Day: November 21, 2022

Huang, Shaei published the artcileDevelopment of 6-substituted indolylquinolinones as potent Chek1 kinase inhibitors, Name: 1H-Pyrazole-4-boronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2006), 16(22), 5907-5912, database is CAplus and MEDLINE.

It was hypothesized that the affinity of the indolylquinolinone series for Chek1 kinase would be improved via C6 substitution into the hydrophobic region I (HI) pocket. An efficient route to 6-bromo-3-indolylquinolinone derivative was developed, and this series was rapidly optimized for potency by modification at C6. A general trend was observed among these low nanomolar Chek1 inhibitors that compounds with multiple basic amines, or elevated polar surface area (PSA) exhibited poor cell potency. Minimization of these parameters (basic amines, PSA) resulted in Chek1 inhibitors with improved cell potency, and preliminary pharmacokinetic data are presented for several of these compounds

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

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

Huang, Shaei published the artcileDevelopment of 6-substituted indolylquinolinones as potent Chek1 kinase inhibitors, Name: (1H-Pyrazol-5-yl)boronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2006), 16(22), 5907-5912, database is CAplus and MEDLINE.

It was hypothesized that the affinity of the indolylquinolinone series for Chek1 kinase would be improved via C6 substitution into the hydrophobic region I (HI) pocket. An efficient route to 6-bromo-3-indolylquinolinone derivative was developed, and this series was rapidly optimized for potency by modification at C6. A general trend was observed among these low nanomolar Chek1 inhibitors that compounds with multiple basic amines, or elevated polar surface area (PSA) exhibited poor cell potency. Minimization of these parameters (basic amines, PSA) resulted in Chek1 inhibitors with improved cell potency, and preliminary pharmacokinetic data are presented for several of these compounds

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 C3H5BN2O2, Name: (1H-Pyrazol-5-yl)boronic acid.

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

Li, Yong-xiang published the artcileSolubility of 1-methyl-4-nitropyrazole in seventeen pure solvents at temperatures from 283.15 K to 323.15 K, Product Details of C4H6N2, the publication is Fluid Phase Equilibria (2018), 80-89, database is CAplus.

Knowledge of solubility for 1-methyl-4-nitropyrazole (1-M-4-NP) in different solvents is important for its purification and further theor. studies. In this paper, the solubility of 1-M-4-NP in toluene, 1,2-dichlorobenzene, water, methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, 1-pentanol, 2-pentanol, Me acetate, Et acetate, acetone, butanone, acetic acid and acetonitrile were determined at T = (283.15, 288.15, 293.15, 298.15, 303.15, 308.15, 313.15, 318.15 and 323.15) K under atm. pressure (P = 0.1 MPa) by a gravimetric method. The results showed that the solubility increases with rise of temperature in all selected solvents and the solubility in acetone increases fastest. In alc. solvents, the solubility decreases with the increasing in the number of carbon atoms in the alc. Addnl., melting temperature and fusion enthalpy of 1-M-4-NP were measured by differential scanning calorimetry (DSC). Besides, the solubility values were correlated by the modified Apelblat equation, the polynomial empirical equation, λh equation and NRTL model. Since the correlation coefficients (R²) of the four models are greater than 0.9900 and the largest values of the root-mean-square was 7.00 × 10^-2, four correlation models can be adopted to correlate the solubility data. On the basis of the NRTL model, the dissolution thermodn. properties, including enthalpy, entropy and Gibbs energy were calculated and discussed as well according to the exptl. data, from which we conclude that the dissolution of 1-M-4-NP is an spontaneous process. Furthermore, solubility values and thermodn. relations of 1-M-4-NP in selected solvents would be invoked as fundamental data and models regarding the purification process of 1-M-4-NP.

Fluid Phase Equilibria 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, Product Details of C4H6N2.

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

Nguyen, Duc-Huy T. published the artcileCdc42 regulates branching in angiogenic sprouting in vitro, Recommanded Product: 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, the publication is Microcirculation (Oxford, United Kingdom) (2017), 24(5), n/a, database is CAplus and MEDLINE.

The morphogenetic events that occur during angiogenic sprouting involve several members of the Rho family of GTPases, including Cdc42. However, the precise roles of Cdc42 in angiogenic sprouting have been difficult to elucidate owing to the lack of models to study these events in vitro. Here, we aim to identify the roles of Cdc42 in branching morphogenesis in angiogenesis. Using a 3D biomimetic model of angiogenesis in vitro, where endothelial cells were seeded inside a cylindrical channel within collagen gel and sprouted from the channel in response to a defined biochem. gradient of angiogenic factors, we inhibited Cdc42 activity with a small mol. inhibitor ML141 and examined the effects of Cdc42 on the morphogenetic processes of angiogenic sprouting. We find that partial inhibition of Cdc42 had minimal effects on directional migration of endothelial cells, but led to fewer branching events without affecting the length of these branches. We also observed that antagonizing Cdc42 reduced collective migration in favor of single cell migration. Addnl., Cdc42 also regulated the initiation of filopodial extensions in endothelial tip cells. Our findings suggest that Cdc42 can affect multiple morphogenetic processes during angiogenic sprouting and ultimately impact the architecture of the vasculature.

Microcirculation (Oxford, United Kingdom) 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, Recommanded Product: 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide.

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

Shan, Yuanyuan published the artcileDiscovery of novel VEGFR-2 inhibitors. Exploration of diverse hinge-binding fragments via core-refining approach, Recommanded Product: 1H-Pyrazole-4-boronic acid, the publication is European Journal of Medicinal Chemistry (2015), 80-90, database is CAplus and MEDLINE.

Pathol. angiogenesis plays a critical role in numerous diseases including malignancy. VEGFR-2 is the central regulators in angiogenesis and has become a promising target for anticancer drug design. The authors have identified a novel biphenyl-aryl urea incorporated with salicyladoxime (BPS-7) as potent VEGFR-2 inhibitor. As a continuation to the previous research, various aromatic-heterocyclic were introduced as hinge-binding fragment via a core-refining approach. Interestingly, many compounds exhibited comparable VEGFR-2 inhibition to Sorafenib. In particular, I and II displayed excellent VEGFR-2 inhibitory activity with IC₅₀ values of 0.50 nM and 0.79 nM, resp. Several title compounds showed considerable antiproliferative activity against A549 and SMMC-7721 cells. In addition, mol. docking was performed to rationalize the efficiency of the better compounds These results will be instructive for further inhibitor design and optimization.

European 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 C27H39ClN2, Recommanded Product: 1H-Pyrazole-4-boronic acid.

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

Audubert, Clement published the artcileBatch and Continuous-Flow One-Pot Processes using Amine Diazotization to Produce Silylated Diazo Reagents, Category: pyrazoles-derivatives, the publication is Angewandte Chemie, International Edition (2017), 56(22), 6294-6297, database is CAplus and MEDLINE.

A novel synthesis of trimethylsilyldiazomethane (TMSCHN₂) by diazotization of trimethylsilylmethylamine (TMSCH₂NH₂) is reported using batch and continuous flow syntheses. The latter affords a daily production of 275 g (2.4 mol) of TMSCHN₂. Other silylated methylamines were also successfully reacted under the developed reaction conditions to furnish various silicon-bearing diazomethane reagents. The applicability of the process is highlighted by disclosure of batch and continuous flow one-pot esterification and 1,3-dipolar cycloaddition processes. Furthermore, the high-yielding esterification of carboxylic acids with silylated and substituted methylamines in continuous flow is disclosed. Finally, work-up and purification procedures are reported for the preparation of a 2-MeTHF solution of TMSCHN₂, which can be used in rhodium-catalyzed methylenation and homologation reactions.

Angewandte Chemie, International Edition published new progress about 1297537-37-1. 1297537-37-1 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Chloride,Nitrile,Benzene, name is 2-Chloro-4-(1H-pyrazol-5-yl)benzonitrile, and the molecular formula is C10H6ClN3, Category: pyrazoles-derivatives.

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

Brzozowski, Zdzislaw published the artcileDerivatives of pyrazole-1-carboxylic acid. V. Syntheses of some derivatives of N-{4-[2-(pyrazole-1-carboxamido)ethyl]benzensulfonyl}-2-pyrazoline-1-carboxamide, Category: pyrazoles-derivatives, the publication is Acta Poloniae Pharmaceutica (1982), 39(1-3), 15-19, database is CAplus.

Twenty-five title compounds I (R-R⁶ = H, Me, and Et in various combinations) were prepared in 17-73% yields in the reaction of II with appropriately substituted pyrazole-1-carboxylic acid chlorides in the presence of 40% aqueous NaOH. Nine of them showed a moderate hypoglycemic activity in exptl. rats.

Acta Poloniae Pharmaceutica published new progress about 53355-55-8. 53355-55-8 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Chloride,acyl chloride,Amide, name is 1H-Pyrazole-1-carbonyl chloride, and the molecular formula is C4H3ClN2O, Category: pyrazoles-derivatives.

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

Nasveschuk, Christopher G. published the artcileDiscovery and Optimization of Tetramethylpiperidinyl Benzamides as Inhibitors of EZH2, Name: 1H-Pyrazole-4-boronic acid, the publication is ACS Medicinal Chemistry Letters (2014), 5(4), 378-383, database is CAplus and MEDLINE.

The identification and development of a novel series of small mol. Enhancer of Zeste Homolog 2 (EZH2) inhibitors is described. A concise and modular synthesis enabled the rapid development of structure-activity relationships, which led to the identification of I as a potent, SAM-competitive inhibitor of EZH2 that dose-dependently decreased global H3K27me3 in KARPAS-422 lymphoma cells.

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

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

Cordero, Diana published the artcileSmall Molecule Inhibitors Limit Endothelial Cell Invasion by Staphylococcus aureus, Category: pyrazoles-derivatives, the publication is Current Pharmaceutical Biotechnology (2014), 15(8), 727-737, database is CAplus and MEDLINE.

Staphylococcus aureus is a leading causative agent in sepsis, endocarditis, and pneumonia. An emerging concept is that prognosis worsens when the infecting S. aureus strain has the capacity to not only colonize tissue as an extracellular pathogen, but to invade host cells and establish intracellular bacterial populations. In previous work, we identified host CDC42 as a central regulator of endothelial cell invasion by S. aureus. In the current work, we report that ML 141, a first-in-class CDC42 inhibitor, decreases invasion and resultant pathogenesis in a dose-dependent and reversible manner. Inhibition was found to be due in part to decreased remodeling of actin that potentially drives endocytic uptake of bacteria/fibronectin/integrin complexes. ML 141 decreased binding to fibronectin at these complexes, thereby limiting a key pathogenic mechanism used by S. aureus to invade. Structural analogs of ML 141 were synthesized (designated as the RSM series) and a subset identified that inhibit invasion through non-cytotoxic and non-bactericidal mechanisms. Our results support the development of adjunctive therapeutics targeting host CDC42 for mitigating invasive infection at the level of the host.

Current Pharmaceutical Biotechnology 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, Category: pyrazoles-derivatives.

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

Tironi, Carla published the artcilePyrazole sulfanilamides: nitro derivatives of 1-phenyl-3-sulfanilamidopyrazole, Recommanded Product: 3-Acetamidopyrazole, the publication is Farmaco (1990), 45(4), 473-8, database is CAplus and MEDLINE.

The synthesis and structural characterization of 3 title compounds I (R = 2-O₂N, 3-O₂N, 4-O₂N) from 3(5)-acetamidopyrazole and RC₆H₄Br are reported. All derivatives are analyzed by ¹H and ¹³C NMR spectroscopy. The min. inhibiting concentration values obtained against Escherichia coli are briefly discussed in terms of structure-activity relationship.

Farmaco published new progress about 3553-12-6. 3553-12-6 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Amine,Amide, name is 3-Acetamidopyrazole, and the molecular formula is C10H11FN2O2S, Recommanded Product: 3-Acetamidopyrazole.

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