Month: November 2022

Liang, Jun published the artcileFrom a novel HTS hit to potent, selective, and orally bioavailable KDM5 inhibitors, Related Products of pyrazoles-derivatives, the publication is Bioorganic & Medicinal Chemistry Letters (2017), 27(13), 2974-2981, database is CAplus and MEDLINE.

A high-throughput screening (HTS) of the Genentech/Roche library identified a novel, uncharged scaffold as a KDM5A inhibitor. Lacking insight into the binding mode, initial attempts to improve inhibitor potency failed to improve potency, and synthesis of analogs was further hampered by the presence of a C-C bond between the pyrrolidine and pyridine. Replacing this with a C-N bond significantly simplified synthesis, yielding pyrazole analog, [3-(4-bromo-1H-pyrazol-1-yl)-1-pyrrolidinyl][5-(1-methylethyl)-1H-pyrazol-3-yl]methanone (35), of which the authors obtained a co-crystal structure with KDM5A. Using structure-based design approach, the authors identified, N-[(3R)-1-[[5-(1-methylethyl)-1H-pyrazol-3-yl]carbonyl]-3-pyrrolidinyl]cyclopropanecarboxamide (50), with improved biochem., cell potency and reduced MW and lower lipophilicity (Log D) compared with the original hit. Furthermore, 50 showed lower clearance than [5-(1-methylethyl)-1H-pyrazol-3-yl][(3S)-3-[6-methyl-4-(1-methyl-1H-pyrazol-4-yl)-2-pyridinyl]-1-pyrrolidinyl]methanone (9) in mice. In combination with its remarkably low plasma protein binding (PPB) in mice (40%), oral dosing of 50 at 5 mg/kg resulted in unbound C_max ∼2-fold of its cell potency (PC9 H3K4Me3 0.96 μM), meeting the authors’ criteria for an in vivo tool compound from a new scaffold.

Bioorganic & Medicinal Chemistry Letters 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, Related Products of pyrazoles-derivatives.

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

Oh, Sangmi published the artcileIdentification of Piperidine-3-carboxamide Derivatives Inducing Senescence-like Phenotype with Antimelanoma Activities, Recommanded Product: (1H-Pyrazol-5-yl)boronic acid, the publication is ACS Medicinal Chemistry Letters (2021), 12(4), 563-571, database is CAplus and MEDLINE.

This study evaluated the potential use of senescence-inducing small mols. in the treatment of melanoma. We screened com. available small-mol. libraries with high-throughput screening and high-content screening image-based technol. Our findings showed an initial hit with the embedded N-arylpiperidine-3-carboxamide scaffold induced senescence-like phenotypic changes in human melanoma A375 cells without serious cytotoxicity against normal cells. A focused library containing diversely modified analogs were constructed and examined to evaluate the structure-activity relationship of N-arylpiperidine-3-carboxamide derivatives starting from hit 1. This work identified a novel compound with remarkable antiproliferative activity in vitro and demonstrated the key structural moieties within.

ACS Medicinal Chemistry Letters 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, Recommanded Product: (1H-Pyrazol-5-yl)boronic acid.

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

Kaur, Mahaldeep published the artcileThe Indigenous Volatile Inhibitor 2-Methyl-2-butene Impacts Biofilm Formation and Interspecies Interaction of the Pathogenic Mucorale Rhizopus arrhizus, Recommanded Product: 4-(5-(4-Methoxyphenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)benzenesulfonamide, the publication is Microbial Ecology (2022), 83(2), 506-512, database is CAplus and MEDLINE.

2-Methyl-2-butene has recently been reported to be a quorum-based volatile self-inhibitor of spore germination and growth in pathogenic Mucorale Rhizopus arrhizus. The present study aimed to elucidate if this compound can influence R. arrhizus biofilm formation and interspecies interaction. The compound was found to significantly decrease R. arrhizus biofilm formation (p < 0.001), with nearly 25% and 50% lesser biomass in the biofilms cultured with exposure to 4 and 32μg/mL of 2-methyl-2-butene, resp. The growth of pre-formed biofilms was also impacted, albeit to a lesser extent. Addnl., 2-methyl-2-butene was found to self-limit R. arrhizus growth during interspecies interaction with Staphylococcus aureus and was detected at a substantially greater concentration in the headspace of co-cultures (2338.75μg/mL) compared with monocultures (69.52μg/mL). Some of the C5 derivatives of this compound (3-methyl-1-butanol, 2-methyl-2-butanol, and 3-methyl-1-butyne) were also observed to partially mimic its action, such as inhibition of spore germination, but did not impact R. arrhizus biofilm formation. Finally, the treated R. arrhizus displayed changes in fungal morphol. suggestive of cytoskeletal alterations, such as filopodia formation, blebs, increased longitudinal folds and/or corrugations, and finger-like and sheet-like surface protrusions, depending upon the concentration of the compound(s) and the planktonic or biofilm growth mode.

Microbial Ecology 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

Siu, Tony published the artcileThe discovery of reverse tricyclic pyridone JAK2 inhibitors. Part 2: Lead optimization, Product Details of C3H5BN2O2, the publication is Bioorganic & Medicinal Chemistry Letters (2014), 24(6), 1466-1471, database is CAplus and MEDLINE.

This communication discusses the discovery of novel reverse tricyclic pyridones as inhibitors of Janus kinase 2 (JAK2). By using a kinase cross screening approach coupled with mol. modeling, a unique inhibitor-water interaction was discovered to impart excellent broad kinase selectivity. Improvements in intrinsic potency were achieved by utilizing a rapid library approach, while targeted structural changes to lower lipophilicity led to improved rat pharmacokinetics. This multi-pronged approach led to the identification of 31, which demonstrated encouraging rat pharmacokinetics, in vivo potency, and excellent off-target kinase selectivity.

Bioorganic & Medicinal Chemistry Letters 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 C14H28O5S, Product Details of C3H5BN2O2.

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

Malysheva, Svetlana F. published the artcileCatalyst-free addition of secondary phosphine chalcogenides to pyrazolecarbaldehydes, Computed Properties of 930-36-9, the publication is Mendeleev Communications (2019), 29(6), 683-685, database is CAplus.

(Chalcogenophosphoryl)hydroxymethyl-substituted pyrazoles were obtained by catalyst-free reaction between 4- and 5-pyrazolecarbaldehydes and secondary phosphine chalcogenides R₂P(X)H [R = Ph, (CH₂)₂Ph, X = O, S, Se] at 23-50° in toluene.

Mendeleev Communications 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, Computed Properties of 930-36-9.

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

Naus, Petr published the artcileCytostatic and antiviral 6-arylpurine ribonucleosides IX. synthesis and evaluation of 6-substituted 3-deazapurine ribonucleosides, Application In Synthesis of 724710-02-5, the publication is Collection of Czechoslovak Chemical Communications (2008), 73(5), 665-678, database is CAplus.

A series of 3-deazapurine ribonucleosides bearing diverse C-substituents (alkyl, aryl and heteroaryl) in the position 6 were prepared by Pd-catalyzed cross-coupling reactions of either free 6-chloro-3-deazapurine ribonucleoside or its acetyl protected congener followed by deprotection. An improved synthesis of the starting 4-chloro-1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-1H-imidazo[4,5-c]pyridine was developed by the application of Vorbruggen glycosylation of silylated nucleobase with 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose. None of title compounds showed any considerable cytostatic or antiviral activity.

Collection of Czechoslovak Chemical Communications 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, Application In Synthesis of 724710-02-5.

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

Ivachtchenko, Alexandre V. published the artcileSynthesis of pinacol esters of 1-alkyl-1H-pyrazol-5-yl- and 1-alkyl-1H-pyrazol-4-ylboronic acids, SDS of cas: 847818-66-0, the publication is Journal of Heterocyclic Chemistry (2004), 41(6), 931-939, database is CAplus.

1-Substituted pyrazolylboronic acids and their pinacol esters were prepared by lithiation-borylation reaction sequence starting from bromopyrazoles. Alkylation of 4-bromo-1H-pyrazole gave 1-alkyl-4-bromo-1H-pyrazoles, which were lithiated at -80° and borylated with B(OMe)₃ to give 1-R-1H-pyrazole-4-boronic acids [4a–g, R = Me, Et, Pr, (CH₂)₂CHMe₂, (CH₂)₂OMe, (CH₂)₃NMe₂, (CH₂)₂CH(OEt)₂]. Lithiation of 4-bromo-1-(2-dimethylaminoethyl)-1H-pyrazole (2h) gave 5-lithio-derivative, which on borylation afforded 1-R¹-4-Br-1H-pyrazole-5-boronic acid (8). Boronic acids 4a–g are unstable and were deborylated slowly due to hydrolysis by traces of water; the stability of boryl derivatives can be greatly enhanced by converting to corresponding pinacol boronates (10a–g). Direct lithiation of 1-R²-1H-pyrazoles by BuLi at -20° afforded 5-lithio-derivatives, which were converted to corresponding 1-R²-1H-pyrazole-5-boronic acids [17a–e; R² = Me, ⁱBu, Pr, (CH₂)₂CHMe₂, (CH₂)₂CH(OEt)₂] and their pinacol boronates (18a–e, same R²). The key step in the described methodol. is the regioselective lithiation of the pyrazole ring. The synthesized pinacolates are stable under prolonged storage and can be used as convenient reagents in organic synthesis.

Journal of Heterocyclic Chemistry published new progress about 847818-66-0. 847818-66-0 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Boronic Acids,Boronic Acids,Boronic acid and ester, name is (1-Isopentyl-1H-pyrazol-5-yl)boronic acid, and the molecular formula is C8H15BN2O2, SDS of cas: 847818-66-0.

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

Ivachtchenko, Alexandre V. published the artcileSynthesis of pinacol esters of 1-alkyl-1H-pyrazol-5-yl- and 1-alkyl-1H-pyrazol-4-ylboronic acids, Quality Control of 847818-64-8, the publication is Journal of Heterocyclic Chemistry (2004), 41(6), 931-939, database is CAplus.

1-Substituted pyrazolylboronic acids and their pinacol esters were prepared by lithiation-borylation reaction sequence starting from bromopyrazoles. Alkylation of 4-bromo-1H-pyrazole gave 1-alkyl-4-bromo-1H-pyrazoles, which were lithiated at -80° and borylated with B(OMe)₃ to give 1-R-1H-pyrazole-4-boronic acids [4a–g, R = Me, Et, Pr, (CH₂)₂CHMe₂, (CH₂)₂OMe, (CH₂)₃NMe₂, (CH₂)₂CH(OEt)₂]. Lithiation of 4-bromo-1-(2-dimethylaminoethyl)-1H-pyrazole (2h) gave 5-lithio-derivative, which on borylation afforded 1-R¹-4-Br-1H-pyrazole-5-boronic acid (8). Boronic acids 4a–g are unstable and were deborylated slowly due to hydrolysis by traces of water; the stability of boryl derivatives can be greatly enhanced by converting to corresponding pinacol boronates (10a–g). Direct lithiation of 1-R²-1H-pyrazoles by BuLi at -20° afforded 5-lithio-derivatives, which were converted to corresponding 1-R²-1H-pyrazole-5-boronic acids [17a–e; R² = Me, ⁱBu, Pr, (CH₂)₂CHMe₂, (CH₂)₂CH(OEt)₂] and their pinacol boronates (18a–e, same R²). The key step in the described methodol. is the regioselective lithiation of the pyrazole ring. The synthesized pinacolates are stable under prolonged storage and can be used as convenient reagents in organic synthesis.

Journal of Heterocyclic Chemistry published new progress about 847818-64-8. 847818-64-8 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Pyrazole,Boronic Acids,Boronic acid and ester, name is (1-Isobutyl-1H-pyrazol-5-yl)boronic acid, and the molecular formula is C7H13BN2O2, Quality Control of 847818-64-8.

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

Ul′yanovskii, Nikolay V. published the artcileRapid quantification and screening of nitrogen-containing rocket fuel transformation products by vortex assisted liquid-liquid microextraction and gas chromatography – high-resolution Orbitrap mass spectrometry, Formula: C4H6N2, the publication is Microchemical Journal (2021), 106821, database is CAplus.

Existing and newly developed technologies for clean-up of wastewaters and soils contaminated with rocket fuel unsym. dimethylhydrazine (UDMH) are based on the oxidative treatment, as well as gasification in supercritical water. Being easily transformed by a radical mechanism, UDMH is capable of producing an extremely wide range of potentially hazardous nitrogen-containing products. Their identification and simultaneous quantification at low concentrations in water samples by gas chromatog. is a challenging task requiring a matrix change. We proposed a combination of dispersive vortex-assisted liquid-liquid microextraction (VALLME) of analytes followed by gas chromatog. – Orbitrap mass spectrometry allowing simultaneous target anal. and non-targeted screening. Dichloromethane and chloroform provided rapid (10 min) and effective extraction of most of UDMH transformation products. The maximum recoveries were achieved by alkalizing and saturating the aqueous samples with ammonium sulfate. The use of pyridine-d5 as an internal standard allowed developing an approach to the simultaneous determination of 24 compounds of various classes with detection limits for the most analytes in the range 0.02-1.1 μg L^-1 and accuracy of 81-117% with low-cost, simple, and rapid sample preparation procedure. Extraction with a 100 μL of chloroform allowed further increasing sensitivity up to one order of magnitude and attaining LOD values for 20 compounds in the range of 0.002-0.1 μg L^-1 comparable with that obtained by vacuum-assisted headspace solid-phase microextraction The developed method was validated and tested for the analyses of real samples – degraded aqueous solution of rocket fuel, products of UDMH treatment in supercritical water and aqueous extract of soil from the place of carrier rocket accidental crash. Twenty-nine compounds that were not previously described as UDMH transformation products were tentatively identified.

Microchemical Journal 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 C10H14O, Formula: C4H6N2.

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

Kasparkova, Jana published the artcileNovel cis-Pt(II) complexes with alkylpyrazole ligands: synthesis, characterization, and unusual mode of anticancer action, Quality Control of 930-36-9, the publication is Bioinorganic Chemistry and Applications (2022), 1717200, database is CAplus and MEDLINE.

One concept of improving anticancer effects of conventional platinum-based antitumor drugs consists of conjugating these compounds with other biol. (antitumor) active agents, acting by a different mechanism. Here, we present synthesis, physicochem. characterization, biol. effects, and mechanisms of action of four new analogs of conventional cisplatin, namely, cis-Pt(II) complexes containing either Me or Et pyrazole N-donor ligands and chlorido or iodido ligands. It is noteworthy that while chlorido complexes display activity in a variety of cancer cell lines comparable to cisplatin, iodido complexes are considerably more potent due to their enhanced hydrophobicity and consequently enhanced cellular accumulation. Moreover, all of the studied Pt(II) alkylpyrazole complexes display a higher selectivity for tumor cells and effectively overcome the acquired resistance to cisplatin. Further results focused on the mechanism of action of the studied complexes and showed that in contrast to cisplatin and several platinum-based antitumor drugs, DNA damage by the investigated Pt(II)-alkylpyrazole complexes does not play a major role in their mechanism of action. Our findings demonstrate that inhibition of the tubulin kinesin Eg5, which is essential for forming a functional mitotic spindle, plays an important role in their mechanism of antiproliferative action.

Bioinorganic Chemistry and Applications 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, Quality Control of 930-36-9.

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