Day: November 23, 2022

Durka, Krzysztof published the artcileSynthesis, characterization and photoluminescence of 8-oxyquinolinato organoboron complexes derived from pyrazole, Category: pyrazoles-derivatives, the publication is Tetrahedron Letters (2017), 58(12), 1185-1189, database is CAplus.

A 1-pot protocol was developed for the synthesis of luminescent heteroleptic diaryldiborinic complexes containing the central aryl ring bonded to two B atoms substituted with pyrazole and complexed with 8-hydroxyquinoline. The luminescent properties of these compounds were measured. In dilute solutions they exhibited an emission at �13 nm with quantum yields of 22-27% which are typical for borinic 8-hydroxyquinoline complexes. The only exception was the complex containing the bithiophene scaffold, for which no fluorescence was observed The obtained pyrazole-based complexes show improved solubility and thermal stability with respect to their Ph analogs. The exptl. UV-visible absorption and emission data are supported by theor. calculations of the frontier MOs, revealing the aromatic linker to quinolinato ligand excitation mechanism.

Tetrahedron Letters published new progress about 930-36-9. 930-36-9 belongs to pyrazoles-derivatives, auxiliary class Pyrazole, name is 1-Methylpyrazole, and the molecular formula is C4H6N2, Category: pyrazoles-derivatives.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Bonazzi, Simone published the artcileDiscovery of a Brain-Penetrant ATP-Competitive Inhibitor of the Mechanistic Target of Rapamycin (mTOR) for CNS Disorders, Quality Control of 763120-58-7, the publication is Journal of Medicinal Chemistry (2020), 63(3), 1068-1083, database is CAplus and MEDLINE.

Recent clin. evaluation of everolimus for seizure reduction in patients with tuberous sclerosis complex (TSC), a disease with overactivated mechanistic target of rapamycin (mTOR) signaling, has demonstrated the therapeutic value of mTOR inhibitors for central nervous system (CNS) indications. Given that everolimus is an incomplete inhibitor of the mTOR function, we sought to develop a new mTOR inhibitor that has improved properties and is suitable for CNS disorders. Starting from an inhouse purine-based compound, optimization of the physicochem. properties of a thiazolopyrimidine series led to the discovery of the small mol. 7, a potent and selective brain-penetrant ATP-competitive mTOR inhibitor. In neuronal cell-based models of mTOR hyperactivity, 7 corrected the mTOR pathway activity and the resulting neuronal overgrowth phenotype. The new mTOR inhibitor 7 showed good brain exposure and significantly improved the survival rate of mice with neuronal-specific ablation of the Tsc1 gene. These results demonstrate the potential utility of this tool compound to test therapeutic hypotheses that depend on mTOR hyperactivity in the CNS.

Journal of Medicinal Chemistry published new progress about 763120-58-7. 763120-58-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is 1H-Pyrazole-4-boronic acid, and the molecular formula is C3H5BN2O2, Quality Control of 763120-58-7.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Kearns, Hayleigh published the artcileSERS Detection of Multiple Antimicrobial-Resistant Pathogens Using Nanosensors, Synthetic Route of 19959-71-8, the publication is Analytical Chemistry (Washington, DC, United States) (2017), 89(23), 12666-12673, database is CAplus and MEDLINE.

Successful pathogen detection is crucial for public health as the threat of infectious disease is dramatically increasing globally due to bacteria developing resistance to many antimicrobial drugs. The increase in bacterial infections has led to urgent demands for simpler, faster, and more reliable detection methods to be developed allowing the most appropriate therapy to be provided. Surface enhanced Raman scattering (SERS) is an anal. technique which has gained a great deal of interest for biosensing due to its sensitivity, selectivity, and multiplexing capabilities. A new bionanosensor has been developed for the isolation and detection of multiple bacterial pathogens via magnetic separation and SERS. This novel assay format involves using lectin functionalized magnetic nanoparticles for capture and isolation of bacteria from the sample matrix followed by specifically detecting bacterial pathogens using SERS active nanoparticles functionalized with antibodies which are strain specific. Therefore, the sample is captured using a “magnetic plug” and interrogated with a laser allowing simple and fast optical detection. Three bacterial pathogens (Escherichia coli, Salmonella typhimurium, and methicillin-resistant Staphylococcus aureus) were successfully isolated and detected, with the lowest concentration for each of the strains detected at just 10¹ colony forming units per mL (CFU/mL). In addition to single pathogen detection, a mixture of all three bacterial strains was isolated and identified within the same sample matrix using SERS with the triplex detection also being confirmed using principal component anal. Herein, this multiplexed bionanosensor is capable of providing rapid and sensitive discrimination of bacterial pathogens both individually, and within a multiplex system, offering opportunities for future point of care devices and advancements in biomedical applications.

Analytical Chemistry (Washington, DC, United States) published new progress about 19959-71-8. 19959-71-8 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Pyridine, name is 4-(1H-Pyrazol-4-yl)pyridine, and the molecular formula is C8H7N3, Synthetic Route of 19959-71-8.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Kearns, Hayleigh published the artcileSERS Detection of Multiple Antimicrobial-Resistant Pathogens Using Nanosensors, Synthetic Route of 19959-71-8, the publication is Analytical Chemistry (Washington, DC, United States) (2017), 89(23), 12666-12673, database is CAplus and MEDLINE.

Successful pathogen detection is crucial for public health as the threat of infectious disease is dramatically increasing globally due to bacteria developing resistance to many antimicrobial drugs. The increase in bacterial infections has led to urgent demands for simpler, faster, and more reliable detection methods to be developed allowing the most appropriate therapy to be provided. Surface enhanced Raman scattering (SERS) is an anal. technique which has gained a great deal of interest for biosensing due to its sensitivity, selectivity, and multiplexing capabilities. A new bionanosensor has been developed for the isolation and detection of multiple bacterial pathogens via magnetic separation and SERS. This novel assay format involves using lectin functionalized magnetic nanoparticles for capture and isolation of bacteria from the sample matrix followed by specifically detecting bacterial pathogens using SERS active nanoparticles functionalized with antibodies which are strain specific. Therefore, the sample is captured using a “magnetic plug” and interrogated with a laser allowing simple and fast optical detection. Three bacterial pathogens (Escherichia coli, Salmonella typhimurium, and methicillin-resistant Staphylococcus aureus) were successfully isolated and detected, with the lowest concentration for each of the strains detected at just 10¹ colony forming units per mL (CFU/mL). In addition to single pathogen detection, a mixture of all three bacterial strains was isolated and identified within the same sample matrix using SERS with the triplex detection also being confirmed using principal component anal. Herein, this multiplexed bionanosensor is capable of providing rapid and sensitive discrimination of bacterial pathogens both individually, and within a multiplex system, offering opportunities for future point of care devices and advancements in biomedical applications.

Analytical Chemistry (Washington, DC, United States) published new progress about 19959-71-8. 19959-71-8 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Pyridine, name is 4-(1H-Pyrazol-4-yl)pyridine, and the molecular formula is C8H7N3, Synthetic Route of 19959-71-8.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Vernier, William F. published the artcileRegioselective palladium-catalyzed C-H arylation of 4-alkoxy and 4-thioalkyl pyrazoles, Computed Properties of 930-36-9, the publication is Tetrahedron Letters (2017), 58(49), 4587-4590, database is CAplus.

Alkoxy- and alkylthiopyrazoles such as 4-benzyloxy-1-methylpyrazole underwent regioselective arylation with aryl and heteroaryl bromides in the presence of Pd(OAc)₂ and either SPhos or QPhos in 1,4-dioxane at 70-90 °C to yield arylpyrazoles such as I and an arylimidazole in 19-88% yields; 1-methylpyrazole, 4-chloro-1-methylpyrazole, 1-phenyl-4-pyrazolecarboxaldehyde, and 1-methylimidazole also underwent arylation under similar conditions but required higher temperatures Bromoaralkyl pyrazolyl ethers and thioethers such as 4-(2-bromobenzyloxy)-1-methylpyrazole underwent intramol. arylation to yield fused pyrazoles such as pyrazoloisobenzopyran II in 34-93% yields.

Tetrahedron Letters published new progress about 930-36-9. 930-36-9 belongs to pyrazoles-derivatives, auxiliary class Pyrazole, name is 1-Methylpyrazole, and the molecular formula is C15H12O8, Computed Properties of 930-36-9.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Chen, Yantao published the artcileSynthesis of Enantiomerically Pure 2-Heteroaromatic-Substituted 1,2-Amino Alcohols from Chiral tert-Butanesulfinyl Aldimines, Name: 1-Methylpyrazole, the publication is Synthesis (2015), 47(5), 679-691, database is CAplus.

Nine R/S pairs of 2-heteroaromatic-substituted 1,2-amino alcs. were synthesized through 1,2-nucleophilic addition between chiral N-(tert-butylsulfinyl)imines and heteroaromatic carbanions. In most cases, the RS-isomer of N-(tert-butylsulfinyl)imines afforded the (R)-amino alc. from deprotection of the major diastereomer, and (S/S)-imines afforded the (S)-product. In general, this procedure allows for the preparation of a variety of enantiomeric pairs of 2-heteroaromatic-substituted 1,2-amino alcs. on a practical scale (>10 g) in two steps in good yields. Aldimines were prepared from [S(S)]-2-methyl-2-propanesulfinamide and [S(R)]-2-methyl-2-propanesulfinamide. The synthesis of the target compounds was achieved by a reaction of , [S(S)]-N-[2-[[(1,1-dimethylethyl)dimethylsilyl]oxy]ethylidene]-2-methyl-2-propanesulfinamide (chiral auxiliary, tert-butanesulfinyl aldimine) and [S(R)]-N-[2-[[(1,1-dimethylethyl)dimethylsilyl]oxy]ethylidene]-2-methyl-2-propanesulfinamide (chiral auxiliary) with 5-bromo-2-methoxypyridine, 3-bromo-1-methyl-1H-pyrazole, 1-methyl-1H-imidazole, 2-chloro-1-methyl-1H-imidazole, 4-bromo-2-methoxypyridine, pyrazine, 1-methyl-1H-pyrazole, 1,4-dimethyl-1H-pyrazole, 1-methyl-1H-1,2,4-triazole. Key intermediates included [S(S)]-N-[(1S)-2-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-1-(1-methyl-1H-1,2,4-triazol-5-yl)ethyl]-2-methyl-2-propanesulfinamide and a diastereomer, [S(R)]-N-[(1S)-2-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-1-(1-methyl-1H-1,2,4-triazol-5-yl)ethyl]-2-methyl-2-propanesulfinamide. Chiral β-(amino)alkanol derivatives included β-amino-1-methyl-1H-1,2,4-triazole-5-ethanol and (βS)-β-amino-6-methoxy-3-pyridineethanol, (βR)-β-amino-1-methyl-1H-imidazole-1-ethanol, (βS)-β-amino-1-pyrazineethanol, (βR)-β-amino-1-pyrazineethanol.

Synthesis published new progress about 930-36-9. 930-36-9 belongs to pyrazoles-derivatives, auxiliary class Pyrazole, name is 1-Methylpyrazole, and the molecular formula is C4H6N2, Name: 1-Methylpyrazole.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Kelly, Niamh R. published the artcileA simple and environmentally benign synthesis of polypyridine-polycarboxylic acids, Recommanded Product: 4-(1H-Pyrazol-4-yl)pyridine, the publication is Tetrahedron Letters (2011), 52(9), 995-998, database is CAplus.

An oxidation method using dilute nitric acid solutions under solvothermal conditions has been developed to synthesize a series of polypyridine-polycarboxylic acids. It has been successfully applied to a range of Me substituted polypyridines including sym. and asym. 2,2′-bipyridines; 2,2′:6′,2”-terpyridines and; 2,2′:6′,2”:6”,2”’-tetra-pyridines and yields crystalline polypyridine-polycarboxylic acids in a single step. Simple product recovery through filtration yields a recyclable filtrate. More forcing conditions led to demethylation of the polypyridine ligand most probably via decarboxylation. This simple approach avoids potentially harmful metal-based oxidants and negates any issues associated with the disposal of their resultant (hazardous) waste.

Tetrahedron Letters published new progress about 19959-71-8. 19959-71-8 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Pyridine, name is 4-(1H-Pyrazol-4-yl)pyridine, and the molecular formula is C8H7N3, Recommanded Product: 4-(1H-Pyrazol-4-yl)pyridine.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Toure, B. Barry published the artcileToward the Validation of Maternal Embryonic Leucine Zipper Kinase: Discovery, Optimization of Highly Potent and Selective Inhibitors, and Preliminary Biology Insight, HPLC of Formula: 19959-71-8, the publication is Journal of Medicinal Chemistry (2016), 59(10), 4711-4723, database is CAplus and MEDLINE.

MELK kinase has been implicated in playing an important role in tumorigenesis. Our previous studies suggested that MELK is involved in the regulation of cell cycle and its genetic depletion leads to growth inhibition in a subset of high MELK-expressing basal-like breast cancer cell lines. Herein we describe the discovery and optimization of novel MELK inhibitors 8a and 8b that recapitulate the cellular effects observed by short hairpin RNA (shRNA)-mediated MELK knockdown in cellular models. We also discovered a novel fluorine-induced hydrophobic collapse that locked the ligand in its bioactive conformation and led to a 20-fold gain in potency. These novel pharmacol. inhibitors achieved high exposure in vivo and were well tolerated, which may allow further in vivo evaluation.

Journal of Medicinal Chemistry published new progress about 19959-71-8. 19959-71-8 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Pyridine, name is 4-(1H-Pyrazol-4-yl)pyridine, and the molecular formula is C12H10O4S, HPLC of Formula: 19959-71-8.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Bauer, Udo published the artcileDiscovery of 4-hydroxy-1,6-naphthyridine-3-carbonitrile derivatives as novel PDE10A inhibitors, Application In Synthesis of 763120-58-7, the publication is Bioorganic & Medicinal Chemistry Letters (2012), 22(5), 1944-1948, database is CAplus and MEDLINE.

A series of 1,6-naphthyridine-based compounds, e.g., I (R¹ = OEt, Cl, CH₂OH, morpholinomethyl, etc.), was synthesized as potent phosphodiesterase 10A (PDE10A) inhibitors. For example, (bromophenyl)naphthyridinecarbonitrile II reacted with [2-(trifluoromethoxy)phenyl]boronic acid in the presence of PPh₃/Pd(OAc)₂/Na₂CO₃ in THF/H₂O and heated for 30 min to 150°C in a microwave oven to give the biphenyl naphthyridine III. Structure-based chem. modifications of the discovered chemotype served to further improve potency and selectivity over DHODH, laying the foundation for future optimization efforts.

Bioorganic & Medicinal Chemistry Letters published new progress about 763120-58-7. 763120-58-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is 1H-Pyrazole-4-boronic acid, and the molecular formula is C3H5BN2O2, Application In Synthesis of 763120-58-7.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics

Kozlyuk, Natalia published the artcileA fragment-based approach to discovery of Receptor for Advanced Glycation End products inhibitors, Synthetic Route of 763120-58-7, the publication is Proteins: Structure, Function, and Bioinformatics (2021), 89(11), 1399-1412, database is CAplus and MEDLINE.

The Receptor for Advanced Glycation End products (RAGE) is a pattern recognition receptor that signals for inflammation via the NF-κB pathway. RAGE has been pursued as a potential target to suppress symptoms of diabetes and is of interest in a number of other diseases associated with chronic inflammation, such as inflammatory bowel disease and bronchopulmonary dysplasia. Screening and optimization have previously produced small mols. that inhibit the activity of RAGE in cell-based assays, but efforts to develop a therapeutically viable direct-binding RAGE inhibitor have yet to be successful. Here, we show that a fragment-based approach can be applied to discover fundamentally new types of RAGE inhibitors that specifically target the ligand-binding surface. A series of systematic assays of structural stability, solubility, and crystallization were performed to select constructs of the RAGE ligand-binding domain and optimize conditions for NMR-based screening and co-crystallization of RAGE with hit fragments. An NMR-based screen of a highly curated ∼14 000-member fragment library produced 21 fragment leads. Of these, three were selected for elaboration based on structure-activity relationships generated through cycles of structural anal. by X-ray crystallog., structure-guided design principles, and synthetic chem. These results, combined with crystal structures of the first linked fragment compounds, demonstrate the applicability of the fragment-based approach to the discovery of RAGE inhibitors.

Proteins: Structure, Function, and Bioinformatics published new progress about 763120-58-7. 763120-58-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Boronic Acids,Boronic acid and ester, name is 1H-Pyrazole-4-boronic acid, and the molecular formula is C3H5BN2O2, Synthetic Route of 763120-58-7.

Referemce:
https://en.wikipedia.org/wiki/Pyrazole,
Pyrazoles – an overview | ScienceDirect Topics