Category: 930-36-9

Jagtap, Ajit Dhananjay published the artcile4-Substituted 2-amino-3,4-dihydroquinazolines with a 3-hairpin turn side chain as novel inhibitors of BACE-1, Recommanded Product: 1-Methylpyrazole, the publication is Bioorganic Chemistry (2020), 103135, database is CAplus and MEDLINE.

Herein, the authors report the identification, design, and synthesis of a series of 4-substituted 2-amino-3,4-dihydroquinazolines I [R¹ = Me, CH:CH₂, Bn, etc., R² = Me, cyclopropyl, (1-methyl-1H-pyrazol-4-yl)methyl] with hairpin turn side chains as novel inhibitors of BACE-1. The dihydroquinazoline derivatives were rationally designed by modifying the amide group and relocating the α-hydrophobic substituent on the hairpin turn side chain of lead compound II to the C4-position on the 3,4-dihydroquinazoline scaffold to facilitate interactions with the S₁, S₂ and S₁‘ subsites of BACE-1. Among these derivatives, two compounds exhibited potent BACE-1 inhibitory activity: 4-methyl-substituted derivative I [R¹ = Me, R² = (1-methyl-1H-pyrazol-4-yl)methyl] (BACE-1 CFA IC₅₀ = 0.38μM; BACE-1 WCA IC₅₀ = 0.14μM) and 4-cyclohexylmethyl-substituted derivative I [R¹ = cyclohexylmethyl, R² = (1-methyl-1H-pyrazol-4-yl)methyl] (BACE-1 CFA IC₅₀ = 0.49μM; BACE-1 WCA IC₅₀ = 0.14μM). The results suggest that the structural modifications maintain the hairpin turn topol. similar to that of compound II and provide an addnl. interaction with the S₂ subsite.

Bioorganic 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, Recommanded Product: 1-Methylpyrazole.

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

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

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

Graton, Jerome published the artcileHydrogen-Bond Accepting Properties of New Heteroaromatic Ring Chemical Motifs: A Theoretical Study, Recommanded Product: 1-Methylpyrazole, the publication is Journal of Chemical Information and Modeling (2016), 56(2), 322-334, database is CAplus and MEDLINE.

The prediction of hydrogen-bond (H-bond) acceptor ability is crucial in drug design. This important property is quantified in a large pK_BHX database of consistently measured values. We aim to expand the chem. diversity of the studied H-bond acceptors and to increase the range of H-bond strength considered. Two quantum chem. descriptors are contrasted, called ΔE(H) (the change in the energy of a topol. hydrogen atom upon complexation) and V_min (the local min. in the electrostatic potential on the H-bond accepting site). We performed a systematic anal. of the correlations between pK_BHX and V_min for an initial set of 106 compounds (including O- and N-containing subsets, as well as compounds including sulfur, chlorine, and π-bases). Correlations improve for family dependent subsets, and after outlier treatment, a set of 90 compounds was used to set up a linear equation to predict pK_BHX from V_min. This equation and a previously published equation, to predict pK_BHX from ΔE(H), were used to predict the pK_BHX values for 22 potentially biol. active heteroaromatic ring compounds, among which several structures still remain exptl. unavailable. H-Bond basicity of sp² nitrogen sites were consistently predicted with both descriptors. A worse agreement was found with carbonyl acceptor sites, with the stronger deviations observed for the lactam groups. It was shown that secondary interactions involving the neighboring NH group were influencing the results. Substitution of the NH group with an NMe group resulted in an improved consistency from both V_min and ΔE(H) predictions, the latter being more prominently affected by the Me substitution. Both approaches appear as efficient procedures for the H-bond ability prediction of novel heteroaromatic rings. Nevertheless, the ΔE(H) parameter presents slight chem. structure limitations and requires more detailed H-bond structure investigations.

Journal of Chemical Information and Modeling 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, Recommanded Product: 1-Methylpyrazole.

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

Alvarez, Eva Maria published the artcileLate-Stage Heteroarylation of Hetero(aryl)sulfonium Salts Activated by α-Amino Alkyl Radicals, Application of 1-Methylpyrazole, the publication is Angewandte Chemie, International Edition (2021), 60(24), 13609-13613, database is CAplus and MEDLINE.

We report a late-stage heteroarylation of aryl sulfonium salts through activation with α-amino alkyl radicals in a mechanistically distinct approach from previously reported halogen-atom transfer (XAT). The new mode of activation of aryl sulfonium salts proceeds in the absence of light and photoredox catalysts, engaging a wide range of heteroarenes. Furthermore, we demonstrate the applicability of this methodol. in synthetically useful cross-coupling transformations.

Angewandte Chemie, International Edition 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 of 1-Methylpyrazole.

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

Songsichan, T. published the artcileThiocyanation of Pyrazoles Using KSCN/K₂S₂O₈ Combination, Synthetic Route of 930-36-9, the publication is SynOpen (2018), 2(1), 0006-0016, database is CAplus.

A convenient and practical thiocyanation of pyrazoles employed a combination of KSCN and K₂S₂O₈ in DMSO (DMSO) was reported. The salient features of the present reaction included environmentally benign reagents, solvents and simple operation. The reaction showed wide functional group tolerance and gave moderate to excellent yields.

SynOpen 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 C5H6BNO2, Synthetic Route of 930-36-9.

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

Orazbayeva, Dina published the artcileDetermination of transformation products of unsymmetrical dimethylhydrazine in water using vacuum-assisted headspace solid-phase microextraction, Application of 1-Methylpyrazole, the publication is Journal of Chromatography A (2018), 30-36, database is CAplus and MEDLINE.

A new, sensitive and simple method based on vacuum-assisted headspace solid-phase microextraction (Vac-HSSPME) followed by gas chromatog.-mass-spectrometry (GC-MS), is proposed for the quantification of rocket fuel unsym. dimethylhydrazine (UDMH) transformation products in water samples. The target transformation products were: pyrazine, 1-methyl-1H-pyrazole, N-nitrosodimethylamine, N,N-dimethylformamide, 1-methyl-1H-1,2,4-triazole, 1-methyl-imidazole and 1H-pyrazole. For these analytes and within shorter sampling times, Vac-HSSPME yielded detection limits (0.5-100 ng L^-1) 3-10 times lower than those reported for regular HSSPME. Vac-HSSPME sampling for 30 min at 50 °C yielded the best combination of analyte responses and their standard deviations (<15%). 1-Formyl-2,2-dimethylhydrazine and formamide were discarded because of the poor precision and accuracy when using Vac-HSSPME. The recoveries for the rest of the analytes ranged between 80 and 119%. The modified Mininert valve and Thermogreen septum could be used for automated extraction as it ensured stable analyte signals even after long waiting times (>24 h). Finally, multiple Vac-HSSME proved to be an efficient tool for controlling the matrix effect and quantifying UDMH transformation products.

Journal of Chromatography A 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 of 1-Methylpyrazole.

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

Wietelmann, Ulrich published the artcileContinuous Processing of Concentrated Organolithiums in Flow Using Static and Dynamic Spinning Disc Reactor Technologies, Name: 1-Methylpyrazole, the publication is Organic Process Research & Development (2022), 26(5), 1422-1431, database is CAplus.

Organometallic reactions involving highly reactive organolithium reagents are widely used in organic synthesis. However, the use of organometallics in batch mode on a pilot and industrial scale is challenging for safety reasons and frequently requires expensive cryogenic process conditions. A change to continuous processing in flow mode can provide major advantages for process safety and economics. In this study, we compare static and dynamic flow reactor technologies for two important organolithium (butyllithium and hexyllithium)-enabled transformations: deprotonations and bromine/lithium exchange reactions. Using higher concentrated (≥3 M) butyllithium (BuLi) solutions, i.e., reaction mixtures with reduced hydrocarbon content, decreases the risk of reactor fouling and allows for increased space/time yields. In the flow mode, the observed reactions could be carried out under more convenient conditions, i.e., at higher temperatures compared to the batch mode, and the deprotonation reaction even at ambient temperature instead of -78°C. The formation of precipitates with the risk of clogging can be further reduced by changing from static flow to dynamic spinning disk reactor technol. The SpinPro reactor system from Flowid has been identified to ensure robust performance, as it tolerates salt precipitations and can provide excellent mass transfer conditions. Flow process technol. using concentrated organolithium products can provide unique benefits for the manufacturing of pharmaceutical intermediates, agrochem. products, and specialty chems.

Organic Process Research & Development 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 C20H23N3O2S, Name: 1-Methylpyrazole.

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

Shinozuka, Tsuyoshi published the artcileDiscovery of DS-1971a, a Potent, Selective Na_V1.7 Inhibitor, Category: pyrazoles-derivatives, the publication is Journal of Medicinal Chemistry (2020), 63(18), 10204-10220, database is CAplus and MEDLINE.

A highly potent, selective Na_V1.7 inhibitor, DS-1971a(I), has been discovered. Exploration of the left-hand Ph ring of sulfonamide derivatives (I and II) led to the discovery of novel series of cycloalkane derivatives with high Na_V1.7 inhibitory potency in vitro. As the right-hand heteroaromatic ring affected the mechanism-based inhibition liability of CYP3A4, replacement of this moiety resulted in the generation of 4-pyrimidyl derivatives Addnl., GSH adducts formation, which can cause idiosyncratic drug toxicity, was successfully avoided by this modification. An addnl. optimization led to the discovery of DS-1971a. In preclin. studies, DS-1971a demonstrated highly potent selective in vitro profile with robust efficacy in vivo. DS-1971a exhibited a favorable toxicol. profile, which enabled multiple-dose studies of up to 600 mg bid or 400 mg tid (1200 mg/day) administered for 14 days to healthy human males. DS-1971a is expected to exert potent efficacy in patients with peripheral neuropathic pain, with a favorable safety profile.

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 C22H23ClN4, Category: pyrazoles-derivatives.

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