Category: 930-36-9

Li, Wenjing published the artcileStereodivergent Synthesis of Alkenylpyridines via Pd/Cu Catalyzed C-H Alkenylation of Pyridinium Salts with Alkynes, Recommanded Product: 1-Methylpyrazole, the publication is Organic Letters (2020), 22(20), 7814-7819, database is CAplus and MEDLINE.

The first Pd/Cu catalyzed selective C2-alkenylation of pyridines with internal alkynes has been developed via the pyridinium salt activation strategy. Importantly, the configuration of the product alkenylpyridines could be tuned by the choice of the proper N-alkyl group of the pyridinium salts, thus allowing for both the Z- and E-alkenylpyridines synthesized with good regio- and stereoselectivity. A plausible mechanism was proposed based on the Hammett study and KIE experiment

Organic 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, Recommanded Product: 1-Methylpyrazole.

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

Shi, Xinzhe published the artcileC-H Bond Arylation of Pyrazoles at the β-Position: General Conditions and Computational Elucidation for a High Regioselectivity, Recommanded Product: 1-Methylpyrazole, the publication is Chemistry – A European Journal (2021), 27(17), 5546-5554, database is CAplus and MEDLINE.

Direct arylation of most five-membered ring heterocycles are generally easily accessible and strongly favored at the α-position using classical palladium-catalysis. Conversely, regioselective functionalization of such heterocycles at the concurrent β-position remains currently very challenging. Herein, authors report general conditions for regioselective direct arylation at the β-position of pyrazoles, while C-H α-position is free. By using aryl bromides as the aryl source and a judicious choice of solvent, the arylation reaction of variously N-substituted pyrazoles simply proceeds via β-C-H bond functionalization. The β-regioselectivity is promoted by a ligand-free palladium catalyst and a simple base without oxidant or further additive, and tolerates a variety of substituents on the bromoarene. DFT calculations revealed that a protic solvent such as 2-ethoxyethan-1-ol significantly enhances the acidity of the proton at β-position of the pyrazoles and thus favors this direct β-C-H bond arylation. This selective pyrazoles β-C-H bond arylation was successfully applied for the straightforward building of π-extended poly(hetero)aromatic structures via further Pd-catalyzed combined α-C-H intermol. and intramol. C-H bond arylation in an overall highly atom-economical process.

Chemistry – A European 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 C18H23N3O4S, Recommanded Product: 1-Methylpyrazole.

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

O’Sullivan, Leonie published the artcileRegioselective Synthesis of C3-Hydroxyarylated Pyrazoles, Safety of 1-Methylpyrazole, the publication is Journal of Organic Chemistry (2022), 87(1), 846-854, database is CAplus and MEDLINE.

The first regioselective route to C3-hydroxyarylated pyrazoles obtained through reaction of pyrazole N-oxides with arynes using mild conditions is reported. Importantly, this method does not require the C4 and C5 positions of the pyrazole to be functionalized to observe regioselectivity. Using this method, authors completed the synthesis of a recently reported JAK 1/2 inhibitor. Authors’ synthesis produces the desired product in 4 steps from com. available starting materials.

Journal of Organic 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, Safety of 1-Methylpyrazole.

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

Belyy, Alexander Yu. published the artcileA New Simple Procedure for the Synthesis of Heptamethyl Cyclohepta-1,3,5-triene-1,2,3,4,5,6,7-heptacarboxylate, COA of Formula: C4H6N2, the publication is Synlett (2018), 29(9), 1157-1160, database is CAplus.

A new and simple procedure for the synthesis of heptamethyl cyclohepta-1,3,5-triene-1,2,3,4,5,6,7-heptacarboxylate in a 51% yield was presented. An optimization of the reaction conditions was performed and a convenient protocol for the isolation of the reaction product was developed. The structure of the key electrophilic intermediate was determined by means of NMR spectroscopy and a plausible reaction mechanism was proposed.

Synlett 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, COA of Formula: C4H6N2.

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

Bachmann, Fabio published the artcileCytochrome P450 1A2 is the most important enzyme for hepatic metabolism of the metamizole metabolite 4-methylaminoantipyrine, Computed Properties of 930-36-9, the publication is British Journal of Clinical Pharmacology (2022), 88(4), 1885-1896, database is CAplus and MEDLINE.

Metamizole (dipyrone) is a prodrug not detectable in serum or urine after oral ingestion. The primary metabolite, 4-methylaminoantipyrine (4-MAA), can be N-demethylated to 4-aminoantipyrine (4-AA) or oxidized to 4-formylaminoantipyrine (4-FAA) by cytochrome P 450 (CYP)-dependent reactions. We aimed to identify the CYPs involved in 4-MAA metabolism and to quantify the effect of CYP inhibition on 4-MAA metabolism We investigated the metabolism of 4-MAA in vitro using CYP expressing supersomes and the pharmacokinetics of metamizole in the presence of CYP inhibitors in male subjects. The experiments in supersomes revealed CYP1A2 as the major CYP for 4-MAA N-demethylation and 4-FAA formation with CYP2C19 and CYP2D6 contributing to N-demethylation. In the clin. study, we investigated the influence of ciprofloxacin (CYP1A2 inhibitor), fluconazole (CYP2C19 inhibitor) and the combination ciprofloxacin/fluconazole on the pharmacokinetics of metamizole in n = 12 male subjects in a randomized, placebo-controlled, double-blind study. The geometric mean ratios for the area under the concentration-time curve of 4-MAA after/before treatment were 1.17 (90% CI 1.09-1.25) for fluconazole, 1.51 (90% CI 1.42-1.60) for ciprofloxacin and 1.92 (90% CI 1.81-2.03) for ciprofloxacin/fluconazole. Fluconazole increased the half-life of 4-MAA from 3.22 h by 0.47 h (95% CI 0.13-0.81, P < .05), ciprofloxacin by 0.69 h (95% CI 0.44-0.94, P < .001) and fluconazole/ciprofloxacin by 2.85 h (95% CI 2.48-3.22, P < .001). CYP1A2 is the major CYP for the conversion of 4-MAA to 4-AA and 4-FAA. The increase in 4-MAA exposure by the inhibition of CYP1A2 and by the combination CYP1A2/CYP2C19 may be relevant for dose-dependent adverse reactions of 4-MAA.

British Journal of Clinical Pharmacology 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

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

Bachmann, Fabio published the artcileCytochrome P450 1A2 is the most important enzyme for hepatic metabolism of the metamizole metabolite 4-methylaminoantipyrine, Computed Properties of 930-36-9, the publication is British Journal of Clinical Pharmacology (2022), 88(4), 1885-1896, database is CAplus and MEDLINE.

Metamizole (dipyrone) is a prodrug not detectable in serum or urine after oral ingestion. The primary metabolite, 4-methylaminoantipyrine (4-MAA), can be N-demethylated to 4-aminoantipyrine (4-AA) or oxidized to 4-formylaminoantipyrine (4-FAA) by cytochrome P 450 (CYP)-dependent reactions. We aimed to identify the CYPs involved in 4-MAA metabolism and to quantify the effect of CYP inhibition on 4-MAA metabolism We investigated the metabolism of 4-MAA in vitro using CYP expressing supersomes and the pharmacokinetics of metamizole in the presence of CYP inhibitors in male subjects. The experiments in supersomes revealed CYP1A2 as the major CYP for 4-MAA N-demethylation and 4-FAA formation with CYP2C19 and CYP2D6 contributing to N-demethylation. In the clin. study, we investigated the influence of ciprofloxacin (CYP1A2 inhibitor), fluconazole (CYP2C19 inhibitor) and the combination ciprofloxacin/fluconazole on the pharmacokinetics of metamizole in n = 12 male subjects in a randomized, placebo-controlled, double-blind study. The geometric mean ratios for the area under the concentration-time curve of 4-MAA after/before treatment were 1.17 (90% CI 1.09-1.25) for fluconazole, 1.51 (90% CI 1.42-1.60) for ciprofloxacin and 1.92 (90% CI 1.81-2.03) for ciprofloxacin/fluconazole. Fluconazole increased the half-life of 4-MAA from 3.22 h by 0.47 h (95% CI 0.13-0.81, P < .05), ciprofloxacin by 0.69 h (95% CI 0.44-0.94, P < .001) and fluconazole/ciprofloxacin by 2.85 h (95% CI 2.48-3.22, P < .001). CYP1A2 is the major CYP for the conversion of 4-MAA to 4-AA and 4-FAA. The increase in 4-MAA exposure by the inhibition of CYP1A2 and by the combination CYP1A2/CYP2C19 may be relevant for dose-dependent adverse reactions of 4-MAA.

British Journal of Clinical Pharmacology 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

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

Lakhey, Nivrutti published the artcileToxicity of azoles towards the anaerobic ammonium oxidation (anammox) process, Safety of 1-Methylpyrazole, the publication is Journal of Chemical Technology and Biotechnology (2020), 95(4), 1057-1063, database is CAplus.

Azoles are an important class of compounds that are widely used as corrosion inhibitors in aircraft de-icing agents, cooling towers, semiconductor manufacturing and household dishwashing detergents. They also are important moieties in pharmaceutical drugs and fungicides. Azoles are widespread emerging contaminants occurring frequently in water bodies. Azole compounds can potentially cause inhibition towards key biol. processes in natural ecosystems and wastewater treatment processes. Of particular concern is the inhibition of azoles to the nitrification process (aerobic oxidation of ammonium). This study investigated the acute toxicity of azole compounds towards the anaerobic ammonia oxidation (anammox) process, which is an important environmental biotechnol. gaining traction for nutrient-nitrogen removal during wastewater treatment. In this study, using batch bioassay techniques, the anammox toxicity of eight commonly occurring azole compounds was evaluated. The results show that 1H-benzotriazole and 5-methyl-1H-benzotriazole had the highest inhibitory effect on the anammox process, causing 50% decrease in anammox activity (IC₅₀) at concentrations of 19.6 and 17.8 mg L^-1, resp. 1H-imidazole caused less severe toxicity with an IC₅₀ of 79.4 mg L^-1. The other azole compounds were either nontoxic (1H-pyrazole, 1H-1,2,4-triazole and 1-methyl-pyrazole) or at best mildly toxic (1H-benzotriazole-5-carboxylic acid and 3,5-dimethyl-1H-pyrazole) towards the anammox bacteria at the concentrations tested. This study showed that most azole compounds tested displayed mild to low or no toxicity towards the anammox bacteria. The anammox bacteria were found to be far less sensitive to azoles compared to nitrifying bacteria.

Journal of Chemical Technology and Biotechnology 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, Safety of 1-Methylpyrazole.

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