Month: December 2022

Xu, Ying-zi published the artcileDesign and synthesis of thiophene dihydroisoquinolines as novel BACE1 inhibitors, Recommanded Product: (1H-Pyrazol-5-yl)boronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2013), 23(10), 3075-3080, database is CAplus and MEDLINE.

Utilizing a structure based design approach, combined with extensive medicinal chem. execution, highly selective, potent and novel BACE1 inhibitor I (BACE1 Alpha assay IC₅₀ = 8 nM) was made from a weak μM potency hit in an extremely efficient way. The detailed SAR and general design approaches will be discussed.

Bioorganic & Medicinal Chemistry Letters published new progress about 724710-02-5. 724710-02-5 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Pyrazole,Boronic Acids,Boronic acid and ester, name is (1H-Pyrazol-5-yl)boronic acid, and the molecular formula is C8H6KNO4S, Recommanded Product: (1H-Pyrazol-5-yl)boronic acid.

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

Li, Weipeng published the artcileCooperative Au/Ag Dual-Catalyzed Cross-Dehydrogenative Biaryl Coupling: Reaction Development and Mechanistic Insight, Synthetic Route of 930-36-9, the publication is Journal of the American Chemical Society (2019), 141(7), 3187-3197, database is CAplus and MEDLINE.

In the presence of (Me₂S)AuCl and AgOAc, pyrazoles such as 1-phenylpyrazole underwent chemoselective and regioselective oxidative dehydrogenative coupling reactions with fluorinated arenes and pyridines such as 2,3,5,6-tetrafluoropyridine mediated by PhI(OAc)₂ in 1,4-dioxane to yield (fluoroaryl)pyrazoles such as I. The mechanism of the oxidative coupling reaction was studied by determination of the reaction kinetics, kinetic isotope effects, and deuterium exchange, by generation and preparation of gold and silver complexes as potential intermediates, and by DFT calculations of transition state structures and energies for arene metalation, transmetalation, and reductive elimination reactions. Silver acetate is determined to be is the actual catalyst for C-H activation of electron-poor arenes, rather than gold(I) complexes. A mechanism of gold/silver dual catalysis is proposed, in which silver is responsible for the activation of electron-poor fluoroarenes via a concerted metalation-deprotonation pathway, and gold is responsible for the activation of electron-rich pyrazoles via an electrophilic aromatic substitution process. Kinetic studies reveal that C-H activation of pyrazoles by fluoroarylgold complexes is most likely the rate-limiting step.

Journal of the American Chemical Society 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, Synthetic Route of 930-36-9.

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

Li, Weipeng published the artcileCooperative Au/Ag Dual-Catalyzed Cross-Dehydrogenative Biaryl Coupling: Reaction Development and Mechanistic Insight, Category: pyrazoles-derivatives, the publication is Journal of the American Chemical Society (2019), 141(7), 3187-3197, database is CAplus and MEDLINE.

In the presence of (Me₂S)AuCl and AgOAc, pyrazoles such as 1-phenylpyrazole underwent chemoselective and regioselective oxidative dehydrogenative coupling reactions with fluorinated arenes and pyridines such as 2,3,5,6-tetrafluoropyridine mediated by PhI(OAc)₂ in 1,4-dioxane to yield (fluoroaryl)pyrazoles such as I. The mechanism of the oxidative coupling reaction was studied by determination of the reaction kinetics, kinetic isotope effects, and deuterium exchange, by generation and preparation of gold and silver complexes as potential intermediates, and by DFT calculations of transition state structures and energies for arene metalation, transmetalation, and reductive elimination reactions. Silver acetate is determined to be is the actual catalyst for C-H activation of electron-poor arenes, rather than gold(I) complexes. A mechanism of gold/silver dual catalysis is proposed, in which silver is responsible for the activation of electron-poor fluoroarenes via a concerted metalation-deprotonation pathway, and gold is responsible for the activation of electron-rich pyrazoles via an electrophilic aromatic substitution process. Kinetic studies reveal that C-H activation of pyrazoles by fluoroarylgold complexes is most likely the rate-limiting step.

Journal of the American Chemical Society published new progress about 1268520-92-8. 1268520-92-8 belongs to pyrazoles-derivatives, auxiliary class Other Aromatic Heterocyclic,Chloride, name is 4-Chloro-1-methyl-1H-pyrazolo[3,4-b]pyridine, and the molecular formula is C7H6ClN3, Category: pyrazoles-derivatives.

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

Tong, Jin published the artcileProgrammable self-assembly of homo- or hetero-metallomacrocycles using 4-(1H-pyrazolyl-4-yl)pyridine, Recommanded Product: 4-(1H-Pyrazol-4-yl)pyridine, the publication is Chemical Communications (Cambridge, United Kingdom) (2012), 48(43), 5343-5345, database is CAplus and MEDLINE.

The dimetallic [M₂(bpy)₂(NO₃)₂](NO₃)₂ moieties (M = Pd(II) or Pt(II)) react preferentially at the pyrazolyl end of the pyridyl-pyrazole ligand, giving rise to dimetallic corners. Subsequently, the dimetallic corner building blocks featuring two pyridine donors are coordinated by monometallic [M(bpy)(NO₃)₂] moieties (M = Pd(II) or Pt(II)) to form homo- or hetero-metallomacrocycles.

Chemical Communications (Cambridge, United Kingdom) 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 C3H5BN2O2, Recommanded Product: 4-(1H-Pyrazol-4-yl)pyridine.

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

Ma, Xue-lin published the artcileCondensation reaction of aromatic aldehydes and 1-phenyi-3-methyl-4-benzoyl-pyrazolone catalysted by phosphotungstic acid loaded on 404 organic support, Name: 4-Benzoyl-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one, the publication is Huaxue Shiji (2014), 36(7), 646-650, database is CAplus.

Many loaded-catalysts are applied to the Mannich reaction, but they have disadvantages such as low yield, unstability of loaded rate and asking for long time. 404 Organic support loaded phosphotungstic acid was synthesized by the reaction of 404 organic support and phosphotungstic acid in CC14. The effects of different reaction conditions on the yields were investigated. The condensation reaction of aromatic aldehydes and 1-phenyl-3-methyl-4-benzoyl-pyrazolone was catalyzed by 404 organic support loaded phosphotungstic acid. Simultaneously the products were determined by IR, ¹HNMR and elemental anal. The catalyst was provided with stable cubic crystal spatial structure and good dispersion. This protocol has advantages of stability of loaded rate, short time, mild condition, high yield, high selectivity, simple work-up, environmental friendly procedure and the catalyst can be reused.

Huaxue Shiji published new progress about 4551-69-3. 4551-69-3 belongs to pyrazoles-derivatives, auxiliary class Benzenes, name is 4-Benzoyl-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one, and the molecular formula is C17H14N2O2, Name: 4-Benzoyl-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one.

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

Sessions, E. Hampton published the artcileBenzimidazole- and benzoxazole-based inhibitors of Rho kinase, Safety of 1H-Pyrazole-4-boronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2008), 18(24), 6390-6393, database is CAplus and MEDLINE.

Inhibitors of Rho kinase have been developed based on two distinct scaffolds, benzimidazoles, and benzoxazoles. SAR studies and efforts to optimize the initial lead compounds are described. Novel selective inhibitors of ROCK-II with excellent potency in both enzyme and cell-based assays were obtained. These inhibitors possess good microsomal stability, low cytochrome P 450 inhibitions and good oral bioavailability.

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 C6H3ClFNO2, Safety of 1H-Pyrazole-4-boronic acid.

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

Feng, Yangbo published the artcileDiscovery of Substituted 4-(Pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as Potent and Highly Selective Rho Kinase (ROCK-II) Inhibitors, Name: 1H-Pyrazole-4-boronic acid, the publication is Journal of Medicinal Chemistry (2008), 51(21), 6642-6645, database is CAplus and MEDLINE.

The identification of a new class of potent and selective ROCK-II inhibitors is presented. Compound SR-3677 (I) had an IC₅₀ of ∼3 nM in enzyme and cell based assays and had an off-target hit rate of 1.4% against 353 kinases, and inhibited only 3 out of 70 nonkinase enzymes and receptors. Pharmacol. studies showed that I was efficacious in both, increasing ex vivo aqueous humor outflow in porcine eyes and inhibiting myosin light chain phosphorylation.

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, Name: 1H-Pyrazole-4-boronic acid.

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

Duan, Yongbin published the artcileDesign, synthesis and biological evaluation of benzothiazoles as highly potent ROCK inhibitors through molecular docking and free energy calculations, Category: pyrazoles-derivatives, the publication is Gaodeng Xuexiao Huaxue Xuebao (2017), 38(9), 1568-1577, database is CAplus.

Rock has been considered to provide a pharmacol. strategy for preventing and treating multiple sclerosis, pulmonary hypertension, glaucoma, cardiovascular disease, erectile dysfunction and cancer. With 3 previously reported and benzothiazole-based ROCK inhibitors (1-3) as the research targets, the structure-activity relationship (SAR) was preliminary revealed from amino acid level by mol. docking after obtaining the stable ROCK2-ligand complexes in the binding pocket through mol. dynamic simulations. Then MM/GBSA free energy calculations of compounds 1-3 showed that there was good correlation between binding affinity (ΔG_bind) and inhibitory activities, and van der Waals interaction (ΔG_VDW) contributing to ΔG_bind most. And the key amino acids with outstanding contribution for high inhibition were obtained through free energy anal. Finally, 3 series of benzothiazoles (D1-D10) were designed according to the results of mol. docking and free energy calculations In the biol. evaluation, compounds D1-D10 exhibited 2-105 nmol/L IC₅₀ values against ROCK2 and 11-288 nmol/L IC₅₀ values against ROCK1. Compounds D3-D5 exhibited higher metabolic stability than reported compounds 1 and 3 in human liver microsome studies. This work not only gave theor. guidance for the design of highly potent ROCK, but also offered a series of highly active ROCK inhibitors with intellectual property right for fundamental research and application of ROCK.

Gaodeng Xuexiao Huaxue Xuebao 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, Category: pyrazoles-derivatives.

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

Goeksu, Haydar published the artcileHighly efficient and monodisperse graphene oxide furnished Ru/Pd nanoparticles for the dehalogenation of aryl halides via ammonia borane, Recommanded Product: 1-Methylpyrazole, the publication is ChemistrySelect (2016), 1(5), 953-958, database is CAplus.

Highly monodisperse graphene oxide-supported Ru/Pd nanoparticles (RuPd@GO NPs) was reproducibly and easily synthesized by microwave assisted method. RuPd@GO NPs were performed for dehalogenation of arylhalides in the presence of ammonia borane in a mild condition as novel, highly efficient and exceptional reusable heterogeneous catalyst. The novel materials were characterized by transmission electron microscopy (TEM), the high resolution electron micrograph (HRTEM), X-ray diffraction (XRD) and XPS. The results showed that the prepared catalysts were highly crystalline, monodisperse and colloidally stable. The current one-pot catalytic process was described as a new methodol. for dehalogenation of arylhalides which was assessed as a quite simple, eco-friendly and highly efficient as well as exceptional reusable. All products were provided with one of the highest yield and the shortest time in the presence of novel RuPd@GO NPs due to the the synergistic effect of Ru and Pd. Synthesis process comes with a facile and eco-friendly option to RuPd@GO NPs, allowed further scrutiny of current catalysts for numerous other chem. reactions.

ChemistrySelect 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, Recommanded Product: 1-Methylpyrazole.

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

Persson, Tobias published the artcilePyrazole carboxamides and carboxylic acids as protein kinase inhibitors in aberrant eukaryotic signal transduction: Induction of growth arrest in MCF-7 cancer cells, Quality Control of 13599-22-9, the publication is Organic & Biomolecular Chemistry (2007), 5(24), 3963-3970, database is CAplus and MEDLINE.

Densely functionalized pyrazolecarboxamides, e.g. I, and pyrazolecarboxylic acids were prepared through saponification and transamidation of ester-functionalized pyrazoles. This synthetic protocol allowed for three diversifying steps in which appendages on the pyrazole scaffold were adjusted to optimize inhibition of protein kinases. Thirty-five analogs were tested in CK2, AKT1, PKA, PKCα, and SAPK2a (p38) kinase inhibition bioassays. Blocking of these kinases may lead to effective therapies for treating inflammatory diseases and cancer. In order to investigate potential biol. activity, MCF-7 human breast cancer cells were incubated with the most promising derivatives Two analogs caused changes in MCF-7 cell growth, one of them through cell cycle arrest demonstrated by cell cycle anal.

Organic & Biomolecular Chemistry published new progress about 13599-22-9. 13599-22-9 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Carboxylic acid,Benzene, name is 1,5-Diphenyl-1H-pyrazole-3-carboxylic acid, and the molecular formula is C16H12N2O2, Quality Control of 13599-22-9.

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