Category: pyrazoles-derivatives

Lee, Dahye published the artcileDiscovery of Novel Pyruvate Dehydrogenase Kinase 4 Inhibitors for Potential Oral Treatment of Metabolic Diseases, Name: (1-(1-(tert-Butoxycarbonyl)piperidin-4-yl)-1H-pyrazol-4-yl)boronic acid, the publication is Journal of Medicinal Chemistry (2019), 62(2), 575-588, database is CAplus and MEDLINE.

Pyruvate dehydrogenase kinase 4 (PDK4) activation is associated with metabolic diseases including hyperglycemia, insulin resistance, allergies, and cancer. Structural modifications of hit anthraquinone led to the identification of a new series of allosteric PDK4 inhibitors. Among this series, compound 8c showed promising in vitro activity with an IC₅₀ value of 84 nM. Good metabolic stability, pharmacokinetic profiles, and possible metabolites were suggested. Compound 8c improved glucose tolerance in diet-induced obese mice and ameliorated allergic reactions in a passive cutaneous anaphylaxis mouse model. Addnl., compound 8c exhibited anticancer activity by controlling cell proliferation, transformation, and apoptosis. From the mol. docking studies, compound 8c displayed optimal fitting in the lipoamide binding site (allosteric) with a full fitness, providing a new scaffold for drug development toward PDK4 inhibitors.

Journal of Medicinal Chemistry published new progress about 1190875-39-8. 1190875-39-8 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Piperidine,Boronic acid and ester,Amide,Boronic Acids,Boronic Acids,Boronic acid and ester,, name is (1-(1-(tert-Butoxycarbonyl)piperidin-4-yl)-1H-pyrazol-4-yl)boronic acid, and the molecular formula is C13H22BN3O4, Name: (1-(1-(tert-Butoxycarbonyl)piperidin-4-yl)-1H-pyrazol-4-yl)boronic acid.

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

Li, Ao published the artcilePorphyrin-Catalyzed Oxidation of N-Substituted Tetrahydroisoquinolines to Dihydroisoquinolones, COA of Formula: C3H5BN2O2, the publication is Synlett (2021), 32(7), 679-684, database is CAplus.

A visible-light-induced direct α-oxygenation of N-substituted 1,2,3,4-tetrahydroisoquinoline derivatives has been successfully developed. Tetraphenylporphyrinatozinc(II) has been identified as an effective and inexpensive photocatalyst for this transformation with a wide range of substrates. This protocol provides a convenient route to the desired products I (Ar = C₆H₅, pyrazol-3-yl, 4-MeC₆H₄, etc.; R = H, 6,7-OMe₂) in moderate to good yields at room temperature under air.

Synlett 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, COA of Formula: C3H5BN2O2.

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

Yang, Shu-Wei published the artcileBenzimidazole analogs as WTA biosynthesis inhibitors targeting methicillin resistant Staphylococcus aureus, Safety of 1H-Pyrazole-4-boronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2016), 26(19), 4743-4747, database is CAplus and MEDLINE.

A series of benzimidazole analogs have been synthesized to improve the profile of the previous lead compounds tarocin B. The syntheses, structure-activity relationships, and selected biochem. data of these analogs are described. The optimization efforts allowed the identification of I, a fluoro-substituted benzimidazole, exhibiting potent TarO inhibitory activity and typical profile for a wall teichoic acid (WTA) biosynthesis inhibitor. Compound I displayed a potent synergistic and bactericidal effect in combination with imipenem against diverse methicillin-resistant Staphylococci.

Bioorganic & Medicinal Chemistry Letters 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 C5H7BO2S, Safety of 1H-Pyrazole-4-boronic acid.

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

Parmar, Narsidas J. published the artcileSolvent-free, one-pot synthesis and biological evaluation of some new dipyrazolo [3,4-b:4′,3′-e]pyranylquinolones and their precursors, Related Products of pyrazoles-derivatives, the publication is Medicinal Chemistry Research (2014), 23(1), 42-56, database is CAplus.

One-pot synthesis of 24 new compounds, belonging to three families; dipyrazolo[3,4-b:4′,3′-e]pyranylquinolones and its precursors (pyrazolonylidene)methylquinolones and 4,4′-[(quinolinyl)methylene]bispyrazols, has been achieved in the presence of catalyst tetrabutylammonium hydrogen sulfate (TBA-HS) in solvent-free conditions. In addition to assuring chromatog.-free product isolation, this method had also allowed the reaction to proceed in a regio-selective manner provided the temperature and amount of pyrazolone are varied. At 100 °C, while 1:1 mixture of aldehyde 3 and pyrazolone 4 underwent Knoevenagel condensation, same reactants taken in ratio of 1:2 mainly domino/Knoevenagel-Michael reaction. At 120 °C, however, the domino/Knoevenagel-Michael-adducts converted into cyclized product, highlighting a new domino/Knoevenagel-Michael-cyclization synthetic sequence. The structure of all heterocycles has been confirmed by mass, IR and NMR spectral data. Based on 2D NMR NOESY experiment, it was also confirmed that the formation of only Z’ configuration of Knoevenagel alkene took place in the transformation. All are good antitubercular agents as they were found to be active against M. tuberculosis H37RV, in addition to being found active against three Gram-pos. (Streptococcus pneumoniae, Clostridium tetani, Bacillus subtilis) and three Gram-neg. (Salmonella typhi, Vibrio cholerae, Escherichia coli) bacteria, resp.

Medicinal Chemistry Research 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, Related Products of pyrazoles-derivatives.

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

Parmar, Narsidas J. published the artcileTriethylammonium acetate-mediated domino-Knoevenagel-hetero-Diels-Alder reaction: synthesis of some angular polyheterocycles, Computed Properties of 14580-22-4, the publication is Monatshefte fuer Chemie (2013), 144(6), 865-878, database is CAplus.

A solvent-cum catalyst, ionic liquid triethylammonium acetate-mediated one-pot procedure for the synthesis of some new angular benzopyrano[3,4-c]pyrano-fused pyrazoles, e.g., I, all of which incorporate a tertiary ring junction carbon, has been developed. The stereochem. of the products has been confirmed by single-crystal X-ray diffraction data.

Monatshefte fuer Chemie 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

Nguyen, Diem N. published the artcileCalcitonin gene-related peptide (CGRP) receptor antagonists: Investigations of a pyridinone template, Related Products of pyrazoles-derivatives, the publication is Bioorganic & Medicinal Chemistry Letters (2008), 18(2), 755-758, database is CAplus and MEDLINE.

In our effort to find potent, orally bioavailable CGRP receptor antagonists for the treatment of migraine, a novel series based on a pyridinone template was investigated. After optimizing the privileged structure and the placement of the attached Ph ring, systematic SAR was carried out on both the N-alkyl and C-5 aryl substituents. Several analogs with good potency and pharmacokinetic profiles were identified.

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 C3H5BN2O2, Related Products of pyrazoles-derivatives.

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

Dorgan, Roderick J. J. published the artcileN-Alkyl and N-acyl derivatives of 3(5)-aminopyrazole, Safety of 3-Acetamidopyrazole, the publication is Journal of Chemical Research, Synopses (1979), 198, database is CAplus.

3(5)-Aminopyrazole (I) underwent benzylation on the exocyclic N to give II [R = H, R¹ = R² = CH₂Ph; R = R¹ = H, R² = CH₂Ph (III)] whereas acetylation gave II (R = R¹ = Ac, R² = H), which on subsequent benzylation gave II (R = CH₂Ph, R¹ = Ac, R² = H) and IV (R = CH₂Ph, R¹ = H, R² = Ac) (V). In the presence of MeCOCH₂CO₂Et, III gave the pyrazolo[1,5-a]pyrimidine VI (R = CH₂Ph) which was debenzylated to VI (R = H). PhCH₂NHNH₂ reacted with CH₂:CClCN to give IV (R = CH₂Ph, R¹ = R² = H) which on acetylation gave V. I with phthalic anhydride gave II (R = H, NR¹R² = phthalimido) which on benzylation and benzyloxymethylation gave II (R = CH₂Ph, R¹R² as before) and IV (R = CH₂OCH₂Ph, R¹R² as before), resp.

Journal of Chemical Research, Synopses published new progress about 3553-12-6. 3553-12-6 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Amine,Amide, name is 3-Acetamidopyrazole, and the molecular formula is C5H7N3O, Safety of 3-Acetamidopyrazole.

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

Dwyer, Michael P. published the artcileDiscovery of pyrazolo[1,5-a]pyrimidine-based CHK1 inhibitors: A template-based approach-Part 1, Recommanded Product: (1H-Pyrazol-5-yl)boronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2011), 21(1), 467-470, database is CAplus and MEDLINE.

The synthesis and hit-to-lead SAR development of a pyrazolo[1,5-a]pyrimidine hit I is described leading to a series of potent, selective CHK1 inhibitors such as compound II. The further utility of the pyrazolo[1,5-a]pyrimidine template for the development of potent, selective kinase inhibitors is detailed.

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 C3H5BN2O2, Recommanded Product: (1H-Pyrazol-5-yl)boronic acid.

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

Antolin, Albert A. published the artcileDistant Polypharmacology among MLP Chemical Probes, Quality Control of 71203-35-5, the publication is ACS Chemical Biology (2015), 10(2), 395-400, database is CAplus and MEDLINE.

Small mols. are essential tool compounds to probe the role of proteins in biol. and advance toward more efficient therapeutics. However, they are used without a complete knowledge of their selectivity across the entire proteome, at risk of confounding their effects due to unknown off-target interactions. Current state-of-the-art computational approaches to predicting the affinity profile of small mols. offer a means to anticipate potential nonobvious selectivity liabilities of chem. probes. The application of in silico target profiling on the full set of chem. probes from the NIH Mol. Libraries Program (MLP) resulted in the identification of biol. relevant in vitro affinities for proteins distantly related to the primary targets of ML006, ML123, ML141, and ML204, helping to lower the risk of their further use in chem. biol.

ACS Chemical Biology 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

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