Month: December 2022

Li, Yan published the artcileAutoT&T v.2: An Efficient and Versatile Tool for Lead Structure Generation and Optimization, Recommanded Product: 1-(3-Chlorophenyl)pyrazole-4-boronic acid, the publication is Journal of Chemical Information and Modeling (2016), 56(2), 435-453, database is CAplus and MEDLINE.

In structure-based drug design, automated de novo design methods are helpful tools for lead discovery as well as lead optimization. In a previous study the authors reported a new de novo design method, namely, Automatic Tailoring and Transplanting (AutoT&T). It overcomes some intrinsic problems in conventional fragment-based buildup methods. In this study, the authors describe an upgraded version, namely, AutoT&T2. Structural operations conducted by AutoT&T2 have been largely optimized by introducing several new algorithms. As a result, its overall speed in multiround optimization jobs has been improved by a few thousand fold. With this improvement, it is now practical to conduct structural crossover among multiple lead mols. using AutoT&T2. Three different test cases are described in this study that demonstrate the new features and versatile applications of AutoT&T2. The AutoT&T2 software suite is available to the public. Besides, a Web portal for running AutoT&T2 online is provided at http://www.sioc-ccbg.ac.cn/software/att2 for testing.

Journal of Chemical Information and Modeling published new progress about 1072945-88-0. 1072945-88-0 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Chloride,Boronic acid and ester,Benzene,Boronic Acids,Boronic Acids,Boronic acid and ester,, name is 1-(3-Chlorophenyl)pyrazole-4-boronic acid, and the molecular formula is C9H8BClN2O2, Recommanded Product: 1-(3-Chlorophenyl)pyrazole-4-boronic acid.

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

Ran, Xu published the artcileStructure-Based Design of γ-Carboline Analogues as Potent and Specific BET Bromodomain Inhibitors, Computed Properties of 763120-58-7, the publication is Journal of Medicinal Chemistry (2015), 58(12), 4927-4939, database is CAplus and MEDLINE.

Small-mol. inhibitors of bromodomain and extra terminal proteins (BET), including BRD2, BRD3, and BRD4 proteins have therapeutic potential for the treatment of human cancers and other diseases and conditions. In this paper, the authors report the design, synthesis, and evaluation of γ-carboline-containing compounds as a new class of small-mol. BET inhibitors. The most potent inhibitor I (RX-37) obtained from this study binds to BET bromodomain proteins (BRD2, BRD3, and BRD4) with K_i values of 3.2-24.7 nM and demonstrates high selectivity over other non-BET bromodomain-containing proteins. Compound I potently and selectively inhibits cell growth in human acute leukemia cell lines harboring the rearranged mixed lineage leukemia 1 gene. The authors have determined a cocrystal structure of I in complex with BRD4 BD2 at 1.4 Å resolution, which provides a solid structural basis for the compound’s high binding affinity and for its further structure-based optimization. Compound I represents a promising lead compound for the development of a new class of therapeutics for the treatment of human cancer and other conditions.

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, Computed Properties of 763120-58-7.

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

Wang, Peicheng published the artcileEffect of pyrazolium-derived compounds as templates in zeolite synthesis, Synthetic Route of 930-36-9, the publication is RSC Advances (2017), 7(38), 23272-23278, database is CAplus.

A series of diquaternary pyrazolium-derived organic templates (N,N’-dimethyl-N,N’-1,6-dihexylidenedipyrazolium, N,N’-diethyl-N,N’-1,6-dihexylidenedipyrazolium, N,N’-dipropyl-N,N’-1,6-dihexylidenedipyrazolium, denoted as 6C-DMP, 6C-DEP, 6C-DPP, resp.) with Me, Et and Pr groups substituted on the N atom of pyrazole ring at both terminals have been used in the synthesis of high silica MTW and MFI zeolites. Through combining the characterization results, including XRD, NMR, elemental anal., TG, XRF, FE-SEM, N₂ sorption and FE-TEM, with mol. mechanics simulations to explore the location, orientation and the interaction energies of the three templates, we confirmed the state of templates in zeolite framework, carefully characterized their morphol./structure properties, and finally investigated their different spatial effects for the zeolite formation. The study found that 6C-DMP and 6C-DEP are able to produce MTW, while 6C-DPP is able to produce MFI. 6C-DMP, owing to a good match with the MTW framework and can be used to synthesize regular MTW zeolite with few defects. The MTW zeolite prepared by using 6C-DEP as a template presents more defects and irregular macromorphol. due to a relatively poor match to the MTW framework. 6C-DPP can get MFI other than MTW due to a larger spatial hindrance, and it is located in the MFI framework with a special spatial orientation.

RSC Advances 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 C48H47FeP, Synthetic Route of 930-36-9.

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

Che, Bingchen published the artcileDynamic intracellular mechanical cues facilitate collective signaling responses, SDS of cas: 71203-35-5, the publication is iScience (2021), 24(5), 102396, database is CAplus and MEDLINE.

Collective behavior emerges in diverse life machineries, e.g., the immune responses to dynamic stimulations. The essential questions that arise here are that whether and how cells in vivo collectively respond to stimulation frequencies higher than their intrinsic natural values, e.g., the acute inflammation conditions. In this work, we systematically studied morphol. and signaling responses of population fibroblasts in an interconnected cell monolayer and uncovered that, besides the natural NF-κB oscillation frequency of 1/90 min-1, collective signaling response emerges in the cell monolayer at 1/20 min-1 TNF-α input periodicity as well. Using a customized microfluidic device, we independently induced dynamic chem. stimulation and cytoskeleton reorganization on the stand-alone cells to exclude the effect of cell-cell communication. Our results reveal that, at this particular frequency, chem. stimulation is translated into dynamic intracellular mech. cues through RAC1-medicated induction of dynamic cell-cell connections and cytoskeleton reorganizations, which synergize with chem. input to facilitate collective signaling responses.

iScience 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, SDS of cas: 71203-35-5.

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

Wu, Wenling published the artcileHierarchical architecture of two-dimensional Ti₃C₂ nanosheets@Metal-Organic framework derivatives as anode for hybrid li-ion capacitors, Application of 1-Methylpyrazole, the publication is Journal of Colloid and Interface Science (2022), 216-225, database is CAplus and MEDLINE.

Two-dimensional (2D) layered metal carbides materials called MXenes (e.g., Ti₃C₂) are significantly attentioned as electrode material for lithium-ion capacitors (LICs) because of its large surface-to-volume ratio and ultra-high electronic conductivity Whereas, as anode electrode material, the performance and application prospects of Ti₃C₂ are severely restricted to its lower theory. capacity. In this work, a straightforward and effective strategy to surmount the restrictions was developed to combine layered Ti₃C₂ nanosheets with dual Co/Zn metal-organic framework (MOF) polyhedrons derivatives through electrostatic assembly. Co₃O₄/ZnO polyhedrons could prevent the stacking of Ti₃C₂ nanosheets and provide prominent lithium storage capacity. Furthermore, the advanced structure of Ti₃C₂@Co₃O₄/ZnO as anode material could provide short Li⁺ paths, large electrolyte channels and excellent structural stability to enhance the electrochem. performance for LICs. As a result, the prepared Ti₃C₂@Co₃O₄/ZnO composite exhibited a specific capacity of 585.7 mAh/g at 0.1 A/g, and the electrode still delivered a capacity of 229 mAh/g at 2 A/g after 1000 cycles with 93% capacity retention in lithium-ion half cell. In addition, by assembling with activated carbon (AC) as cathode and Ti₃C₂@Co₃O₄/ZnO as anode, the LIC revealed an ultra-high energy d. of 196.8 Wh/kg at a power d. of 174.9 W/kg, and delivered a high energy output of 87.5 Wh/kg even at a power d. of 3500 W/kg. And its capacitance retention reaches 75% after 6000 cycles at 2 A/g. The advanced structure, handy preparation, and outstanding performance of layered carbon-based material Ti₃C₂@hollow polyhedrons composite might provide promising applications in LICs.

Journal of Colloid and Interface Science 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 C7H7ClN2S, Application of 1-Methylpyrazole.

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

Sun, Shaoyi published the artcileSystematic evaluation of amide bioisosteres leading to the discovery of novel and potent thiazolylimidazolidinone inhibitors of SCD1 for the treatment of metabolic diseases, Name: 1H-Pyrazole-4-boronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2014), 24(2), 520-525, database is CAplus and MEDLINE.

Several five- and six-membered heterocycles were introduced to replace the C2-position amide bond of the original 2-aminothiazole-based hit compound Specifically, replacement of the amide bond with an imidazolidinone moiety yielded a novel and potent thiazolylimidazolidinone series of SCD1 inhibitors. XEN723 I was identified after optimization of the thiazolylimidazolidinone series. This compound demonstrated a 560-fold improvement in in vitro potency and reduced plasma desaturation indexes in a dose dependent manner, with an EC₅₀ of 4.5 mg/kg.

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 C15H14Cl2S2, Name: 1H-Pyrazole-4-boronic acid.

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

Ma, Yuan published the artcileInsight on asym-Pyrazolium Ionic Liquids for Chemical Fixation of CO₂ and Propylene Epoxide into Propylene Carbonate without Organic Solvent and Metal, Related Products of pyrazoles-derivatives, the publication is Industrial & Engineering Chemistry Research (2018), 57(40), 13342-13352, database is CAplus.

From the perspective of environmental protection and resource utilization, the fixation of carbon dioxide (CO₂) is an interesting and meaningful topic. In this work, a series of asym-dialkylpyrazolium ionic liquids are synthesized by us to explore their catalytic activity for the cycloaddition of CO₂ and propylene epoxide to produce propylene carbonate (PC). They could be easily synthesized by a simple reaction, which is the premise for the large-scale application. The effect of alkyl chain length in cation on catalytic performance is investigated. Although asym-pyrazolium ILs present less catalytic activity than sym-pyrazolium ILs, the product yield catalyzed by EPPzBr is as high as 85% with PC selectivity of 99%, which is better than most of nonfunctionalized ionic liquids Moreover, the catalyst could be reused at least five times without significant loss of catalytic activity. To elucidate the structure-property relationship, the difference between asym-pyrazolium ILs and sym-pyrazolium ILs is discussed in detail by the Double-IL model associated with the noncovalent interactions and atoms in mol. anal. The kind of single-component catalysts for the fixation of CO₂ is further enriched.

Industrial & Engineering Chemistry Research 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, Related Products of pyrazoles-derivatives.

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

Yang, Fan published the artcileHomology modelling of G-coupled protein receptor 109A and docking simulation with pyrazole agonists, Quality Control of 890590-91-7, the publication is Jisuanji Yu Yingyong Huaxue (2016), 33(5), 569-574, database is CAplus.

Niacin receptor G-coupled protein receptor 109A (GPR109A) is an important target protein of the treatment of cardiovascular diseases and disorders of lipid metabolism diseases. Since GPR109A is one membrane protein, the crystal structure of which has not been resolved, there are many challenges to drug design for the receptor. Based on the mouse PUMA-G crystal structure, the three-dimensional structure of GPR109A was built by using the homol. modeling method. The model was evaluated by using the Ramachandran Plot and Profile-3D, and the model was optimized with MMFF94 force field, membrane and method of loop, and finally one stabile model was obtained and 12 sites that might be the active sites in the optimal model were found. SYBYL-X2 software was used to build GPR109A pyrazole agonist drug mols., through the steepest descent method and the Conjugate gradient method to receive the most stable conformation of the small drugs mols. All the agonists were docked into each active site of the protein by Libdock method, receiving the interaction models. We analyzed the distribution of amino acid of each active site, and took 5-methyl-3-carboxylic acid as a reference drug mol. to explore the interaction force with each protein active site. This study has theor. significance in designing G-coupled protein receptor 109A pyrazole agonists.

Jisuanji Yu Yingyong Huaxue published new progress about 890590-91-7. 890590-91-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Carboxylic acid, name is 3-Isopropyl-1H-pyrazole-5-carboxylic acid, and the molecular formula is C3H5BN2O2, Quality Control of 890590-91-7.

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

Yang, Mengchen published the artcileHighly enantioselective Michael addition of pyrazolin-5-ones to nitroolefins catalyzed by cinchona alkaloid derived 4-methylbenzoylthioureas, SDS of cas: 14580-22-4, the publication is Chirality (2018), 30(9), 1096-1104, database is CAplus and MEDLINE.

Cinchona alkaloid-derived (4-methyl/nitro)benzoylthioureas were synthesized, which smoothly catalyzed the asym. Michael addition of pyrazolin-5-ones to nitroolefins. The results showed that electronic effects of substituents in the benzene ring of benzoylthioureas have subtle influences on their catalytic abilities and electron donating Me group was favored than electron withdrawing nitro group. Preliminary Hartree-Fock calculations revealed that in the catalytic cycle, hydrogen bond energies of the complex formed with 4-methylbenzoylthioureas were about 0.19 to 1.56 kcal/mol higher than with the corresponding 4-nitrobenzoylthioureas. 4-Methylbenzoylthioureas were identified as the most effective catalysts that promoted asym. Michael addition of pyrazolin-5-ones to nitroolefins to give the S- or R-products with high enantioselectivities.

Chirality 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 C4H10BBrO2, SDS of cas: 14580-22-4.

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

Wang, Zhen published the artcileDiscovery of 2-(3-(3-Carbamoylpiperidin-1-yl)phenoxy)acetic Acid Derivatives as Novel Small-Molecule Inhibitors of the β-Catenin/B-Cell Lymphoma 9 Protein-Protein Interaction, Product Details of C3H5BN2O2, the publication is Journal of Medicinal Chemistry (2021), 64(9), 5886-5904, database is CAplus and MEDLINE.

The β-catenin/B-cell lymphoma 9 (BCL9) protein-protein interaction (PPI) is a potential target for the suppression of hyperactive Wnt/β-catenin signaling that is vigorously involved in cancer initiation and development. Herein, we describe the medicinal chem. optimization of a screening hit to yield novel small-mol. inhibitors of the β-catenin/BCL9 interaction. The best compound 30 can disrupt the β-catenin/BCL9 interaction with a K_i of 3.6μM in AlphaScreen competitive inhibition assays. Cell-based experiments revealed that 30 selectively disrupted the β-catenin/BCL9 PPI, while leaving the β-catenin/E-cadherin PPI unaffected, dose-dependently suppressed Wnt signaling transactivation, downregulated oncogenic Wnt target gene expression, and on-target selectively inhibited the growth of cancer cells harboring aberrant Wnt signaling. This compound with a new chemotype can serve as a lead compound for further optimization of inhibitors for β-catenin/BCL9 PPI.

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 C4H6BrFO2, Product Details of C3H5BN2O2.

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