Day: November 29, 2022

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

Ozaki, Toyoko published the artcileSolvent extraction of zinc with 1-(2′-chlorophenyl)-3-methyl-4-aroyl-5-pyrazolones, Safety of 1-(2-Chlorophenyl)-3-methyl-5-pyrazolone, the publication is Analytica Chimica Acta (1989), 226(1), 187-92, database is CAplus.

1-(2′-Chlorophenyl)-3-methyl-4-aroyl-5-pyrazolone derivatives were synthesized and steric effects of the 2-chlorophenyl group on the acid dissociation constants and the solvent extraction reaction of Zn were studied. Steric effects on the synergic extraction of Zn with trioctylphosphine oxide were also examined

Analytica Chimica Acta 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 C10H9ClN2O, Safety of 1-(2-Chlorophenyl)-3-methyl-5-pyrazolone.

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

Maurya, R. C. published the artcilePreparation and characterization of some novel cyanonitrosyl {CrNO}⁵ complexes of chromium involving biologically important 2-pyrazoline-5-one derivatives, Recommanded Product: 1-(2-Chlorophenyl)-3-methyl-5-pyrazolone, the publication is National Academy Science Letters (India) (1992), 15(9), 299-301, database is CAplus.

[Cr(NO)(CN)₂(L)₂(H₂O)] (L = 1-(2′-chlorophenyl)-, 1-(4′-tolyl)-, or 1-(4′-nitrophenyl)-, and 1-(4′-sulfophenyl)-3-methyl-2-pyrazolin-5-one) were isolated as solids by the interaction of K₃[Cr(NO)(CN)₅].H₂O with L. The complexes, which were characterized by elemental anal., magnetic measurements, molar conductances, TGA, ESR and IR spectral studies, contain chromium(I) in a low-spin d⁵-configuration. An octahedral structure is proposed for the complexes.

National Academy Science Letters (India) 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 C10H9ClN2O, Recommanded Product: 1-(2-Chlorophenyl)-3-methyl-5-pyrazolone.

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

London, Nir published the artcileCovalent docking of large libraries for the discovery of chemical probes, SDS of cas: 1072945-88-0, the publication is Nature Chemical Biology (2014), 10(12), 1066-1072, database is CAplus and MEDLINE.

Chem. probes that form a covalent bond with a protein target often show enhanced selectivity, potency and utility for biol. studies. Despite these advantages, protein-reactive compounds are usually avoided in high-throughput screening campaigns. Here we describe a general method (DOCKovalent) for screening large virtual libraries of electrophilic small mols. We apply this method prospectively to discover reversible covalent fragments that target distinct protein nucleophiles, including the catalytic serine of AmpC β-lactamase and noncatalytic cysteines in RSK2, MSK1 and JAK3 kinases. We identify submicromolar to low-nanomolar hits with high ligand efficiency, cellular activity and selectivity, including what are to our knowledge the first reported reversible covalent inhibitors of JAK3. Crystal structures of inhibitor complexes with AmpC and RSK2 confirm the docking predictions and guide further optimization. As covalent virtual screening may have broad utility for the rapid discovery of chem. probes, we have made the method freely available through an automated web server (http://covalent.docking.org/).

Nature Chemical Biology 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, SDS of cas: 1072945-88-0.

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

De Pascali, Sandra A. published the artcileSynthesis, Crystal Structure, and Biological Study of Pt^II Complexes with 4-Acyl-5-pyrazolones, Product Details of C17H14N2O2, the publication is European Journal of Inorganic Chemistry (2014), 2014(7), 1249-1259, database is CAplus.

The syntheses of new Pt^II complexes with 4-acyl-5-pyrazolones [HQ^Ph = 1-phenyl-3-methyl-4-benzoylpyrazol-5-one, a; HQ^py,CF3 = 1-(2-pyridyl)-3-methyl-trifluoroacetylpyrazol-5-one, b] are reported: trans-[PtCl₂(DMSO)(HQ^Ph)] (1a), cis-[PtCl₂(DMSO)(HQ^Ph)] (2a), [PtCl(DMSO)(Q^py,CF3)] (1b), and [PtCl₂(KQ^py,CF3)] (2b). All complexes were characterized by multinuclear (¹H, ¹³C, ¹⁹F, and ¹⁹⁵Pt), multidimensional NMR spectroscopy and single-crystal x-ray diffraction analyses. The isomer trans-[PtCl₂(DMSO)(HQ^Ph)] (1a) crystallizes in two polymorphic forms, which correspond to two different conformers. In the trans-syn conformer (1a_M) (monoclinic, space group P2₁/c), the H atom of the enol group [O(1)H(1)] establishes an intramol. hydrogen bond with the ketone oxygen (O2), whereas in the trans-anti conformer (1a_O) (orthorhombic, space group Pca2₁), the same groups are involved in an analogous intermol. H bond. Interestingly, the cis isomer (2a) showed in solution and at room temperature slow rotation around both the Pt-N1 and the Pt-S bonds, which restrained both the acylpyrazolone and DMSO ligand motion. Moreover, the water solubility of the complexes trans- and cis-[PtCl₂(DMSO)(HQ^Ph)] (1a and 2a) and [PtCl₂(KQ^py,CF3)] (2b) allowed to perform in vitro biol. assays on platinum-sensitive human endometrium (HeLa) and platinum-resistant human breast (MCF-7) cancer cell lines. It was also possible to compare their cytotoxicity to cisplatin. Interestingly, trans isomer 1a showed higher cytotoxicity on HeLa cells compared to the cis isomer 2a.

European Journal of Inorganic 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, Product Details of C17H14N2O2.

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

Zhang, Xin-Ke published the artcileIodine-catalyzed oxidative annulation: facile synthesis of pyrazolooxepinopyrazolones via methyl azaarene sp³ C-H functionalization, Synthetic Route of 14580-22-4, the publication is Organic & Biomolecular Chemistry (2022), 20(6), 1236-1242, database is CAplus and MEDLINE.

An iodine-catalyzed Me azaarene sp³ C-H functionalization has been developed for the synthesis of a seven-membered O-heterocyclic architecture containing three different heterocyclic aromatic hydrocarbons. This method can be applied to a wide range of substituted Me azaarenes and diverse 2,4-dihydro-3H-pyrazol-3-ones, and brings about the efficient preparation of 2,9-dihydrooxepino[2,3-c:6,5-c’]dipyrazol-3(7H)-ones in high yields with the merits of low catalyst loading, good functional group tolerance and metal-free conditions.

Organic & Biomolecular 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 C7H10BNO3, Synthetic Route of 14580-22-4.

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