Month: November 2022

He, Yuanjun published the artcileSynthesis and SAR of novel quinazolines as potent and brain-penetrant c-jun N-terminal kinase (JNK) inhibitors, Recommanded Product: 1H-Pyrazole-4-boronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2011), 21(6), 1719-1723, database is CAplus and MEDLINE.

Quinazoline I (R = H) was discovered as a novel c-jun N-terminal kinase (JNK) inhibitor with good brain penetration and pharmacokinetic (PK) properties. A number of analogs which were potent both in the biochem. and cellular assays were discovered. Quinazoline I (R = Cl)(II) was found to be a potent JNK3 inhibitor (IC₅₀ = 40 nM), with >500-fold selectivity over p38, and had good PK and brain penetration properties. With these properties, II is considered a potential candidate for in vivo evaluation.

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, Recommanded Product: 1H-Pyrazole-4-boronic acid.

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

Antonow, Dyeison published the artcileStructure-Activity Relationships of Monomeric C2-Aryl Pyrrolo[2,1-c][1,4]benzodiazepine (PBD) Antitumor Agents, Recommanded Product: 1H-Pyrazole-4-boronic acid, the publication is Journal of Medicinal Chemistry (2010), 53(7), 2927-2941, database is CAplus and MEDLINE.

A comprehensive SAR investigation of the C2-position of pyrrolo[2,1-c][1,4]benzodiazepine (PBD) monomer antitumor agents is reported, establishing the mol. requirements for optimal in vitro cytotoxicity and DNA-binding affinity. Both carbocyclic and heterocyclic C2-aryl substituents have been studied ranging from single aryl rings to fused ring systems, and also styryl substituents, establishing across a library of 80 analogs that C2-aryl and styryl substituents significantly enhance both DNA-binding affinity and in vitro cytotoxicity, with a correlation between the two. The optimal C2-grouping for both DNA-binding affinity and cytotoxicity was found to be the C2-quinolinyl moiety which, according to mol. modeling, is due to the overall fit of the mol. in the DNA minor groove, and potential specific contacts with functional groups in the floor and walls of the groove. This analog (I) was shown to delay tumor growth in a HCT-116 (bowel) human tumor xenograft model.

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, Recommanded Product: 1H-Pyrazole-4-boronic acid.

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

Schmitt, Christian published the artcileDesign and synthesis of a library of lead-like 2,4-bisheterocyclic substituted thiophenes as selective Dyrk/Clk inhibitors, Category: pyrazoles-derivatives, the publication is PLoS One (2014), 9(3), e87851/1-e87851/20, 20 pp., database is CAplus and MEDLINE.

The Dyrk family of protein kinases is implicated in the pathogenesis of several diseases, including cancer and neurodegeneration. Pharmacol. inhibitors were mainly described for Dyrk1A so far, but in fewer cases for Dyrk1B, Dyrk2 or other isoforms. Herein, we report the development and optimization of 2,4-bisheterocyclic substituted thiophenes as a novel class of Dyrk inhibitors. The optimized hit compounds displayed favorable pharmacokinetic properties and high ligand efficiencies, and inhibited Dyrk1B in intact cells. In a larger selectivity screen, only Clk1 and Clk4 were identified as addnl. targets of compound 48, but no other kinases frequently reported as off-targets. Interestingly, Dyrk1A is implicated in the regulation of alternative splicing, a function shared with Clk1/Clk4; thus, some of the dual inhibitors might be useful as efficient splicing modulators. A further compound (29) inhibited Dyrk1A and 1B with an IC50 of 130 nM, showing a moderate selectivity over Dyrk2. Since penetration of the central nervous system (CNS) seems possible based on the physicochem. properties, this compound might serve as a lead for the development of potential therapeutic agents against glioblastoma. Furthermore, an inhibitor selective for Dyrk2 (24) was also identified, which might be are suitable as a pharmacol. tool to dissect Dyrk2 isoform-mediated functions.

PLoS One 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

Pahontu, Elena published the artcileSynthesis, characterization, crystal structure and antiproliferative activity studies of Cu(II), Ni(II) and Co(II) complexes with 4-benzoyl-5-pyrazolones derived compounds, Category: pyrazoles-derivatives, the publication is Journal of Organometallic Chemistry (2017), 44-55, database is CAplus.

Eleven new Cu(II), Ni(II), and Co(II) complexes (1–11) with thiosemicarbazones 1-phenyl-3-methyl-4-benzoyl-5-pyrazolone-4-R thiosemicarbazone (R = CH₃,C₆H₅, C₅H₅N) (HL^1-3) were synthesized. The ligands was characterized by FT- IR, ¹H NMR, ¹³C NMR spectroscopy and x-ray diffraction. All the complexes were characterized by UV-visible and FTIR spectroscopy, molar conductivity, magnetic susceptibility measurements and elemental anal. The Cu (II) complexes were studied by EPR spectroscopy. Also, the crystal structures of copper and nickel complexes 1, 3, 6 and 7 were determined by single-crystal x-ray diffraction anal. The Cu atom exhibits a distorted square-planar coordination environment in the complex 1 provided by one mol. of deprotonated ligand and one chloride anion, while in the complex 6 show a distorted square-pyramidal coordination geometry. In the complexes 3 and 7, the Ni atom exhibits a slightly distorted octahedral O₂N₂S₂ coordination provided by two mols. of tridentate deprotonated ligand. The in vitro antiproliferative activity of the ligands and metal complexes was screened on human leukemia HL-60 cells. It was noticed a significant inhibition of growth of malignant cells HL-60 in the case Cu complexes 2 and 5 with IC₅₀ values of 0.24 μM and 0.36 μM, resp.

Journal of Organometallic Chemistry 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, Category: pyrazoles-derivatives.

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

Zhang, Lingzhi published the artcileDiscovery of novel dual extracellular regulated protein kinases (ERK) and phosphoinositide 3-kinase (PI3K) inhibitors as a promising strategy for cancer therapy, Related Products of pyrazoles-derivatives, the publication is Molecules (2020), 25(23), 5693, database is CAplus and MEDLINE.

The scaffold-hopping generation of a series of 1H-pyrazolo[3,4-d]pyrimidines I (R¹ = 2-methylpyridin-4-yl, 1-methyl-1H-pyrazol-4-yl; R² = Bn, cyclopentyl) dual ERK/PI3K inhibitors was reported. 1-(7-(1H-Pyrazol-4-yl)pyrido[3,2-d]pyrimidin-2-yl)-3-cyclopentylurea was the most promising candidate, with potent inhibitory activities against both ERK2 and PI3Kα which displays superior anti-proliferative profiles against HCT116 and HEC1B cancer cells. Meanwhile, 1-(7-(1H-pyrazol-4-yl)pyrido[3,2-d]pyrimidin-2-yl)-3-cyclopentylurea possessed acceptable pharmacokinetic profiles and showed more efficacious anti-tumor activity than GDDC-0980 and the corresponding drug combination (BVD-523 + GDDC-0980) in HCT-116 xenograft model, with a tumor growth inhibitory rate of 51% without causing observable toxic effects. All the results indicated that 1-(7-(1H-pyrazol-4-yl)pyrido[3,2-d]pyrimidin-2-yl)-3-cyclopentylurea was a highly effective anticancer compound and provided a promising basis for further optimization towards dual ERK/PI3K inhibitors.

Molecules 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 C10H2F12NiO4, Related Products of pyrazoles-derivatives.

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

Wang, Zhaogai published the artcileConcentrating sulphur-containing flavour from Toona sinensis shoots using corn oil with and without aqueous dispersion, Recommanded Product: 1-Methylpyrazole, the publication is International Journal of Food Science and Technology (2022), 57(3), 1644-1653, database is CAplus.

Toona sinensis (TS) shoot is a seasonal and quick deteriorating vegetable with unique alliaceous flavor. In this study, corn oil was used to concentration the sulfur-containing compounds responsible for the unique TS flavor with and without aq dispersion. The level of sulfur-containing compounds in TS shoots was 0.32μg g-1 and concentratio to 2.34μg g-1 in the corn oil with aq dispersion. The sulfur-containing compounds, trans-2-Mercapto-3,4-dimethyl-2,3-dihydrothiophene and (E,Z)-Di-1-propenyldisulfide, were identified in the corn oil, while they were not detected in the oil without aq dispersion. Based on sensory and electronic nose anal., the aroma of corn oil with aq medium extraction had stronger alliaceous aroma than TS shoots and the extraction corn oil without aq dispersion. With aq dispersion assistance, the sulfur-containing aroma compounds in TS shoots were effectively concentration in corn oil. The flavor-enriched oil could serve as a flavor ingredient to deliver TS shoots aroma for different food applications.

International Journal of Food Science and Technology 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 C8H8O3, Recommanded Product: 1-Methylpyrazole.

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

Liu, Lingling published the artcileCdc42-mediated supracellular cytoskeleton induced cancer cell migration under low shear stress, HPLC of Formula: 71203-35-5, the publication is Biochemical and Biophysical Research Communications (2019), 519(1), 134-140, database is CAplus and MEDLINE.

Tumor microenvironment is composed of biol., chem. and phys. factors. Mech. factors are more and more focused these years. Therefore, mimicking mech. factors’ contribution to cancer cell malignancy will greatly improve the advance in this field. Although the induced malignant behaviors are present under many stimuli such as growth or inflammatory factors, the cell key phys. migration mechanisms are still missing. In this study, we identify that low shear stress significantly promotes the formation of needle-shaped membrane protrusions, which is called filopodia and important for the sense and interact of a cell with extracellular matrix in the tumor microenvironment. Under low shear stress, the migration is promoted while it is inhibited in the presence of ROCK inhibitor Y27632, which could abolish the F-actin network. Using cell imaging, we further unravel that key to these protrusions is Cell division cycle 42 (Cdc42) dependent. After Cdc42 activation, the filopodia is more and longer, acting as massagers to pass the information from a cell to the microenvironment for its malignant phenotype. In the Cdc42 inhibition, the filopodia is greatly reduced. Moreover, small GTPases Cdc42 rather than Rac1 and Rho directly controls the filopodia formation. Our work highlights that low shear stress and Cdc42 activation are sufficient to promote filopodia formation, it not only points out the novel structure for cancer progression but also provides the exptl. phys. basis for the efficient drug anti-cancer strategies.

Biochemical and Biophysical Research Communications published new progress about 71203-35-5. 71203-35-5 belongs to pyrazoles-derivatives, auxiliary class GPCR/G Protein,Ras, name is 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, and the molecular formula is C22H21N3O3S, HPLC of Formula: 71203-35-5.

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

Zhu, Song-Lei published the artcileA simple and efficient one-pot synthesis of spirooxindoles in water under microwave irradiation conditions, HPLC of Formula: 14580-22-4, the publication is Letters in Organic Chemistry (2008), 5(4), 319-323, database is CAplus.

A simple and efficient method for the synthesis of spirooxindoles derivatives by one-pot reactions of isatins, activated methylene reagents, and activated carbonyl compounds in water under microwave irradiation was reported. This protocol has the advantages of short reaction time, high yields, easy work-up procedure, and environmentally benign characters.

Letters in Organic Chemistry published new progress about 14580-22-4. 14580-22-4 belongs to pyrazoles-derivatives, auxiliary class Organic Pigment, name is 1-(2-Chlorophenyl)-3-methyl-5-pyrazolone, and the molecular formula is C7H8FNO2S, HPLC of Formula: 14580-22-4.

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

Gowri, M. published the artcileCrystal Structure and Characterization of Novel Schiff Base: (Z)-4-(((2-hydroxy phenyl)amino)(phenyl)methylene)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one, SDS of cas: 4551-69-3, the publication is Molecular Crystals and Liquid Crystals (2012), 569(1), 151-161, database is CAplus.

The crystal structure of (Z)-4-(((2-hydroxy phenyl)amino)(phenyl)methylene)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one was investigated. Weak interactions including intermol. forces, metal-ion coordination, electrostatic forces, van der Waals interactions, and donor-acceptor interactions were responsible for the organized entities of higher complexity. Single crystal X-ray diffraction (XRD) showed that the compound crystallized in the triclinic crystal system with space group P1̅ with a = 7.1822(3) , b = 11.0015(4), c = 13.6353(5) A; α = 111.715(10)°, β = 92.255 (2)°, γ = 106.002 (2)°, and Z = 2. FTIR, UV-Vis, ¹H NMR, and CHN were employed to characterize the crystal. Thermal stability and the weak interactions among the neutral entities were also investigated.

Molecular Crystals and Liquid Crystals 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, SDS of cas: 4551-69-3.

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

Kim, Og Soon published the artcileSynthesis of Fluorescent Indazoles by Palladium-Catalyzed Benzannulation of Pyrazoles with Alkynes, HPLC of Formula: 930-36-9, the publication is Organic Letters (2017), 19(6), 1450-1453, database is CAplus and MEDLINE.

Pentasubstituted indazoles such as I (R = H, Me, t-Bu, MeO, EtO₂C, F, Cl) were prepared in 34-84% yields by oxidative benzannulation reactions of pyrazoles such as 1-methylpyrazole with sym. internal alkynes such as 4-(4-RC₆H₄CC)C₆H₄R (R = H, Me, t-Bu, MeO, EtO₂C, F, Cl) in the presence of Pd(OAc)₂ and Cu(OAc)₂ in 1,4-dioxane or by benzannulation of substituted 4-bromopyrazoles with sym. internal alkynes in the presence of Pd(OAc)₂, t-Bu₃P•HBF₄, K₂CO₃, and pivalic acid in toluene; unsym. internal alkynes gave mixtures of regioisomers. 1,2-Disubstituted imidazoles also underwent oxidative benzannulation with diphenylacetylene in the presence of Pd(OAc)₂ and Cu(OAc)₂ in 1,4-dioxane to yield tetraphenylbenzimidazoles in 41-50% yields. The fluorescence and optical bandgaps of I (R = H, t-Bu, MeO, EtO₂C, F, Cl) were determined The structure of I (R = H) was determined by X-ray crystallog.

Organic 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, HPLC of Formula: 930-36-9.

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