Month: December 2022

Liu, Lei published the artcileWater-Resistant Drug-Polymer Interaction Contributes to the Formation of Nano-Species during the Dissolution of Felodipine Amorphous Solid Dispersions, Synthetic Route of 72509-76-3, the main research area is amorphous solid dispersion; drug−polymer interaction; intrinsic dissolution; nano-species; water resistant.

Drug-polymer interactions are of great importance in amorphous solid dispersion (ASD) formulation for both dissolution performance and phys. stability considerations. In this work, three felodipine ASD systems with drug loading ranging from 5 to 20% were prepared using PVP, PVP-VA, or HPMC-AS as the polymer matrix. The amorphization and homogeneity were confirmed by differential scanning calorimetry and powder X-ray diffraction. The intrinsic dissolution behavior of these ASDs was studied in 0.05 M HCl and phosphate-buffered saline (PBS) (pH 6.5). In 0.05 M HCl, PVP-VA ASDs with low drug loading (<15%) showed rapid dissolution accompanied with nano-species generation, while in the PVP system, rapid dissolution and nano-species generation were observed only when drug loading was less than 10%, and HPMC-AS ASDs always released slowly with no nano-species formation. In PBS, PVP-VA ASDs with drug loading less than 10% showed rapid dissolution accompanied with nano-species generation, while for PVP ASDs, rapid dissolution and nano-species generation were observed only when drug loading was 5%. However, 20% drug loading HPMC-AS ASDs exhibited rapid dissolution of felodipine and nano-species generation. When the drug loading was above the transition point of PVP-VA ASDs and PVP ASDs, the release rate was significantly lowered, and no nano-species was generated. To understand this phenomenon, drug-polymer interactions were studied using the m.p. depression method and the Flory-Huggins model fitting. The Flory-Huggins interaction parameters (χ) for felodipine/HPMC-AS, felodipine/PVP, and felodipine/PVP-VA were determined to be 0.62 ± 0.07, -0.55 ± 0.20, and -1.02 ± 0.21, resp., indicating the existence of the strongest attractive mol. interaction between felodipine and PVP-VA, followed by felodipine/PVP, but not in felodipine/HPMC-AS. Furthermore, dynamic vapor sorption further revealed that the mol. interactions between felodipine and PVP or PVP-VA were resistant to water. We concluded that water-resistant drug-polymer interactions in felodipine/polymer systems were responsible for the formation of nano-species, which further facilitated the rapid initial drug dissolution Molecular Pharmaceutics published new progress about amorphous solid dispersion; drug−polymer interaction; intrinsic dissolution; nano-species; water resistant. 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

Sakamoto, Aoi published the artcileDissolution Kinetics of Nifedipine-Ionizable Polymer Amorphous Solid Dispersion: Comparison Between Bicarbonate and Phosphate Buffers, Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is amorphous solid dispersion; bicarbonate; dissolution test; floating lid; phosphate; supersaturation.

Abstract: Purpose: The intestinal fluid pH is maintained by the bicarbonate buffer system that shows unique properties regarding drug dissolution Nevertheless, current compendial dissolution tests use phosphate buffers. The purpose of the present study was to investigate the effect of bicarbonate and phosphate buffers on the dissolution profiles of amorphous solid dispersions (ASD) composed of ionizable polymers. Methods: Hydroxypropylmethylcellulose acetate succinate (HPMCAS), amino methacrylate copolymer (AMC), and hydroxypropylmethylcellulose (HPMC) were employed as acidic, basic, and neutral polymers, resp. Nifedipine (NIF) was used as a model drug. Dissolution profiles were measured in pH 6.5 bicarbonate and phosphate buffers by a mini-scale paddle dissolution test. The pH of bicarbonate buffers was maintained by the floating lid method. Results: The pH change of the bicarbonate buffer was suppressed to less than + 0.25 pH for 3 h by the floating lid method. In all cases, the NIF concentration was supersaturated against the solubility of crystalline NIF. The dissolution rates of HPMCAS and AMC ASDs were 1.5 to 2.0-fold slower in the bicarbonate buffer than in the phosphate buffer when compared at the same buffer capacity. The dissolution profile of HPMC ASD was not affected by the buffer species. The higher the buffer capacity and ionic strength, the faster the dissolution rate of HPMCAS ASD. Conclusion: The dissolution rate of ASDs with ionizable polymers would be overestimated by using unphysiol. phosphate buffer solutions It is important to use a biorelevant bicarbonate buffer solution for dissolution testing.

Pharmaceutical Research published new progress about amorphous solid dispersion; bicarbonate; dissolution test; floating lid; phosphate; supersaturation. 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

Lee, Hao-Wei published the artcileComparative efficacy of generic nifedipine versus brand-name amlodipine for hypertension management in Taiwan, Safety of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is amlodipine; generic; hypertension; nifedipine; outcome.

The control rate of hypertension remains concerning, indicating the requirement for better management strategies. The calcium channel blockers brand-name amlodipine and nifedipine with extended-release formulations demonstrate similar clin. efficacy. However, the efficacy of generic nifedipine remains obscure. We compared the efficacy of generic nifedipine and brand-name amlodipine in terms of cardiovascular (CV) outcomes. Patients prescribed generic nifedipine (SRFC CYH) or brand-name amlodipine besylate (Norvasc, Pfizer) between August 1, 2017, and July 31, 2018, were enrolled; patients with CV events within 3 mo were excluded. CV outcomes included CV death, nonfatal myocardial infarction (MI), nonfatal ischemic stroke, hospitalization for heart failure, and composite endpoints of 3P- and 4P-major adverse cardiac events (MACE). A total of 1625 patients treated with nifedipine (SRFC CYH) and 16 587 patients treated with Norvasc were included. After propensity score matching, there were 995 and 4975 patients in the nifedipine CYH and Norvasc groups, resp. At a mean follow-up period of 30.3 ± 6.4 mo, nifedipine CYH was comparable to Norvasc in terms of CV death (P = .107), nonfatal MI (P = .121), nonfatal ischemic stroke (P = .453), hospitalization for heart failure (P = .330), 3P-MACE (P = .584), and 4P-MACE (P = .274). Cox regression anal. revealed that nifedipine CYH and Norvasc had similar efficacy in terms of 3P-MACE (hazard ratio, 0.970; 95% confidence interval, 0.601-1.565, P = .900) and 4P-MACE (hazard ratio, 0.880; 95% confidence interval, 0.628-1.233, P = .459). In conclusion, Nifedipine SRFC CYH and Norvasc have comparable clin. efficacy for hypertension management.

Journal of Clinical Hypertension (Hoboken, NJ, United States) published new progress about amlodipine; generic; hypertension; nifedipine; outcome. 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, Safety of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Eroglu, Talip E published the artcileDifferential effects on out-of-hospital cardiac arrest of dihydropyridines: real-world data from population-based cohorts across two European countries., SDS of cas: 21829-25-4, the main research area is Amlodipine; Epidemiology; Nifedipine; Sudden cardiac arrest.

AIMS: Various drugs increase the risk of out-of-hospital cardiac arrest (OHCA) in the general population by impacting cardiac ion channels, thereby causing ventricular tachycardia/fibrillation (VT/VF). Dihydropyridines block L-type calcium channels, but their association with OHCA risk is unknown. We aimed to study whether nifedipine and/or amlodipine, often-used dihydropyridines, are associated with increased OHCA risk, and how these drugs impact on cardiac electrophysiology. METHODS AND RESULTS: We conducted a case-control study with VT/VF-documented OHCA cases with presumed cardiac cause from ongoing population-based OHCA registries in the Netherlands and Denmark, and age/sex/index date-matched non-OHCA controls (Netherlands: PHARMO Database Network, Denmark: Danish Civil Registration System). We included 2503 OHCA cases, 10 543 non-OHCA controls in Netherlands, and 8101 OHCA cases, 40 505 non-OHCA controls in Denmark. To examine drug effects on cardiac electrophysiology, we performed single-cell patch-clamp studies in human-induced pluripotent stem cell-derived cardiomyocytes. Use of high-dose nifedipine (â‰?0 mg/day), but not low-dose nifedipine (<60 mg/day) or amlodipine (any-dose), was associated with higher OHCA risk than non-use of dihydropyridines [Netherlands: adjusted odds ratios (ORadj) 1.45 (95% confidence interval 1.02-2.07), Denmark: 1.96 (1.18-3.25)] or use of amlodipine [Netherlands: 2.31 (1.54-3.47), Denmark: 2.20 (1.32-3.67)]. Out-of-hospital cardiac arrest risk of (high-dose) nifedipine use was not further increased in patients using nitrates, or with a history of ischaemic heart disease. Nifedipine and amlodipine blocked L-type calcium channels at similar concentrations, but, at clinically used concentrations, nifedipine caused more L-type calcium current block, resulting in more action potential shortening. CONCLUSION: High-dose nifedipine, but not low-dose nifedipine or any-dose amlodipine, is associated with increased OHCA risk in the general population. Careful titration of nifedipine dose should be considered. European heart journal. Cardiovascular pharmacotherapy published new progress about Amlodipine; Epidemiology; Nifedipine; Sudden cardiac arrest. 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

Aali, Ehsan published the artcileCardioprotective Effects of Mebudipine in a Rat Model of Doxorubicin-Induced Heart Failure., Name: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is Amlodipine ; Doxorubicin; Endothelin-1 ; Heart failure ; Mebudipine.

Background: Mebudipine, a dihydropyridine calcium-channel blocker (CCB), shows greater time- and voltage-dependent inhibitory effects than nifedipine. Its significant negative chronotropic effects without having considerable negative inotropic properties may make it a suitable candidate for the pharmacotherapy of heart failure (HF). This study aimed to investigate the possible beneficial action of mebudipine in a rat model of HF. Methods: The present study carried out in the Department of Pharmacology at the Iran University of Medical Sciences during the years of 2009-2011. An experimental model of HF was induced in male Wistar rats using doxorubicin (DOX). The rats were divided into five groups with seven animals in each group: normal control group, DOX-induced HF control groups, and treatment groups. The animals were administered DOX for 15 days. A consistent deterioration occurred after a four-week rest period. The animals were then treated with intraperitoneal mebudipine (0.5 mg/kg) and intraperitoneal amlodipine (0.35 mg/kg), as well as an equal volume of distilled water for 15 days. The plasma levels of big endothelin-1 (BET-1), creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), as well as the clinical status (heart rate and blood pressure), were assessed before and after treatment. Statistical analysis was performed with SPSS software using parametric and nonparametric ANOVA. Results: Mebudipine and amlodipine reversed the increased plasma BET-1 values in the treated animals when compared with the HF control group (0.103 and 0.112 vs 0.231 pg/mL, respectively). The increased plasma levels of AST, ALT, CK-MB, and LDH were also reversed in the HF animals that received mebudipine or amlodipine. Conclusion: The administration of mebudipine to HF animals, akin to amlodipine, palliated the clinical and biochemical signs of the disease in the present study. The abstract was presented in the Iranian Congress of Physiology and Pharmacology as a poster and published in the Scientific Information Database as a supplement (2015; Vol 22).

Iranian journal of medical sciences published new progress about Amlodipine ; Doxorubicin; Endothelin-1 ; Heart failure ; Mebudipine. 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

Gudmundsson, Kristjan S. published the artcileAn improved large-scale synthesis of 2-amino-4-chloropyridine and its use for the convenient preparation of various polychlorinated 2-aminopyridines, Recommanded Product: Methyl 4-chloropicolinate, the main research area is aminochloropyridine preparation chlorination; polychlorinated aminopyridine preparation; pyridine amino polychlorinated preparation.

An efficient large scale synthesis of 2-amino-4-chloropyridine (I) has been achieved through a modification of existing literature procedures. I was used to prepare the previously unreported 2-amino-4,5-dichloropyridine. The known 2-amino-3,4-dichloropyridine and 2-amino-3,4,5-trichloropyridine were prepared from I by new routes and in higher yields than previously reported.

Synthetic Communications published new progress about aminochloropyridine preparation chlorination; polychlorinated aminopyridine preparation; pyridine amino polychlorinated preparation. 24484-93-3 belongs to class pyridine-derivatives, name is Methyl 4-chloropicolinate, and the molecular formula is C7H6ClNO2, Recommanded Product: Methyl 4-chloropicolinate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

de Heus, Rianne A. A. published the artcileBlood Pressure Variability and Progression of Clinical Alzheimer Disease, Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is Alzheimer disease; activities of daily living; blood pressure; cognition; hypertension.

Blood pressure variability (BPV) has been shown to have predictive value over blood pressure (BP) levels alone in stroke patients. We assessed whether BPV predicts cognitive and functional decline in Alzheimer disease, using data from a randomized trial (NILVAD [A European Multicentre Double-blind Placebo-controlled Phase III Trial of Nilvadipine in Mild to Moderate Alzheimer′s Disease]). Patients with mild-to-moderate Alzheimer disease were included if they had â‰? office BP measurements available to determine visit-to-visit BPV. Day-to-day BPV was assessed using home BP measurements in a subsample. The variation independent of mean was used to calculate BPV. Outcomes were change in Alzheimer′s Disease Assessment Scale-cognitive subscale-12 and Disability Assessment for Dementia after 1 and 1.5 years. A total of 460 patients aged 72.1 (SD=8.1) years, with mean BP of 134.0/75.1 (10.9/6.3) mm Hg were included. After 1 yr, patients in the highest quartile of BPV had deteriorated more on Alzheimer′s Disease Assessment Scale-cognitive subscale compared with patients in the lowest quartile (systolic: β, 2.24 [95% CI, 0.11-4.38], P=0.040; diastolic: β, 2.54 [95% CI, 0.33-4.75] P=0.024). This association was still present after 1.5 years (systolic: β, 2.86 [95% CI, 0.35-5.36], P=0.026; diastolic: β, 3.30 [95% CI, 0.67-5.93], P=0.014). There was no effect of visit-to-visit BPV on Disability Assessment for Dementia. Day-to-day BPV was available for 46 patients. Significant associations were observed between day-to-day BPV and deterioration on Alzheimer′s Disease Assessment Scale-cognitive subscale (systolic: P=0.036) and Disability Assessment for Dementia (systolic: P=0.020; diastolic: P=0.007) after 1 yr, but not after 1.5 years. All associations were adjusted for potential confounders, including intervention group. In conclusion, this post hoc anal. indicates that higher visit-to-visit and day-to-day BPV might be associated with progression of Alzheimer disease. Targeting BPV may be a future target to slow decline in patients with Alzheimer disease. Clin. trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02017340.

Hypertension published new progress about Alzheimer disease; activities of daily living; blood pressure; cognition; hypertension. 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

Chretien, Marc L published the artcileSeverity of coeliac disease and clinical management study when using a CYP3A4 metabolised medication: a phase I pharmacokinetic study., Related Products of pyridine-derivatives, the main research area is adverse events; clinical pharmacology; coeliac disease; gastroenterology.

OBJECTIVE: Severity of coeliac disease depends in part on the extent of small intestinal mucosa injury. Patients with the most abnormal pathology have loss of duodenal villi CYP3A4, a drug-metabolising enzyme that inactivates many drugs. These patients are hypothesised to have greater systemic concentrations of felodipine, a drug which normally has low oral bioavailability secondary to intestinal CYP3A4-mediated metabolism. It serves as a representative for a class containing many medications. DESIGN: A phase I, open-label, single-dose, pharmacokinetic study. SETTING: London, Ontario, Canada. PARTICIPANTS: Patients with coeliac disease (n=47) with positive serology and healthy individuals (n=68). MAIN OUTCOME MEASURES: Patients with coeliac disease-upper gastrointestinal endoscopy and oral felodipine pharmacokinetics study within a 3-week period. Healthy individuals-oral felodipine pharmacokinetics study with water and grapefruit juice. RESULTS: Coeliac stratification categories: Group A (n=15, normal), B+C (n=16, intraepithelial lymphocytosis with/without mild villous blunting) and D (n=16, moderate/severe villous blunting). Groups A, B+C and D had linear trends of increasing felodipine AUC0-8; mean±SEM, 14.4±2.1, 17.6±2.8, 25.7±5.0; p<0.05) and Cmax (3.5±0.5, 4.0±0.6, 6.4±1.1; p<0.02), respectively. Healthy subjects receiving water had lower felodipine AUC0-8 (11.9±0.9 vs 26.9±0.9, p=0.0001) and Cmax (2.9±0.2 vs 7.7±0.2, p=0.0001) relative to those receiving grapefruit juice. CONCLUSIONS: Increased felodipine concentrations in patients with coeliac disease were most probably secondary to decreased small intestinal CYP3A4 expression. Patients with severe coeliac disease and healthy individuals with grapefruit juice had equivalently enhanced effect. Thus, patients with severe coeliac disease would probably experience similarly altered drug response, including overdose toxicity, from many important medications known to be metabolised by CYP3A4. Patients with coeliac disease with severe disease should be considered for other clinical drug management, particularly when there is the potential for serious drug toxicity. BMJ open published new progress about adverse events; clinical pharmacology; coeliac disease; gastroenterology. 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, Related Products of pyridine-derivatives.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

De Roos, K. B. published the artcileDeazapurine derivatives. V. New synthesis of 1- and 3-deaza-adenine and related compounds, Product Details of C7H6ClNO2, the main research area is adenines deaza; deazaadenines; imidazopyridines; pyridines imidazo; purines deaza.

Reinvestigation of the cyclization of 2,3,4-triaminopyridine by several procedures showed that both 7-aminoimidazo[4,5-b]pyridine (1-deaza-adenine) (I) and 4-aminoimidazo[4,5-c]pyridine (3-deazaadenine) (II) were always obtained. A new and convenient route to the synthesis of I was devised. An unambiguous synthesis of II is given. Ring closure of 2,4,5-triaminopyridine afforded 6-aminoimidazo[4,5-c]pyridine (3-deazaisoadenine).

Recueil des Travaux Chimiques des Pays-Bas published new progress about adenines deaza; deazaadenines; imidazopyridines; pyridines imidazo; purines deaza. 24484-93-3 belongs to class pyridine-derivatives, name is Methyl 4-chloropicolinate, and the molecular formula is C7H6ClNO2, Product Details of C7H6ClNO2.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Gefen, David published the artcileA case study of applying text analysis to identify possible adverse drug interactions: The case of Adalat (Nifedipine)., Recommanded Product: Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is Adalat; Nifedipine; congestive heart failure; medical records; text analysis.

Adalat (Nifedipine) is a calcium-channel blocker that is also used as an antihypertensive drug. The drug was approved by the US Food and Drug Administration in 1985 but was discontinued in 1996 on account, among other things, of interactions with other medications. Nonetheless, Adalat is still used in other countries to treat congestive heart failure. We examine all the congestive heart failure electronic health records of the largest medical center in Israel to discover whether, possibly, taking Adalat with other medications is associated with patient death. This study examines a semantic space built by running latent semantic analysis on the entire corpus of congestive heart failure electronic health records of that medical center, encompassing 8 years of data on almost 12,000 patients. Through this semantic space, the most highly correlated medications and medical conditions that co-occurred with Adalat were identified. This was done separately for men and women. The results show that Adalat is correlated with different medications and conditions across genders. The data also suggest that taking Adalat with Captopril (angiotensin-converting enzyme inhibitor) or Rulid (antibiotic) might be dangerous in both genders. The study thus demonstrates the potential of applying latent semantic analysis to identify potentially dangerous drug interactions that may have otherwise gone under the radar.

Health informatics journal published new progress about Adalat; Nifedipine; congestive heart failure; medical records; text analysis. 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