Tag: M.W=150-200

Cumming, Jared N. published the artcileStructure based design of iminohydantoin BACE1 inhibitors: Identification of an orally available, centrally active BACE1 inhibitor, Quality Control of 917471-30-8, the main research area is iminohydantoin imidazolidinone propynylpyridinylphenyl preparation BACE1 inhibitor Alzheimers.

From an initial lead 2-imino-1-methyl-4,4-diphenyl-5-imidazolidinone, a structure-based design approach led to identification of the novel, high-affinity iminohydantoin BACE1 inhibitor I that lowers CNS-derived Aβ following oral administration to rats. SAR development in the S3 and F’ subsites of BACE1 for this series, the synthetic approaches employed in this effort, and in vivo data for I are reported.

Bioorganic & 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, Quality Control of 917471-30-8.

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

Jin, Bo published the artcileSynthesis and biological evaluation of 3-(pyridine-3-yl)-2-oxazolidinone derivatives as antibacterial agents, Synthetic Route of 1079179-12-6, the main research area is pyridinyl oxazolidinone preparation mol docking antibiofilm antibacterial activity; 3-(pyridine-3-yl)-2-oxazolidinone; antibacterial activity; biofilm formation inhibitory activity; drug resistance development; molecular docking.

In this research, a series of 3-(pyridine-3-yl)-2-oxazolidinone derivatives I [R = (pyridin-3-yl)carbonyl, Me, N-cyclohexylcarbamoyl, etc.], II (X = F, H) was designed, synthesized, and evaluated for in vitro antibacterial activity, which included bacteriostatic, morphol., kinetic studies, and mol. docking. The results demonstrated that compounds II [R = cyclohexanecarbonyl, (2E)-3-(furan-2-yl)prop-2-enoyl (III), (2E)-3-(pyridin-3-yl)prop-2-enoyl, N-(4-chlorophenyl)carbamoyl; X = F] exhibited strong antibacterial activity similar to that of linezolid toward five Gram-pos. bacteria. After observing the effect of the drug on the morphol. and growth dynamics of the bacteria, the possible modes of action were predicted by mol. docking. Furthermore, the antibiofilm activity and the potential drug resistance assay were proceeded. These compounds exhibited universal antibiofilm activity and compound III showed significant concentration-dependent inhibition of biofilm formation. Compound III also showed a stable effect on S. pneumoniae (ATCC 49619) with less drug resistance growth for 15 days, which is much longer than that of linezolid. Overall, these results can be used to guide further exploration of novel antimicrobial agents.

Frontiers in Chemistry (Lausanne, Switzerland) published new progress about Antibacterial agents. 1079179-12-6 belongs to class pyridine-derivatives, name is 2-Chloro-3-fluoro-5-nitropyridine, and the molecular formula is C5H2ClFN2O2, Synthetic Route of 1079179-12-6.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Fontaine, Fanny published the artcileFirst identification of boronic species as novel potential inhibitors of the Staphylococcus aureus NorA efflux pump, COA of Formula: C6H8BNO2S, the main research area is boron compound transport protein NorA Staphylococcus.

Overexpression of efflux pumps is an important mechanism of bacterial resistance that results in the extrusion of antimicrobial agents outside the bacterial cell. Inhibition of such pumps appears to be a promising strategy that could restore the potency of existing antibiotics. The NorA efflux pump of Staphylococcus aureus confers resistance to a wide range of unrelated substrates, such as hydrophilic fluoroquinolones, leading to a multidrug-resistance phenotype. Here, 150 heterocyclic boronic species were evaluated for their activity against susceptible and resistant strains of S. aureus. Twenty-four hit compounds, although inactive when tested alone, were found to potentiate ciprofloxacin activity by a 4-fold increase at concentrations ranging from 0.5 to 8 μg/mL against S. aureus 1199B, which overexpresses NorA. Boron-free analogs showed no biol. activity, thus revealing that the boron atom is crucial for biol. activity. This work describes the first reported efflux pump inhibitory activity of boronic acid derivatives

Journal of Medicinal Chemistry published new progress about Antibacterial agents. 321438-86-2 belongs to class pyridine-derivatives, name is 6-(Methylthio)pyridin-3-ylboronic acid, and the molecular formula is C6H8BNO2S, COA of Formula: C6H8BNO2S.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Yang, Yu-Ming published the artcileSilver-Mediated Trifluoromethoxylation of (Hetero)aryldiazonium Tetrafluoroborates, Name: 2-Chloro-3-(trifluoromethoxy)pyridine, the main research area is silver mediated Sandmeyer fluoromethoxylation aryl heteroaryl amine.

Here we report a silver-mediated trifluoromethoxylation of (hetero)aryldiazonium tetrafluoroborates by converting an aromatic amino group into an OCF3 group. This method, which can be considered to be a trifluoromethoxylation variation of the classic Sandmeyer-type reaction, uses readily available aryl and heteroaromatic amines as starting materials and AgOCF3 as trifluoromethoxylating reagents. The broad substrate scope and simple, mild reaction condition made this transformation a valuable method in constructing aryl-OCF3 bonds.

Organic Letters published new progress about Aromatic amines Role: RCT (Reactant), RACT (Reactant or Reagent). 1206980-39-3 belongs to class pyridine-derivatives, name is 2-Chloro-3-(trifluoromethoxy)pyridine, and the molecular formula is C6H3ClF3NO, Name: 2-Chloro-3-(trifluoromethoxy)pyridine.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Riflade, Benoit published the artcilePd-Containing Organopolyoxometalates Derived from Dawson Polyoxometalate [P2W15V3O62]9-: Lewis Acidity and Dual Site Catalysis, Recommanded Product: Ethyl 6-chloropicolinate, the main research area is palladium containing organopolyoxometalate derived Dawson polyoxometalate; Lewis acidity dual site catalysis; allylation sulfonylimine aldehyde.

Grafting of a palladium complex to the Dawson vanadotungstate polyanion [P2W15V3O62]9- via an organic ligand generates a large family of pincer-type hybrid polyoxometalates. The palladium-POM derivatives have dual catalytic properties. Unlike their parent inorganic polyanions, they catalyze allylations while retaining their oxidant character, which leads to single-pot dual site catalysis. This opens a new route for multicatalytic reactions.

Organic Letters published new progress about Acid chlorides Role: RCT (Reactant), RACT (Reactant or Reagent). 21190-89-6 belongs to class pyridine-derivatives, name is Ethyl 6-chloropicolinate, and the molecular formula is C8H8ClNO2, Recommanded Product: Ethyl 6-chloropicolinate.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

Yang, Chu-Ting published the artcilePd-Catalyzed Vinylation of Aryl Halides with Inexpensive Organosilicon Reagents Under Mild Conditions, Application In Synthesis of 21190-89-6, the main research area is aryl chloride bromide organosilicon reagent vinylation palladium catalyst; Am/Cm separation; cross-coupling; palladium; silicon; substituent effects.

Pd-catalyzed Hiyama vinylation reaction of non-activated aryl chlorides and bromides under mild conditions was developed. The use of efficient vinyl donors and electron-rich sterically hindered phosphine ligands was critical for the success of the reaction. The products of this transformation can be used for Am/Cm separation, an important challenge in nuclear fuel reprocessing. The substituent effect on Am/Cm separating selectivity was also achieved, which could contribute to the development of new chromatog. materials for the separation of Am and Cm.

Chemistry – A European Journal published new progress about Aryl bromides Role: RCT (Reactant), RACT (Reactant or Reagent). 21190-89-6 belongs to class pyridine-derivatives, name is Ethyl 6-chloropicolinate, and the molecular formula is C8H8ClNO2, Application In Synthesis of 21190-89-6.

Referemce:
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem