Category: pyridine-derivatives

Demirdag, Hatice Gamze published the artcileEvaluation of relationship between antihypertensive drug usage and dermatoscopic features in patients with keratinizing skin cancer, SDS of cas: 21829-25-4, the main research area is hydrochlorothiazide antihypertensive diagnosis keratinizing skin cancer; actinic keratosis; antihypertensive drug; cSCC; dermatoscopy; dermoscopy; intraepidermal carcinoma; keratoacanthoma; squamous cell carcinoma.

Keratinizing skin cancers including actinic keratoses (AK), in situ squamous cell carcinoma/Bowens disease/intraepidermal carcinoma (IEC), invasive cutaneous squamous cell carcinoma (cSCC) and keratoacanthoma share similar dermatoscopic features and also reveal different patterns that assist in their diagnosis. Recently epidemiol. studies reveal the association between antihypertensive drugs and skin cancer risk, especially cSCC. This study aims to determine the dermatoscopic features of keratinizing skin cancer in patients using antihypertensive drug and compare with non-users. A total of 46 patients with 64 keratinizing skin cancer lesions were included in the study. The demog., clin. characteristic of patients, the number, duration, localization and dermatoscopic features from each lesion were collected. First, we evaluated the dermatoscopic features according to the histopathol. diagnosis. Then, all patients were divided into two groups as users of antihypertensive drugs and non-users. The dermatoscopic features were compared in terms of antihypertensive drug usage and histopathol. diagnosis in antihypertensive drug users and non-users, sep. The users of anti-hypertensive drugs were 22 (47,8%) and non-users 24 (52,2%). Of the total 64 lesions including 47 AK, 5 IEC, 10 cSCC, and 2 keratoacanthoma were evaluated. White structureless area was found statistically significant in cSCC lesions of patients using antihypertensive drugs (P = .004). This finding in cSCC may be a clue for antihypertensive drug usage and these drugs may be a predisposan factor for dermal fibrosis. Regardless of histopathol., dermatoscopic features show no statistically difference between antihypertensive drug users and non-users (P > .05). Clearer results can be obtained by conducting more detailed and long-term studies.

Dermatologic Therapy published new progress about Actinic keratosis. 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

Hamed, Ezzat A. published the artcileNucleophilic substitutions at the pyridine ring: kinetics of the reaction of 2-chloro-3-nitro and 2-chloro-5-nitropyridines with piperidine and morpholine in methanol and benzene, Formula: C9H11N3O3, the main research area is nucleophilic substitution chloronitropyridine kinetics mechanism.

The kinetics of the reactions of 2-chloro-3-nitropyridine (ortho-like) and 5-nitro (para-like) isomer with morpholine and piperidine were studied in methanol and benzene at several amine concentrations and at 25-45°. The data show that k3-NO 2/k5-NO2 ratios are less than unity in methanol. The steric hindrance in the transition state of the 3-nitro (ortho-like) isomer retards o-substitution while the stability of p-quinonoid structure of the 5-nitro (para-like) isomer favors p-substitution. In benzene, the k3-NO2/k5-NO2 ratios are greater than unity. The hydrogen bonding formation between the ammonium hydrogen and the ortho-nitro group in the transition state of 3-nitro isomer favors the o-substitution.

International Journal of Chemical Kinetics published new progress about Activation energy. 26820-62-2 belongs to class pyridine-derivatives, name is 4-(5-Nitropyridin-2-yl)morpholine, and the molecular formula is C9H11N3O3, Formula: C9H11N3O3.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Ali, K. A. published the artcileThe thermal analysis of felodipine and ramipril: application to quality control, Quality Control of 72509-76-3, the main research area is Triacor felodipine ramipril quality control thermogravimetry.

Thermal behavior of Felodipine (FEL) and Ramipril (RAM) drugs was studied in drug substance, binary mixture and co-formulated tablets. Some thermal anal. methods such as thermogravimetric anal. (TGA), derivative thermogravimetry (DrTGA), DTA (DTA) and differential scanning calorimetry (DSC) were used to investigate the thermal behavior of both drugs. The thermogravimetric data allowed the determination of different thermodn. and kinetic parameters such as: Ea, ΔH, ΔS and ΔG. The drugs purity was found to be 99.88% and 99.92% for FEL and RAM, resp. The simplicity, speed and low cost of the thermal anal. justify its application in the quality control of pharmaceutical drugs.

Analytical Chemistry: An Indian Journal published new progress about Activation energy. 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

Perkins, Emma M. published the artcileAltered network properties in C9ORF72 repeat expansion cortical neurons are due to synaptic dysfunction, Synthetic Route of 21829-25-4, the main research area is human cortical neuron synaptic dysfunction CORF network property; ALS; C9ORF72; Cortical; Electrophysiology; FTD; Hyperexcitability; Network; Neuron; Repeat expansion; Synaptic.

Physiol. disturbances in cortical network excitability and plasticity are established and widespread in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) patients, including those harbouring the C9ORF72 repeat expansion (C9ORF72RE) mutation – the most common genetic impairment causal to ALS and FTD. Noting that perturbations in cortical function are evidenced pre-symptomatically, and that the cortex is associated with widespread pathol., cortical dysfunction is thought to be an early driver of neurodegenerative disease progression. However, our understanding of how altered network function manifests at the cellular and mol. level is not clear. To address this we have generated cortical neurons from patient-derived iPSCs harbouring C9ORF72RE mutations, as well as from their isogenic expansion-corrected controls. We have established a model of network activity in these neurons using multi-electrode array electrophysiol. We have then mechanistically examined the physiol. processes underpinning network dysfunction using a combination of patch-clamp electrophysiol., immunocytochem., pharmacol. and transcriptomic profiling. We find that C9ORF72RE causes elevated network burst activity, associated with enhanced synaptic input, yet lower burst duration, attributable to impaired pre-synaptic vesicle dynamics. We also show that the C9ORF72RE is associated with impaired synaptic plasticity. Moreover, RNA-seq anal. revealed dysregulated mol. pathways impacting on synaptic function. All mol., cellular and network deficits are rescued by CRISPR/Cas9 correction of C9ORF72RE. Our study provides a mechanistic view of the early dysregulated processes that underpin cortical network dysfunction in ALS-FTD. These findings suggest synaptic pathophysiol. is widespread in ALS-FTD and has an early and fundamental role in driving altered network function that is thought to contribute to neurodegenerative processes in these patients. The overall importance is the identification of previously unidentified defects in pre and postsynaptic compartments affecting synaptic plasticity, synaptic vesicle stores, and network propagation, which directly impact upon cortical function.

Molecular Neurodegeneration published new progress about Alzheimer disease. 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

Scott, Jack D. published the artcileDiscovery of the 3-Imino-1,2,4-thiadiazinane 1,1-Dioxide Derivative Verubecestat (MK-8931)-A β-Site Amyloid Precursor Protein Cleaving Enzyme 1 Inhibitor for the Treatment of Alzheimer’s Disease, Formula: C8H8BNO2, the main research area is verubecestat preparation BACE1 inhibitor structure activity Alzheimer disease.

Verubecestat (MK-8931), a diaryl amide substituted 3-imino-1,2,4-thiadiazinane 1,1-dioxide derivative, is a high-affinity β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor currently undergoing Phase 3 clin. evaluation for the treatment of mild to moderate and prodromal Alzheimer’s disease. Although not selective over the closely related aspartyl protease BACE2, verubecesat has high selectivity for BACE1 over other key aspartyl proteases, notably cathepsin D, and profoundly lowers CSF and brain Aβ levels in rats and nonhuman primates, and CSF Aβ levels in humans. In this annotation, the authors describe the discovery of verubecesat, including design, validation, and selected SAR around the novel iminothiadiazinane dioxide core, as well as aspects of its preclin. and Phase 1 clin. characterization.

Journal of Medicinal Chemistry published new progress about Alzheimer disease. 917471-30-8 belongs to class pyridine-derivatives, name is (5-(Prop-1-yn-1-yl)pyridin-3-yl)boronic acid, and the molecular formula is C8H8BNO2, Formula: C8H8BNO2.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Gravenfors, Ylva published the artcileNew Aminoimidazoles as β-Secretase (BACE-1) Inhibitors Showing Amyloid-β (Aβ) Lowering in Brain, Application of (5-(Prop-1-yn-1-yl)pyridin-3-yl)boronic acid, the main research area is aminoimidazole BACE1 inhibitor preparation crystal structure SAR permeability hERG; amyloid beta reduction brain aminoimidazole BACE1 inhibitor.

Amino-2H-imidazoles are described as a new class of BACE-1 inhibitors for the treatment of Alzheimer’s disease. Synthetic methods, crystal structures, and structure-activity relationships for target activity, permeability, and hERG activity are reported and discussed. Compound (S)-1m (I) was one of the most promising compounds in this report, with high potency in the cellular assay and a good overall profile. When guinea pigs were treated with compound (S)-1m, a concentration and time dependent decrease in Aβ40 and Aβ42 levels in plasma, brain, and CSF was observed The maximum reduction of brain Aβ was 40-50%, 1.5 h after oral dosing (100 μmol/kg). The results presented highlight the potential of this new class of BACE-1 inhibitors with good target potency and with low effect on hERG, in combination with a fair CNS exposure in vivo.

Journal of Medicinal Chemistry published new progress about Alzheimer disease. 917471-30-8 belongs to class pyridine-derivatives, name is (5-(Prop-1-yn-1-yl)pyridin-3-yl)boronic acid, and the molecular formula is C8H8BNO2, Application of (5-(Prop-1-yn-1-yl)pyridin-3-yl)boronic acid.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Stamford, Andrew W. published the artcileDiscovery of an Orally Available, Brain Penetrant BACE1 Inhibitor That Affords Robust CNS Aβ Reduction, Safety of (5-(Prop-1-yn-1-yl)pyridin-3-yl)boronic acid, the main research area is preparation oral brain penetrant BACE1 amyloid inhibitor Alzheimer’s; Alzheimer’s disease; Aβ40; BACE1; X-ray crystallography; iminopyrimidinone; inhibitor.

Inhibition of BACE1 to prevent brain Aβ peptide formation is a potential disease-modifying approach to the treatment of Alzheimer’s disease. Despite over a decade of drug discovery efforts, the identification of brain-penetrant BACE1 inhibitors that substantially lower CNS Aβ levels following systemic administration remains challenging. In this report we describe structure-based optimization of a series of brain-penetrant BACE1 inhibitors derived from an iminopyrimidinone scaffold. Application of structure-based design in tandem with control of physicochem. properties culminated in the discovery of compound 16, which potently reduced cortex and CSF Aβ40 levels when administered orally to rats.

ACS Medicinal Chemistry Letters published new progress about Alzheimer disease. 917471-30-8 belongs to class pyridine-derivatives, name is (5-(Prop-1-yn-1-yl)pyridin-3-yl)boronic acid, and the molecular formula is C8H8BNO2, Safety of (5-(Prop-1-yn-1-yl)pyridin-3-yl)boronic acid.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Ciordia, Myriam published the artcileApplication of Free Energy Perturbation for the Design of BACE1 Inhibitors, Product Details of C8H8BNO2, the main research area is free energy perturbation calculation BACE1 inhibitor drug design Alzheimer.

Novel spiroaminodihydropyrroles probing for optimized interactions at the P3 pocket of β-secretase 1 (BACE1) were designed with the use of free energy perturbation (FEP) calculations The resulting mols. showed pIC50 potencies in enzymic BACE1 inhibition assays ranging from approx. 5 to 7. Good correlation was observed between the predicted activity from the FEP calculations and exptl. activity. Simulations run with a default 5 ns approach delivered a mean unsigned error (MUE) between prediction and experiment of 0.58 and 0.91 kcal/mol for retrospective and prospective applications, resp. With longer simulations of 10 and 20 ns, the MUE was in both cases 0.57 kcal/mol for the retrospective application, and 0.69 and 0.59 kcal/mol for the prospective application. Other considerations that impact the quality of the calculations are discussed. This work provides an example of the value of FEP as a computational tool for drug discovery.

Journal of Chemical Information and Modeling published new progress about Alzheimer disease. 917471-30-8 belongs to class pyridine-derivatives, name is (5-(Prop-1-yn-1-yl)pyridin-3-yl)boronic acid, and the molecular formula is C8H8BNO2, Product Details of C8H8BNO2.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Meere, Martin published the artcileModelling phase separation in amorphous solid dispersions, Synthetic Route of 72509-76-3, the main research area is amorphous solid dispersion phase separation; Amorphous solid dispersion; Drug diffusion; Mathematical model; Phase separation.

Much work has been devoted to analyzing thermodn. models for solid dispersions with a view to identifying regions in the phase diagram where amorphous phase separation or drug recrystallization can occur. However, detailed partial differential equation non-equilibrium models that track the evolution of solid dispersions in time and space are lacking. Hence theor. predictions for the timescale over which phase separation occurs in a solid dispersion are not available. In this paper, we address some of these deficiencies by (i) constructing a general multicomponent diffusion model for a dissolving solid dispersion; (ii) specializing the model to a binary drug/polymer system in storage; (iii) deriving an effective concentration dependent drug diffusion coefficient for the binary system, thereby obtaining a theor. prediction for the timescale over which phase separation occurs; (iv) calculating the phase diagram for the Felodipine/HPMCAS system; and (iv) presenting a detailed numerical investigation of the Felodipine/HPMCAS system assuming a Flory-Huggins activity coefficient The numerical simulations exhibit numerous interesting phenomena, such as the formation of polymer droplets and strings, Ostwald ripening/coarsening, phase inversion, and droplet-to-string transitions. A numerical simulation of the fabrication process for a solid dispersion in a hot melt extruder was also presented. Solid dispersions are products that contain mixtures of drug and other materials e.g. polymer. These are liable to sep.-out over time – a phenomenon known as phase separation This means that it is possible the product differs both compositionally and structurally between the time of manufacture and the time it is taken by the patient, leading to poor bioavailability and so ultimately the shelf-life of the product has to be reduced. Theor. predictions for the timescale over which phase separation occurs are not currently available. Also lacking are detailed partial differential equation non-equilibrium models that track the evolution of solid dispersions in time and space. This study addresses these issues, before presenting a detailed investigation of a particular drug-polymer system.

Acta Biomaterialia published new progress about Amorphous materials. 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

Sarpal, Kanika published the artcilePhase Behavior of Amorphous Solid Dispersions of Felodipine: Homogeneity and Drug-Polymer Interactions, HPLC of Formula: 72509-76-3, the main research area is polymer interaction felodipine formulation; amorphous solid dispersions; differential scanning calorimetry; felodipine; hydrogen bonding; phase behavior; solid-state nuclear magnetic resonance spectroscopy.

In the current investigation, the role of drug-polymer hydrogen bonding (H-bonding) with respect to the phase behavior of amorphous solid dispersions (ASDs) is studied in depth on a nanometer level. Melt-quenched dispersions of felodipine (FEL) with poly(vinylpyrrolidone), or PVP, poly(vinylpyrrolidone-co-vinylacetate), or PVP/VA, and poly(vinylacetate), or PVAc, were prepared at drug loadings of 50-90% weight/weight Modulated differential scanning calorimetry (MDSC) was used to detect microscopic homogeneity for each set of ASDs. A single composition dependent glass transition temperature (Tg) was observed over the entire composition range in MDSC data for each set of ASDs; however some samples within each set of ASDs showed a crystallization exotherm and corresponding melting endotherm in the first heating scan. Solid-state NMR spectroscopy (SSNMR) was further employed to understand phase homogeneity in these systems. The proton spin-lattice relaxation times in the laboratory and rotating frame (1H T1 and T1ρ) for the drug and individual polymer for each set of ASDs were measured to evaluate phase homogeneity. On the basis of proton relaxation measurements, it was revealed that FEL:PVP and FEL:PVP/VA ASDs exhibited better compositional homogeneity than FEL:PVAc ASDs. The strength and the extent of H-bonding were studied by using 13C SSNMR spectra. In addition, deconvolution of the carbonyl region of amorphous FEL revealed that 40% of amorphous FEL mols. were hydrogen bonded (H-bonded) through dimers and the remaining 60% were free/non H-bonded. The dimer fraction decreased as the polymer content increased for each set of ASDs, while the free fraction increased. This indicated that the polymers containing hydrogen bond acceptor groups disrupted dimers and formed intermol. H-bonding interactions with FEL. The strength and extent of FEL:polymer H-bonding was rank ordered as PVP > PVP/VA > PVAc. These findings were also confirmed through DFT calculations on these systems. Our results suggest that drug-polymer H-bonding interaction may impact the phase homogeneity in ASDs formulated by a specific method. The data from the current study further demonstrate that SSNMR is a powerful tool for characterizing phase homogeneity in ASDs with sub-50 nm resolution In addition, SSNMR can provide insights into drug-polymer interactions and speciation in ASDs.

Molecular Pharmaceutics published new progress about Amorphous materials. 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