Day: November 30, 2022

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

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

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

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

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

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

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

Kokova, Vesela Yu. published the artcileEtifoxine does not impair muscle tone and motor function in rats as assessed by in vivo and in vitro methods, Related Products of pyridine-derivatives, the main research area is Etifoxine impair muscle tone motor rats.

The purpose of our study is to evaluate the effects of the translocator protein (TSPO) ligand etifoxine on muscle tone and locomotor activity. In addition, the mechanism of action of etifoxine on the presynaptic membrane and neuromuscular junction is investigated. These effects of etifoxine were examined employing the following methods: 1 in vivo experiments using bar holding test and activity cage test, and 2 comparative in vitro studies with nifedipine on indirectly-elicited twitches of striated abdominal muscle preparations Etifoxine in doses 50 mg/kg and 100 mg/kg i.p. does not produce any significant changes in locomotor activity and muscle tone of intact rats. Nifedipine (10-5 M) induces a significant decrease in the muscle force of striated muscle preparations Etifoxine (10-8-10-4 M) has no significant effect on indirectly-elicited twitch tension. Results show that the TSPO ligand etifoxine has no myorelaxant effect. The activation of TSPO is not associated with a reduction in muscle tone and motor impairment. Etifoxine does not affect the presynaptic membrane and its influence on L-type Ca2+-channels is insignificant. Etifoxine does not act as a competitive antagonist of acetylcholine and does not impair the impulse transmission in the neuromuscular junction.

General Physiology and Biophysics published new progress about Locomotor behavior. 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

Lu, Hsin-Che published the artcileAchieving Low-Energy Driven Viologens-Based Electrochromic Devices Utilizing Polymeric Ionic Liquids, Safety of 1,1-Di-n-octyl-4,4-bipyridinium Dibromide, the main research area is viologen electrochromic device polymer electrolyte ionic liquid; UV-curing; diffusion coefficient; electrochemistry; electrochromic devices (ECDs); gel electrolytes; ionic liquids; polymer electrolytes; viologens.

Three kinds of viologens-based electrochromic devices (ECDs) (heptyl viologen (HV(BF4)2), octyl viologen (OV(BF4)2), and nonyl viologen (NV(BF4)2)) were fabricated utilizing ferrocene (Fc) as a redox mediator. Among them, the NV(BF4)2-based ECD exhibits the highest coloration efficiency (36.2 cm2/C) owing to the lowest driving energy. Besides, switching between 0 and 1.2 V, the NV(BF4)2-based ECD shows a desirable initial transmittance change (ΔT = 56.7% at 605 nm), and long-term stability (ΔT = 45.4% after 4000 cycles). A UV-cured polymer electrolyte containing polymeric ionic liquid (PIL, 1-allyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide) and ethoxylated trimethylolpropane triacrylate (ETPTA) was introduced to the NV(BF4)2-based ECD. By controlling the weight percentage of the PIL, different curing degrees of the polymer electrolytes were obtained and led to an improved stability of the NV(BF4)2-based ECD because of the immobilization of NV(BF4)2. This observation was explained by calculating the apparent diffusivity (Dapp) of the redox species in the NV(BF4)2-based ECD under various curing degrees. Increasing the amount of PIL leads to a lower driven energy needed for the NV(BF4)2-based ECD, following the same trend as the value of Dapp. Among all NV(BF4)2-based ECDs, 20 weight % of PIL addition (20-PIL ECD) exhibits large transmittance change (ΔT = 55.2% at 605 nm), short switching times (2.13 s in coloring and 2.10 s in bleaching), high coloration efficiency (60.4 and 273.5 cm2/C at 605 nm, after excluding the c.d. at the steady state), and exceptional cycling stability (ΔT = 53.8% after 10,000 cycles, or retained 97.5% of its initial ΔT).

ACS Applied Materials & Interfaces published new progress about Cyclic voltammetry. 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, Safety of 1,1-Di-n-octyl-4,4-bipyridinium Dibromide.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Goren, Zafrir published the artcilePhotochemical and chemical reduction of vicinal dibromides via phase transfer of 4,4′-bipyridinium radical: the role of radical disproportionation, HPLC of Formula: 36437-30-6, the main research area is reductive debromination octylbispyridinium bromide; two phase debromination mechanism; aryldibromoethane debromination dithionite alkylviologen; photochem dehalogenaton halostilbene EDTA.

Reduction of 1,2-dibromo-1,2-diarylethanes is accomplished in a 2-phase system that includes dioctyl-4,4′-bipyridinium dibromide (C8V2+), and a reducing agent such as dithionite or glucose solubilized in the aqueous phase. The C8V2+ mediates the debromination reactions and is recycled in the process. The initially formed radical cation C8V+â€?is extracted from the aqueous phase into the organic layer, and undergoes disproportionation to the biradical C8V. The solubility properties of the disproportionation products shift the disproportionation equilibrium in the 2-phase system, towards in the biradical C8V, since C8V2+ is reextracted into the aqueous phase. The photochem. reduction of dihalostilbenes is also accomplished by substitution of the reducing agent in the aqueous phase with a sensitizer, Ru(bipy)32+, and EDTA as electron donor.

Journal of the American Chemical Society published new progress about Cyclic voltammetry. 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, HPLC of Formula: 36437-30-6.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem