Day: November 28, 2022

Hoeppner, F. D. published the artcileMO calculations on photographic development. IX. Experimental and quantum chemical investigations on the acidity of 5-pyrazolones, Computed Properties of 14580-22-4, the publication is Journal fuer Praktische Chemie (Leipzig) (1976), 318(4), 555-64, database is CAplus.

The pKs values of 49 derivatives of 5-pyrazolone were measured by potentiometric titration and their 1H-NMR spectra were recorded in Me2SO-d6. The exptl. acidity order correlates with both Hammett substitution constants and HMO electron densities.

Journal fuer Praktische Chemie (Leipzig) 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, Computed Properties of 14580-22-4.

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

Nam, Mina published the artcileDiscovery and biological evaluation of tetrahydrothieno[2,3-c]pyridine derivatives as selective metabotropic glutamate receptor 1 antagonists for the potential treatment of neuropathic pain, Application of 3-Isopropyl-1H-pyrazole-5-carboxylic acid, the publication is European Journal of Medicinal Chemistry (2015), 245-258, database is CAplus and MEDLINE.

Metabotropic glutamate receptor 1 (mGluR1) was a prime target for drug discovery due to its heavy involvement in various brain disorders. Recent studies suggested that mGluR1 is associated with chronic pain and can serve as a promising target for the treatment of neuropathic pain. In an effort to develop a novel mGluR1 antagonist, the authors designed and synthesized a library of compounds with tetrahydrothieno[2,3-c]pyridine scaffold. Among these compounds, compound 2-(Benzylamino)-6-(3-methyl-1H-pyrazole-5-carbonyl)4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carbonitrile and 2-(Benzylamino)-6-(4-fluorobenzoyl)-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carbonitrile showed excellent antagonistic activity in vitro and demonstrated pain-suppressing activity in animal models of pain. Both compounds were orally active, and compound 2-(Benzylamino)-6-(3-methyl-1H-pyrazole-5-carbonyl)4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carbonitrile exhibited a favorable pharmacokinetic profile in rats. The authors believe that these compounds can provide a promising lead compound that is suitable for the potential treatment of neuropathic pain.

European Journal of Medicinal Chemistry 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 C7H10N2O2, Application of 3-Isopropyl-1H-pyrazole-5-carboxylic acid.

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

Yoon, Suyoung published the artcileStructure-activity relationship of leucyladenylate sulfamate analogues as leucyl-tRNA synthetase (LRS)-targeting inhibitors of Mammalian target of rapamycin complex 1 (mTORC1), Safety of 3-Isopropyl-1H-pyrazole-5-carboxylic acid, the publication is Bioorganic & Medicinal Chemistry (2019), 27(6), 1099-1109, database is CAplus and MEDLINE.

Leucyl-tRNA synthetase (LRS) plays an important role in amino acid-dependent mTORC1 signaling, which is known to be associated with cellular metabolism and proliferation. Therefore, LRS-targeting small mols. that can suppress mTORC1 activation may provide an alternative strategy to current anticancer therapy. In this work, we developed a library of leucyladenylate sulfate analogs by extensively modifying three different pharmacophoric regions comprising adenine, ribose and leucine. Several effective compounds were identified by cell-based mTORC1 activation assays and further tested for anticancer activity. The selected compounds mostly exhibited selective cytotoxicity toward five different cancer cell lines, supporting the hypothesis that the LRS-mediated mTORC1 pathway is a promising alternative target to current therapeutic approaches.

Bioorganic & Medicinal Chemistry 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, Safety of 3-Isopropyl-1H-pyrazole-5-carboxylic acid.

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

Lee, Je-Heon published the artcileDiscovery of substituted indole derivatives as allosteric inhibitors of m⁶A-RNA methyltransferase, METTL3 -14 complex, Recommanded Product: 1H-Pyrazole-4-boronic acid, the publication is Drug Development Research (2022), 83(3), 783-799, database is CAplus and MEDLINE.

In this study, the discovery of the first allosteric inhibitor of the METTL3-14 complex I = [R¹ = H, CH₃; R² = (4-methoxycarbonylphenoxy), (4-carbamoylphenoxy), (4-carboxyphenoxy), etc.] and II [R³ = 4-Cl-Ph, 4-F-phenyl; R⁴ = Ph, benzyl, [4-(3,5-dichlorophenyl)phenyl], etc] was described based on structure-activity relationship (SAR) and optimization studies of the hit compound, 4-[2-[5-chloro-1-(diphenylmethyl)-2-methyl-1H-indol-3-yl]-ethoxy]benzoic acid. Compound II [R³ = 4-F-phenyl; R⁴ = [4-(3,5-dichlorophenyl)phenyl]] was optimized throughout the modifications of 4 different regions of the structure, and it displayed potent enzyme inhibitory activity of the METTL3-14 complex (IC₅₀ = 2.81μM) and an antiproliferative effect in the AML cell lines by suppressing the m6A level of mRNA. The inhibition mechanism and binding mode of II [R³ = 4-F-phenyl; R⁴ = [4-(3,5-dichlorophenyl)phenyl]], were based on the interaction of the reversible and noncompetitive inhibitory profile at the allosteric site along with selectivity for the METTL3-14 complex relative to each subunit enzyme or truncated complex enzyme.

Drug Development Research 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, Recommanded Product: 1H-Pyrazole-4-boronic acid.

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

Takeuchi, Craig S. published the artcileDiscovery of a Novel Class of Highly Potent, Selective, ATP-Competitive, and Orally Bioavailable Inhibitors of the Mammalian Target of Rapamycin (mTOR), Quality Control of 763120-58-7, the publication is Journal of Medicinal Chemistry (2013), 56(6), 2218-2234, database is CAplus and MEDLINE.

A series of novel, highly potent, selective, and ATP-competitive mammalian target of rapamycin (mTOR) inhibitors based on a benzoxazepine scaffold have been identified. Lead optimization resulted in the discovery of inhibitors with low nanomolar activity and greater than 1000-fold selectivity over the closely related PI3K kinases. Compound I (XL388) inhibited cellular phosphorylation of mTOR complex 1 (p-p70S6K, pS6, and p-4E-BP1) and mTOR complex 2 (pAKT (S473)) substrates. Furthermore, this compound displayed good pharmacokinetics and oral exposure in multiple species with moderate bioavailability. Oral administration of compound I to athymic nude mice implanted with human tumor xenografts afforded significant and dose-dependent antitumor activity.

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 C17H20ClN3, Quality Control of 763120-58-7.

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

Peterson, L. K. published the artcileMechanism of the transition metal-catalyzed reaction of 1,1′-carbonyldipyrazoles with aldehydes and ketones, Recommanded Product: 1H-Pyrazole-1-carbonyl chloride, the publication is Canadian Journal of Chemistry (1974), 52(13), 2367-74, database is CAplus.

The metal-catalyzed reaction of 1,1′-carbonyldipyrazoles with aldehydes or ketones to give 1,1′-alkylidenedipyrazoles and CO2, the latter being derived from the amide carbonyl group as shown by labeling experiments, is sensitive to electronic and steric substituent effects. Under comparable reaction conditions, 1,1′-carbonyldiimidazole, N-acetylpyrazole, and 1-pyrazole-N,N-diethylcarbonamide do not react with acetone while pyrazole-1-carbo(N’-phenylhydrazide) yields an anilino isocyanate dimer. These results are interpreted in terms of a mechanism that involves coordination of the metal ion at the 2,2′-N atoms of the pyrazole rings and heterolytic cleavage of an amide bond, followed by formation of a carbamate intermediate, decarboxylation, and metal ion exchange. Unsym. substituted 1,1′-carbonyldipyrazoles equilibrate thermally with their resp. sym. analogs by an intermol. exchange mechanism.

Canadian Journal of Chemistry 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, Recommanded Product: 1H-Pyrazole-1-carbonyl chloride.

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

Dehbi, Ouarda published the artcileBis(4-benzoyl-3-methyl-1-phenyl-4,5-dihydro-1H-pyrazol-5-olato-κ²O,O’)(methanol-κO)dioxidouranium(VI) methanol monosolvate, Safety of 4-Benzoyl-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one, the publication is Acta Crystallographica, Section E: Structure Reports Online (2012), 68(4), m457-m458, database is CAplus and MEDLINE.

In the title compound, [U(C₁₇H₁₃N₂O₂)₂O₂(MeOH)]·MeOH, the U^VI ion is coordinated by seven O atoms in a distorted pentagonal-bipyramidal geometry with two 3-methyl-1-phenyl-4-benzoyl-4,5-dihydro-1H-pyrazol-5-olate groups with two O atoms in a bidentate chelating coordination mode and by three O atoms, one of which is from a MeOH ligand. The crystal packing can be described by alternating layers of complex mols. along the a axis. The structure is stabilized by O-H···N and O-H···O H bonding and van der Waals interactions. Crystallog. data and at. coordinates are given.

Acta Crystallographica, Section E: Structure Reports Online 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, Safety of 4-Benzoyl-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one.

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

Mulyana, Yanyan published the artcileNew cobalt(II) and zinc(II) coordination frameworks incorporating a pyridyl-pyrazole ditopic ligand, Category: pyrazoles-derivatives, the publication is Dalton Transactions (2005), 1598-1601, database is CAplus and MEDLINE.

The metal-directed assembly of new mol. frameworks incorporating 4-(4-pyridyl)pyrazole (HL), containing non-linear coordination vectors, is presented. Three metallo-arrays of types [Co(LH₂)₂(NO₃)₄], [Co(LH₂)₂(H₂O)₄][NO₃]₄·H₂O and [Zn₂(L)₂Cl₂]·2EtOH. The cobalt(II) in [Co(LH₂)₂(NO₃)₄] displays distorted octahedral geometry with the two protonated pyridylpyrazole ligands coordinated through their pyrazole nitrogen atoms in a trans-orientation and the remaining four coordination sites occupied by nitrate anions. Two internal hydrogen bonds occur between each pyrazole NH and the oxygens of adjacent coordinated nitrato ligands. Short intermol. hydrogen bonds also occur between the two pyridinium hydrogens and bound nitrate ligands on different mols. to yield a two-dimensional hydrogen-bonded array. Two of these arrays interpenetrate to form an extended two dimensional layer. The two-dimensional layers stack throughout the crystal structure. A second product of type [Co(LH₂)₂(H₂O)₄][NO₃]₄·H₂O exists as two crystallog. independent forms that are chem. similar. In each form, the two protonated pyridylpyrazole ligands occupy trans positions about the cobalt with the remaining four coordination sites being filled by water mols. to yield a distorted octahedral coordination geometry. Intramol. hydrogen-bonding is observed between the two non-coordinated pyrazoyl nitrogen atoms and bound water oxygen atoms. The third complex, [Zn₂(L)₂Cl₂]·2EtOH, contains dimer units consisting of two zinc(II) ions bridged by two pyrazoylate groups in which the coordination geometry of each zinc approximates a tetrahedron. Each zinc is bound to two deprotonated pyridylpyrazolato ligands, one pyridyl group (from a different dimeric unit) and one chloro ligand. Each pyridyl nitrogen thus connects each of these zinc dimers to an adjacent dimer unit, forming a three-dimensional network containing small voids. The latter are occupied by ethanol mols. which form hydrogen bonds to the chloro ligands.

Dalton Transactions 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, Category: pyrazoles-derivatives.

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

Hong, Lin published the artcileCharacterization of a Cdc42 Protein Inhibitor and Its Use as a Molecular Probe, COA of Formula: C22H21N3O3S, the publication is Journal of Biological Chemistry (2013), 288(12), 8531-8543, database is CAplus and MEDLINE.

Cdc42 plays important roles in cytoskeleton organization, cell cycle progression, signal transduction, and vesicle trafficking. Overactive Cdc42 has been implicated in the pathol. of cancers, immune diseases, and neuronal disorders. Therefore, Cdc42 inhibitors would be useful in probing mol. pathways and could have therapeutic potential. Previous inhibitors have lacked selectivity and trended toward toxicity. We report here the characterization of a Cdc42-selective guanine nucleotide binding lead inhibitor that was identified by high throughput screening. A second active analog was identified via structure-activity relationship studies. The compounds demonstrated excellent selectivity with no inhibition toward Rho and Rac in the same GTPase family. Biochem. characterization showed that the compounds act as noncompetitive allosteric inhibitors. When tested in cellular assays, the lead compound inhibited Cdc42-related filopodia formation and cell migration. The lead compound was also used to clarify the involvement of Cdc42 in the Sin Nombre virus internalization and the signaling pathway of integrin VLA-4. Together, these data present the characterization of a novel Cdc42-selective allosteric inhibitor and a related analog, the use of which will facilitate drug development targeting Cdc42-related diseases and mol. pathway studies that involve GTPases.

Journal of Biological Chemistry 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, COA of Formula: C22H21N3O3S.

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

Waterson, Alex G. published the artcileDiphenylpyrazoles as replication protein A inhibitors, Synthetic Route of 13599-22-9, the publication is ACS Medicinal Chemistry Letters (2015), 6(2), 140-145, database is CAplus and MEDLINE.

Replication Protein A is the primary eukaryotic ssDNA binding protein that has a central role in initiating the cellular response to DNA damage. RPA recruits multiple proteins to sites of DNA damage via the N-terminal domain of the 70 kDa subunit (RPA70N). Here the authors describe the optimization of a diphenylpyrazole carboxylic acid series of inhibitors of these RPA-protein interactions. The authors evaluated substituents on the aromatic rings as well as the type and geometry of the linkers used to combine fragments, ultimately leading to submicromolar inhibitors of RPA70N protein-protein interactions.

ACS Medicinal Chemistry Letters published new progress about 13599-22-9. 13599-22-9 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Carboxylic acid,Benzene, name is 1,5-Diphenyl-1H-pyrazole-3-carboxylic acid, and the molecular formula is C7H7BN2O2, Synthetic Route of 13599-22-9.

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