pyrazoles-derivatives

Kurasawa, Osamu published the artcileIdentification of a new class of potent Cdc7 inhibitors designed by putative pharmacophore model: Synthesis and biological evaluation of 2,3-dihydrothieno[3,2-d]pyrimidin-4(1H)-ones, Quality Control of 1009071-34-4, the publication is Bioorganic & Medicinal Chemistry (2017), 25(7), 2133-2147, database is CAplus and MEDLINE.

Cell division cycle 7 (Cdc7) is a serine/threonine kinase that plays important roles in the regulation of DNA replication process. A genetic study indicates that Cdc7 inhibition can induce selective tumor-cell death in a p53-dependent manner, suggesting that Cdc7 is an attractive target for the treatment of cancers. In order to identify a new class of potent Cdc7 inhibitors, we generated a putative pharmacophore model based on in silico docking anal. of a known inhibitor with Cdc7 homol. model. The pharmacophore model provided a min. structural motif of Cdc7 inhibitor, by which preliminary medicinal chem. efforts identified a dihydrothieno[3,2-d]-pyrimidin-4(1H)-one scaffold having a heteroaromatic hinge-binding moiety. The structure-activity relationship (SAR) studies resulted in the discovery of new, potent, and selective Cdc7 inhibitors 14a, c, e. Furthermore, the high selectivity of 14c, e for Cdc7 over Rho-associated protein kinase 1 (ROCK1) is discussed by utilizing a docking study with Cdc7 and ROCK2 crystal structures.

Bioorganic & Medicinal Chemistry published new progress about 1009071-34-4. 1009071-34-4 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Amide,Boronate Esters,Boronic Acids,Boronic acid and ester, name is tert-Butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate, and the molecular formula is C15H25BN2O4, Quality Control of 1009071-34-4.

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

Kublicki, Marcin published the artcile1,4-Phenylenebis((1-methyl-1H-pyrazol-5-yl)borinic 8-oxyquinolinate) as a photoredox catalyst in the atom transfer radical addition of iodoperfluoroalkanes to alkenyl groups bearing organoboron compounds, Category: pyrazoles-derivatives, the publication is Tetrahedron Letters (2019), 60(29), 1918-1923, database is CAplus.

The key photocatalytic properties of a transition-metal-free heteroleptic complex I (1) derived from 1,4-phenyldiboronic acid were evaluated. This compound was utilized in the atom transfer radical addition of iodoperfluoroalkanes C_nF_2n+1I (n = 1-4) to a series of allylic arylboronate compounds CH₂:CHCH₂XAr[B] [X = bond, O, CH₂; Ar = phenylene, thiophenediyl; [B] = B(OH)₂, BF₃K] to give C-I activation products, [B]ArXCH₂CHICH₂C_nF_2n+1 (2–14). The products of these reactions retained the B-C bond, and Suzuki-Miyaura coupling of one product gave biphenyl derivatives The X-ray anal. of one of the obtained perfluoroalkylated boronic acids revealed the presence of open star-shaped channels.

Tetrahedron 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, Category: pyrazoles-derivatives.

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

Hong, Fang-Tsao published the artcileSmall Molecule Disruptors of the Glucokinase-Glucokinase Regulatory Protein Interaction: 4. Exploration of a Novel Binding Pocket, HPLC of Formula: 724710-02-5, the publication is Journal of Medicinal Chemistry (2014), 57(14), 5949-5964, database is CAplus and MEDLINE.

Structure-activity relationship investigations conducted at the 5-position of the N-pyridine ring of a series of N-arylsulfonyl-N’-2-pyridinyl-piperazines led to the identification of a novel bis-pyridinyl piperazine sulfonamide I that was a potent disruptor of the glucokinase-glucokinase regulatory protein (GK-GKRP) interaction. Anal. of the x-ray cocrystal of compound I bound to hGKRP revealed that the 3-pyridine ring moiety occupied a previously unexplored binding pocket within the protein. Key features of this new binding mode included forming favorable contacts with the top face of the Ala27-Val28-Pro29 (“shelf region”) as well as an edge-to-face interaction with the Tyr24 side chain. Compound I was potent in both biochem. and cellular assays (IC₅₀ = 0.005 μM and EC₅₀ = 0.205 μM, resp.) and exhibited acceptable pharmacokinetic properties for in vivo evaluation. When administered to db/db mice (100 mg/kg, po), compound I demonstrated a robust pharmacodynamic effect and significantly reduced blood glucose levels up to 6 h postdose.

Journal of Medicinal 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 C3H5BN2O2, HPLC of Formula: 724710-02-5.

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

Bercean, Vasile-Nicolae published the artcileAzo compounds derived from 1H-5-amino-4-ethoxycarbonyl-3-methyl-pyrazole and phenols or phenolic derivatives and possibilities of their cyclization to pyrazolo[5,1-c]benzo[1,2-e][1,2,4]triazines, Computed Properties of 23286-70-6, the publication is Revista de Chimie (Bucharest, Romania) (2011), 62(2), 154-157, database is CAplus.

The coupling reaction of 1H-4-ethoxycarbonyl-3-methylpyrazol-5-yldiazonium chloride with phenols and phenolic derivatives led to 1H-5-arylazo-4-ethoxycarbonyl-3-methylpyrazoles. Cyclization of one of the latter compounds, [1H-4-ethoxycarbonyl-5-(4,6-dimethoxy-2-hydroxyphenylazo)-3-methylpyrazole] gave the corresponding pyrazolo[5,1-c]benzo[1,2-e][1,2,4]triazine.

Revista de Chimie (Bucharest, Romania) published new progress about 23286-70-6. 23286-70-6 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Amine,Ester, name is Ethyl 5-amino-3-methyl-1H-pyrazole-4-carboxylate, and the molecular formula is C7H11N3O2, Computed Properties of 23286-70-6.

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

Bercean, Vasile-Nicolae published the artcileNew azo compounds derived from 1H-5-amino-4-ethoxycarbonyl-3-methyl-pyrazole and 3-mono- or 1,3-disubstituted pyrazol-5-ones, Synthetic Route of 23286-70-6, the publication is Revista de Chimie (Bucharest, Romania) (2010), 61(4), 364-367, database is CAplus.

Pyrazole-derived azo compounds were designed, and the synthesis of the target compounds was achieved by a coupling reaction of 3-amino-5-methyl-1H-pyrazole-4-carboxylic acid Et ester (I) with pyrazolone derivatives The products thus obtained were confirmed by MS, IR, UV-VIS, ¹H-NMR, and ¹³C-NMR, and existed in multiple tautomeric forms.

Revista de Chimie (Bucharest, Romania) published new progress about 23286-70-6. 23286-70-6 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Amine,Ester, name is Ethyl 5-amino-3-methyl-1H-pyrazole-4-carboxylate, and the molecular formula is C7H11N3O2, Synthetic Route of 23286-70-6.

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

Zhang, Lingtian published the artcileDiscovery of N-Trisubstituted Pyrimidine Derivatives as Type I RET and RET Gatekeeper Mutant Inhibitors with a Novel Kinase Binding Pose, Name: 1-Methylpyrazole, the publication is Journal of Medicinal Chemistry (2022), 65(2), 1536-1551, database is CAplus and MEDLINE.

Mutations of the rearranged during transfection (RET) kinase are frequently reported in cancer, which make it as an attractive therapeutic target. Herein, we discovered a series of N-trisubstituted pyrimidine derivatives as potent inhibitors for both wild-type (weight) RET and RET^V804M, which is a resistant mutant for several FDA-approved inhibitors. The X-ray structure of a representative inhibitor with RET revealed that the compound binds in a unique pose that bifurcates beneath the P-loop and confirmed the compound as a type I inhibitor. Through the structure-activity relationship (SAR) study, compound 20 (I) was identified as a lead compound, showing potent inhibition of both RET and RET^V804M. Addnl., compound 20 displayed potent antiproliferative activity of CCDC6-RET-driven LC-2/ad cells. Anal. of RET phosphorylation indicated that biol. activity was mediated by RET inhibition. Collectively, N-trisubstituted pyrimidine derivatives could serve as scaffolds for the discovery and development of potent inhibitors of type I RET and its gatekeeper mutant for the treatment of RET-driven cancers.

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 C9H6N2O2, Name: 1-Methylpyrazole.

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

Li, Yun published the artcileA Metal-Ligand Layer Compatible with Various Types of Pillars for New Porous Coordination Polymers, Computed Properties of 19959-71-8, the publication is Crystal Growth & Design (2020), 20(10), 7021-7026, database is CAplus.

Pillared-layer structures are classic for porous coordination polymers (PCPs), but suitable metal-ligand layers for such structures are rare. Here, the authors report a cationic {Zn₂(pzdc)}⁺ (H₃pzdc = 3,5-pyrazoledicarboxylic acid) layer compatible with various types of pillar ligands. Solvothermal reactions of Zn(NO₃)₂·6H₂O and H₃pzdc with 4-(pyridin-4-yl)-1H-pyrazole (Hpypz), 1,4-benzenedicarboxylic acid (H₂bdc), or 2-amino-1,4-benzenedicarboxylic acid (H₂abdc) in a mixed solvent of H₂O and N,N-dimethylformamide (DMF) produced three pillared-layer PCPs, namely [Zn₄(pzdc)₂(pypz)₂]·guest (1), [Zn₄(pzdc)₂(bdc)(H₂O)_1.53(DMF)_0.47]·guest (2), and [Zn₄(pzdc)₂(abdc)(H₂O)_1.52(DMF)_0.48]·guest (3), resp. Single-crystal X-ray analyses revealed that the {Zn₂(pzdc)}⁺ layers are fully pillared by pypz^– in 1 and half pillared by bdc^2- and abdc^2- in 2 and 3, because the anionic pillars possess different charges. Consequently, 1 shows one-dimensional (1D) channels with a small porosity and 2 and 3 show 2D channels with large porosities, both of which were verified by N₂ and CO₂ adsorption isotherms. While 1 has no coordinated solvent mols. and exhibits a high water stability, 2 and 3 possess coordinated solvent mols. and quickly transform to crystals of 2D coordination networks in water, [Zn₄(pzdc)₂(OH)₂(H₂O)₆]·H₂bdc·4H₂O (4) and [Zn₄(pzdc)₂(H₂abdc)(OH)₂(H₂O)₅]·2H₂O (5), resp., which can be further exfoliated into ultrathin nanosheets in an ammonia solution A new metal-ligand layer can adopt various types of pillars to give a series of pillared-layer PCPs with tunable pillar densities, porosities, and water stabilities. The water-instable ones can be exfoliated to ultrathin nanosheets with intermediates suitable for single-crystal diffraction characterization.

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, Computed Properties of 19959-71-8.

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

Kamasaki, Tomoko published the artcileFBP17-mediated finger-like membrane protrusions in cell competition between normal and RasV12-transformed cells, Recommanded Product: 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, the publication is iScience (2021), 24(9), 102994, database is CAplus and MEDLINE.

At the initial stage of carcinogenesis, cell competition often occurs between newly emerging transformed cells and the neighboring normal cells, leading to the elimination of transformed cells from the epithelial layer. For instance, when RasV12-transformed cells are surrounded by normal cells, RasV12 cells are apically extruded from the epithelium. However, the underlying mechanisms of this tumor-suppressive process still remain enigmatic. We first show by electron microscopic anal. that characteristic finger-like membrane protrusions are projected from both normal and RasV12 cells at their interface. In addition, FBP17, a member of the F-BAR proteins, accumulates in RasV12 cells, as well as surrounding normal cells, which plays a pos. role in the formation of finger-like protrusions and apical elimination of RasV12 cells. Furthermore, cdc42 acts upstream of these processes. These results suggest that the cdc42/FBP17 pathway is a crucial trigger of cell competition, inducing “protrusion to protrusion response” between normal and RasV12-transformed cells.

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, 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

Ariyani, Winda published the artcileGadolinium-based contrast agent accelerates the migration of astrocyte via integrin αvβ3 signaling pathway, Quality Control of 71203-35-5, the publication is Scientific Reports (2022), 12(1), 5850, database is CAplus and MEDLINE.

Gadolinium (Gd)-based contrast agents (GBCAs) are chems. injected i.v. during magnetic resonance imaging to enhance the diagnostic yield. Repeated use of GBCAs causes their deposition in the brain. Such deposition may affect various neuronal cells, including astrocytes. In this study, we examined the effect of GBCAs (Omniscan, Magnescope, Magnevist, and Gadovist) on astrocyte migration, which is critical for formation of neurons during development and maintaining brain homeostasis. All GBCAs increased cell migration and adhesion with increased actin remodelling. Knockdown of integrin αvβ3 by RNAi or exposure to integrin αvβ3 inhibitor reduced astrocyte migration. GBCAs increased phosphorylation of downstream factors of αvβ3, such as FAK, ERK1/2, and Akt. The phosphorylation of all these factors were reduced by RNAi or integrin αvβ3 inhibitor. GBCAs also increased the phosphorylation of their downstream factor, Rac1/cdc42, belonging to the RhoGTPases family. Coexposure to the selective RhoGTPases inhibitors, decreased the effects of GBCAs on cell migration. These findings indicate that GBCAs exert their action via integrin αvβ3 to activate the signaling pathway, resulting in increased astrocyte migration. Thus, the findings of the study suggest that it is important to avoid the repeated use of GBCAs to prevent adverse side effects in the brain, particularly during development.

Scientific 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, Quality Control of 71203-35-5.

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

Kurasawa, Osamu published the artcileDiscovery of a Novel, Highly Potent, and Selective Thieno[3,2-d]pyrimidinone-Based Cdc7 Inhibitor with a Quinuclidine Moiety (TAK-931) as an Orally Active Investigational Antitumor Agent, Safety of tert-Butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate, the publication is Journal of Medicinal Chemistry (2020), 63(3), 1084-1104, database is CAplus and MEDLINE.

In our pursuit of developing a novel, potent, and selective cell division cycle 7 (Cdc7) inhibitor, we optimized the previously reported thieno[3,2-d]pyrimidinone analog I showing time-dependent Cdc7 kinase inhibition and slow dissociation kinetics. These medicinal chem. efforts led to the identification of compound 3d, which exhibited potent cellular activity, excellent kinase selectivity, and antitumor efficacy in a COLO205 xenograft mouse model. However, the issue of formaldehyde adduct formation emerged during a detailed study of 3d, which was deemed an obstacle to further development. A structure-based approach to circumvent the adduct formation culminated in the discovery of compound 11b (TAK-931) possessing a quinuclidine moiety as a preclin. candidate. In this paper, the design, synthesis, and biol. evaluation of this series of compounds will be presented.

Journal of Medicinal Chemistry published new progress about 1009071-34-4. 1009071-34-4 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Amide,Boronate Esters,Boronic Acids,Boronic acid and ester, name is tert-Butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate, and the molecular formula is C15H25BN2O4, Safety of tert-Butyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate.

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