepared by hot melt extrusion, HPLC of Formula: 72509-76-3, the main research area is mesoporous silica drug release solid dispersion hotmelt extrusion; Felodipine; Hotmelt Extrusion; Soluplus; Solvent less; Ternary dispersions.

In this work, the application of various mesoporous silica grades in the preparation of stabilized ternary amorphous solid dispersions of Felodipine using hot melt extrusion was explored. We have demonstrated the effectiveness of mesoporous silica in these dispersions without the need for any organic solvents i.e., no pre-loading or immersion steps required. The phys. and chem. properties, release profiles of the prepared formulations and the surface concentrations of the various mol. species were investigated in detail. Formulations containing 25 wt% and 50 wt% of Felodipine demonstrated enhanced stability and solubility of the drug substance compared to its crystalline counterpart. Based on the Higuchi model, ternary formulations exhibited a 2-step or 3-step release pattern which can be ascribed to the release of drug mols. from the organic polymer matrix and the external silica surface, followed by a release from the silica pore structure. According to the Korsmeyer-Peppas model, the release rate and release mechanism are governed by a complex quasi-Fickian release mechanism, in which multiple release mechanisms are occurring concurrently and consequently. Stability studies indicated that after 6 mo storage of all formulation at 30% RH and 20°C, Felodipine in all formulations remained stable in its amorphous state except for the formulation comprised of 40 wt% Syloid AL-1FP with a 50 wt% drug load.

European Journal of Pharmaceutics and Biopharmaceutics published new progress about Drug stability. 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, HPLC of Formula: 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Achim, Marcela published the artcilePreparation and in vitro evaluation of felodipineloaded poly(ε-caprolactone) microspheres: quality by design approach, Category: pyridine-derivatives, the main research area is felodipine polycaprolactone microsphere polydispersity index drug development.

Felodipine was encapsulated into poly(ε-caprolactone) microspheres by the emulsion solvent evaporation method by employing the Quality by Design (QbD) strategy. Based on a risk anal., the influence of 4 critical process parameters (type of stirrer, stirring rate, shape of mixing vessel, aqueous phase volume) on the critical quality attributes of the microspheres (size, polydispersity, entrapment efficiency (EE)), was evaluated by a full factorial exptl. design. The microspheres’ morphol. and felodipine in vitro release were also studied. The particles’ size ranged between 39.8 and 302.5μm, and the polydispersity index varied from 0.279 to 0.517. Felodipine EE was above 93.59%. SEM (SEM) anal. revealed spherical particles, with imperfections and micropores on the surface. The microspheres exhibited an extended release of felodipine over a period of 12 h. In conclusion, the QbD approach helped understand the process parameters and their impact on the quality profile in the development of felodipine-loaded microspheres.

Farmacia (Bucharest, Romania) published new progress about Drug discovery. 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

Ge, Kai published the artcileNovel Computational Approach by Combining Machine Learning with Molecular Thermodynamics for Predicting Drug Solubility in Solvents, Formula: C18H19Cl2NO4, the main research area is antipyrine benzamide doxofylline gefitinib thermodn machine learning.

In this work, a novel strategy that combined mol. thermodn. and machine learning was proposed to accurately predict the solubility of drugs in various solvents. The strategy was based on 16 mol. descriptors representing drug-drug interactions and drug-solvent interactions including phys. parameters, pure perturbed-chain statistical associating fluid theory (PC-SAFT) parameters of drugs and solvents, and mixing rules. These mol. descriptors were inputted into five machine learning algorithms [multiple linear regression (MLR), artificial neural network (ANN), random forest (RF), extremely randomized trees (ET), and support vector machine (SVM)] to train the predictive model. A single-hidden-layer neural network was finally determined as the predictive model for predicting the solubility of drugs in various solvents. The drug solubility in the generalization evaluation set has also been successfully predicted, which indicates the good prediction performance of the model. Three directions for improving the model were summarized as adding mol. descriptors of drug-solvent interactions in the water system and drug-drug interactions in the organic solvent system and expanding the dataset to adequately obtain the features of multiple drugs. These findings show that the proposed model has the capability of solubility prediction, which is expected to provide important information for drug development and drug solvent screening.

Industrial & Engineering Chemistry Research published new progress about Drug discovery. 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, Formula: C18H19Cl2NO4.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Wang, Zhangting published the artcileLiquorice extract and 18β-glycyrrhetinic acid protect against experimental pyrrolizidine alkaloid-induced hepatotoxicity in rats through inhibiting cytochrome P450-mediated metabolic activation, Quality Control of 21829-25-4, the main research area is nifidepine glycyrrhetinic acid hepatoprotectant CYP450 liver injury; 18β-glycyrrhetinic acid; competitive inhibition; cytochrome P450; metabolic activation; pyrrolizidine alkaloid.

Misuse of pyrrolizidine alkaloid (PA)-containing plants or consumption of PA-contaminated foodstuffs causes numerous poisoning cases in humans yearly, while effective therapeutic strategies are still limited. PA-induced liver injury was initiated by cytochrome P 450 (CYP)- mediated metabolic activation and subsequent formation of adducts with cellular proteins. Liquorice, a hepato-protective herbal medicine, is commonly used concurrently with PA-containing herbs in many compound traditional Chinese medicine formulas, and no PA-poisoning cases have been reported with this combination. The present study aimed to investigate hepato-protective effects of liquorice aqueous extract (EX) and 18β-glycyrrhetinic acid (GA, the primary bioactive constituent of liquorice) against PA-induced hepatotoxicity and the underlying mechanism. Histopathol. and biochem. anal. demonstrated that both single- and multiple-treatment of EX (500 mg/kg) or GA (50mg/kg) significantly attenuated liver damage caused by retrorsine (RTS, a representative hepatotoxic PA). The formation of pyrrole-protein adducts was significantly reduced by single- (30.3% reduction in liver; 50.8% reduction in plasma) and multiple- (32.5% reduction in liver; 56.5% reduction in plasma) treatment of GA in rats. Single- and multiple-treatment of EX also decreased the formation of pyrrole-protein adducts, with 30.2 and 31.1% reduction in rat liver and 51.8 and 53.1% reduction in rat plasma, resp. In addition, in vitro metabolism assay with rat liver microsomes demonstrated that GA reduced the formation of metabolic activation-derived pyrrole-glutathione conjugate in a dose-dependent manner with the estimated IC50 value of 5.07μM. Further mechanism study showed that GA inhibited activities of CYPs, especially CYP3A1, the major CYP isoform responsible for the metabolic activation of RTS in rats. Enzymic kinetic study revealed a competitive inhibition of rat CYP3A1 by GA. In conclusion, our findings demonstrated that both EX and GA exhibited significant hepato-protective effects against RTS-induced hepatotoxicity, mainly through the competitive inhibition of CYP-mediated metabolic activation of RTS.

Frontiers in Pharmacology published new progress about Detoxification. 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

Chen, Yinshan published the artcileEffect of molecular size and hydrogen bonding on three surface-facilitated processes in molecular glasses: Surface diffusion, surface crystal growth, and formation of stable glasses by vapor deposition, HPLC of Formula: 72509-76-3, the main research area is mol size hydrogen bonding surface diffusion; crystal growth stable glass vapor deposition.

Recent work has shown that diffusion and crystal growth can be much faster on the surface of mol. glasses than in the interior and that the enhancement effect varies with mol. size and intermol. hydrogen bonds (HBs). In a related phenomenon, some mols. form highly stable glasses when vapor-deposited, while others (notably those forming extensive HBs) do not. Here we examine all available data on these phenomena for quant. structure-property relations. For the systems that form no HBs, the surface diffusion coefficient Ds decreases with increasing mol. size d (d = Ω1/3, where Ω is the mol. volume); when evaluated at the glass transition temperature Tg, Ds decreases ∼5 orders of magnitude for 1 nm of increase in d. Assuming that center-of-mass diffusion is limited by the deepest part of the mol. in the surface-mobility gradient, these data indicate a mobility gradient in reasonable agreement with the Elastically Collective Nonlinear Langevin Equation theory prediction for polystyrene as disjointed Kuhn monomers. For systems of similar d, the Ds value decreases with the extent of intermol. HB, x (HB), defined as the fraction of vaporization enthalpy due to HB. For both groups together (hydrogen-bonded and otherwise), the Ds data collapse when plotted against d/[1 – x(HB)]; this argues that the HB effect on Ds can be described as a narrowing of the surface mobility layer by a factor [1 – x(HB)] relative to the van der Waals systems. Essentially the same picture holds for the surface crystal growth rate us. The kinetic stability of a vapor-deposited glass decreases with x(HB) but is not better organized by the combined variable d/[1 – x(HB)]. These results indicate that surface crystal growth depends strongly on surface diffusion, whereas the formation of stable glasses by vapor deposition may depend on other factors. (c) 2019 American Institute of Physics.

Journal of Chemical Physics published new progress about Crystal growth. 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, HPLC of Formula: 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Guan, Jian published the artcileSynergetic effect of nucleation and crystal growth inhibitor on in vitro-in vivo performance of supersaturable lacidipine solid dispersion, HPLC of Formula: 72509-76-3, the main research area is c nucleation crystal growth inhibitor supersaturable lacidipine solid dispersion; Gum arabic; Lacidipine; Solid dispersion; Soluplus; Supersaturation.

Limited supersaturation maintaining duration is the main challenge for amorphous solid dispersion design. Nucleation or crystal growth inhibitors may function in different ways but the combination use of nucleation and crystal growth inhibitors in supersaturated system is rarely explored. Thus, using Lacidipine (LCDP) as a Biopharmaceutical Classification System (BCS) II model drug, the aim of this study was to explore whether the combination use of nucleation and crystal growth inhibitors could provide a synergistic effect on the in vitro-in vivo performance of poorly water-soluble drugs. First of all, based on compatibility screening using solubility parameter (Δδ) and crystallization inhibition efficiency as criteria, soluplus (SOL) and gum arabic (GA) were selected as the most effective nucleation and crystal growth inhibitor resp. Thereafter, the supersaturated drug solutions were spray dried and characterized. The in vitro release, phys. stability as well as pharmacokinetic behavior were investigated. It was found that the combination use of SOL and GA did not present remarkable advantage in prolonging the supersaturation time in solution state. However, their synergistic effect in equilibrium solubility and dissolution enhancement was noticed at SOL/GA ratio 3:1, with 5-7 times higher dissolution rate observed for LCDP/SOL/GA based formulation compared with that of LCDP/SOL, which was maintained even after three months accelerated stability test under non-sink condition. Moreover, compared to the LCDP/SOL formulation, approx. 2.8 and 2.5-fold increase in the maximum plasma concentration (Cmax) and the area under the plasma-time curve (AUC0-∞) was achieved with LCDP/SOL/GA based formulation. Possible mechanism of the synergistic effect was elucidated, indicating GA may penetrate into SOL particles providing both electrostatic and steric stabilization. In conclusion, the combination use of screened nucleation and crystal growth inhibitors might be an efficient approach to design supersaturated drug delivery system.

International Journal of Pharmaceutics (Amsterdam, Netherlands) published new progress about Crystal growth. 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, HPLC of Formula: 72509-76-3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem