pyrazoles-derivatives

Rong, Deqin published the artcileStructure-Aided Design, Synthesis, and Biological Evaluation of Potent and Selective Non-Nucleoside Inhibitors Targeting Protein Arginine Methyltransferase 5, Application In Synthesis of 930-36-9, the publication is Journal of Medicinal Chemistry (2022), 65(11), 7854-7875, database is CAplus and MEDLINE.

PRMT5 is a major type II protein arginine methyltransferase and plays important roles in diverse cellular processes. Overexpression of PRMT5 is implicated in various types of cancer. Many efforts have been made to develop potent and selective PRMT5 inhibitors, the most potent of which is usually derived from nucleoside structures. Here, we designed a novel series of non-nucleoside PRMT5 inhibitors through the structure-aided drug design approach. SAR exploration and metabolic stability optimization led to the discovery of compound 41 as a potent PRMT5 inhibitor with good selectivity. Addnl., compound 41 exerted antiproliferative effects against A375 cells by inducing apoptosis and potently inhibited the methyltransferase activity of PRMT5 in cells. Moreover, it showed attractive pharmacokinetic properties and markedly suppressed the tumor growth in an A375 tumor xenograft model. These results clearly indicate that 41 is a highly potent and selective non-nucleoside PRMT5 inhibitor.

Journal of Medicinal Chemistry 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, Application In Synthesis of 930-36-9.

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

Bie, Hong-Yan published the artcileCrystal structure of (4Z)-4-((2-(methylamino)phenylamino)(phenyl)methylene)- 3-methyl-1-phenyl-1H-pyrazol-5-(4H)-one, C₂₄H₂₂N₄O, Application In Synthesis of 4551-69-3, the publication is Zeitschrift fuer Kristallographie – New Crystal Structures (2014), 229(1), 17-18, database is CAplus.

The crystal structure of the title compound is herein given. The title compound was synthesized from of 1-phenyl-3-methyl-4-benzoyl-5-pyrazolone and N-methylbenzene-1,2-diamine. The Schiff base has a Z configuration about the double bound and shows hydrogen bonding.

Zeitschrift fuer Kristallographie – New Crystal Structures 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, Application In Synthesis of 4551-69-3.

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

Mo, Zong-Wen published the artcileTuning Connectivity and Flexibility of Two Zinc-Triazolate-Carboxylate Type Porous Coordination Polymers, Recommanded Product: 4-(1H-Pyrazol-4-yl)pyridine, the publication is Crystal Growth & Design (2018), 18(5), 2694-2698, database is CAplus.

Solvothermal reactions of Zn(II) salts and 4-(1H-pyrazol-4-yl)pyridine (Hpypz) in the presence of monocarboxylate or dicarboxylate ligands produced two porous coordination polymers, namely, [Zn(pypz)(OAc)]·guest (1·g, HOAc = acetic acid) and [Zn₂(pypz)₂(oba)]·guest (2·g, H₂oba = 4,4′-oxobisbenzoic acid). Single-crystal x-ray diffraction analyses showed that both 1 and 2 contain 2-fold interpenetrated three-dimensional nbo-a {Zn(pypz)}⁺ networks consisting of 3-connected Zn(II) ions and 3-connected pypz^– ligands. After the carboxylate ligands were considered, 1 retains the nbo-a network structure and contains one-dimensional channels with very narrow apertures. However, 2 becomes a new uninodal 6-connected topol. (point symbol 3³.4².5⁶.6⁴) and contains discrete pores. Powder x-ray diffraction showed that, after solvent removal, 1 undergoes obvious framework shrinkage, while 2 retains the original unit cell. Activated 1 and 2 both exclude N₂ at 77 K, but readily adsorb CO₂ at 195 K with unconventional isotherm shapes, indicating the different types of framework flexibilities.

Crystal Growth & Design 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

Jayabal, Panneerselvam published the artcileNELL2-cdc42 signaling regulates BAF complexes and Ewing sarcoma cell growth, Synthetic Route of 71203-35-5, the publication is Cell Reports (2021), 36(1), 109254, database is CAplus and MEDLINE.

BAF chromatin remodeling complexes play important roles in chromatin regulation and cancer. Here, we report that Ewing sarcoma cells are dependent on the autocrine signaling mediated by NELL2, a secreted glycoprotein that has been characterized as an axon guidance mol. NELL2 uses Robo3 as the receptor to transmit critical growth signaling. NELL2 signaling inhibits cdc42 and upregulates BAF complexes and EWS-FLI1 transcriptional output. We demonstrate that cdc42 is a neg. regulator of BAF complexes, inducing actin polymerization and complex disassembly. Furthermore, we identify NELL2highCD133highEWS-FLI1 high and NELL2low CD133low EWS-FLI1low populations in Ewing sarcoma, which display phenotypes consistent with high and low NELL2 signaling, resp. We show that NELL2, CD133, and EWS-FLI1 pos. regulate each other and upregulate BAF complexes and cell proliferation in Ewing sarcoma. These results reveal a signaling pathway regulating critical chromatin remodeling complexes and cancer cell proliferation.

Cell Reports 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, Synthetic Route of 71203-35-5.

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

Yang, Yong published the artcileImpact of Boronate Capping Groups on Biological Characteristics of Novel ^99mTc(III) Complexes [^99mTcCl(CDO)(CDOH)₂B-R] (CDOH₂ = Cyclohexanedione Dioxime), Recommanded Product: (1H-Pyrazol-5-yl)boronic acid, the publication is Bioconjugate Chemistry (2015), 26(2), 316-328, database is CAplus and MEDLINE.

This study sought to explore the impact of boronate groups on the heart uptake and myocardial retention of novel ^99mTc(III) complexes [^99mTcCl(CDO)(CDOH)₂B-R] (^99mTc-ISboroxime: R = isoxazol-4-yl (IS); ^99mTc-MPboroxime: R = N-methylpyridinium (MP); ^99mTc-PAboroxime: R = pyrazol-3-yl (PA); ^99mTc-PYboroxime: R = pyridin-3-yl (PY); and ^99mTc-5Uboroxime: R = uracil-5-yl (5U)). All five new ^99mTc(III) radiotracers were prepared in high yield and high radiochem. purity (RCP = 90-98%), and they remained stable in the kit mixture for >6 h. Biodistribution and imaging (planar and SPECT) studies were carried out using Sprague-Dawley (SD) rats. Planar image quantification was performed to compare their myocardial retention and liver clearance kinetics. It was found that their heart retention and liver clearance curves were best fitted to the biexponential decay function. The initial heart uptake at 0-1 min after injection followed the general ranking order of ^99mTc-ISboroxime (4.98 ± 1.05%ID) ∼ ^99mTc-Teboroxime (4.56 ± 0.91%ID) ∼ ^99mTc-PAboroxime (4.03 ± 1.23%ID) ∼ ^99mTc-PYboroxime (4.07 ± 0.80%ID) > ^99mTc-5Uboroxime (3.24 ± 0.67%ID) > ^99mTc-MPboroxime (2.53 ± 0.65%ID). The fast-phase myocardial retention time followed the general order of ^99mTc-PAboroxime (3.21 ± 0.29 min) > ^99mTc-Teboroxime (1.63 ± 0.40 min) ∼ ^99mTc-PYboroxime (1.57 ± 0.29 min) ∼ ^99mTc-ISboroxime (1.55 ± 0.32 min) > ^99mTc-MPboroxime (0.68 ± 0.16 min) > ^99mTc-5Uboroxime (0.33 ± 0.11 min). ^99mTc-PAboroxime (3.05 ± 1.10%ID/g) and ^99mTc-ISboroxime (3.75 ± 0.68%ID/g) had the 2 min initial heart uptake very close to that of ^99mTc-Teboroxime (3.30 ± 0.50%ID/g). However, the myocardial retention time of ^99mTc-PAboroxime was significantly longer than that of ^99mTc-ISboroxime and ^99mTc-Teboroxime. Even though the best time window is 0-5 min for SPECT image acquisition, high quality SPECT images could be obtained during the first 30 min postinjection of ^99mTc-PAboroxime in SD rats. This statement was supported by the SPECT/CT studies in normal pigs. On the basis of results from this study, it was concluded that boronate groups had significant impact on the heart uptake, myocardial retention, and liver clearance kinetics of ^99mTc(III) complexes [^99mTcCl(CDO)(CDOH)₂B-R]. The combination of high initial heart uptake with longer myocardial retention makes it possible to image the heart with ^99mTc-PAboroxime during the first 30 min using both standard and specialized cardiac SPECT cameras.

Bioconjugate Chemistry 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 C7H3IN2O2, Recommanded Product: (1H-Pyrazol-5-yl)boronic acid.

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

Lv, Xunlei published the artcileAssignment of NMR data and Conformational analysis of larotrectinib and its precursors, Related Products of pyrazoles-derivatives, the publication is Tetrahedron (2021), 132064, database is CAplus.

NMR experiments were used to identify the two main conformations of Larotrectinib and its synthetic precursor, the nitro compound 4. Conformational anal. by dynamic NMR was performed in different temperature and solvents, combining 2D EXSY and NOE experiments The results revealed the conformations of Larotrectinib and compound 4 were caused by the barrier to rotation of C11-N17. Meanwhile, the conformational specific structures of compound 4 were postulated based on NOE data and mol. simulation. The complete assignments of ¹H and ¹³C NMR data for compounds 1, 4 and 5 were reported for the first time.

Tetrahedron published new progress about 1363380-51-1. 1363380-51-1 belongs to pyrazoles-derivatives, auxiliary class Other Aromatic Heterocyclic,Chloride,Nitro Compound, name is 5-Chloro-3-nitropyrazolo[1,5-a]pyrimidine, and the molecular formula is C6H3ClN4O2, Related Products of pyrazoles-derivatives.

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

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