pyrazoles-derivatives

Chen, Long-Wang published the artcileMetronidazole containing pyrazole derivatives potently inhibit tyrosyl-tRNA synthetase: design, synthesis, and biological evaluation, COA of Formula: C16H12N2O2, the publication is Chemical Biology & Drug Design (2016), 88(4), 592-598, database is CAplus and MEDLINE.

As an important enzyme in bacterial protein biosynthesis, tyrosyl-tRNA synthetase (TyrRS) has been an absorbing therapeutic target for exploring novel antibacterial agents. A series of metronidazole-based antibacterial agents has been synthesized and identified as TyrRS inhibitors with low cytotoxicity and significant antibacterial activity, especially against Gram-neg. organisms. Of the compounds obtained, I is the most potent agent which inhibited the growth of Pseudomonas aeruginosa ATCC 13525 (MIC = 0.98 μg/mL) and exhibited TryRS inhibitory activity (IC₅₀ = 0.92 μM). Docking simulation was performed to further understand its potency. Membrane-mediated apoptosis in P. aeruginosa was verified by flow cytometry.

Chemical Biology & Drug Design 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 C16H12N2O2, COA of Formula: C16H12N2O2.

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

Luo, Zhibo published the artcileDiscovery and optimization of selective RET inhibitors via scaffold hopping, Application of 2-Chloro-6-methyl-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine, the publication is Bioorganic & Medicinal Chemistry Letters (2021), 128149, database is CAplus and MEDLINE.

Aberrant alterations of rearranged during transfection (RET) have been identified as actionable drivers of multiple cancers, including thyroid carcinoma and lung cancer. Currently, several approved multikinase inhibitors such as vandetanib and cabozantinib demonstrate clin. activity in patients with RET-rearranged or RET-mutant cancers. However, the observed response rates are only modest and the ‘off-target’ toxicities resulted from the inhibition of other kinases is also a concern. Herein, we designed and synthesized a series of RET inhibitors based on the structure of selective RET inhibitor BLU-667 and investigated their biol. activities. We identified compound I as a novel potent and selective RET inhibitor with improved drug-like properties. Compound I exhibits a selective inhibitory profile with an inhibitory concentration 50 (IC₅₀) of 1.29 nM for RET and 1.97 (RET V804M) or 0.99 (RET M918T) for mutant RETs. The proliferation of Ba/F3 cells transformed with NSCLC related KIF5B-RET fusion was effectively suppressed by compound I (IC₅₀ = 19 nM). Addnl., compound 9 displayed less ‘off-target’ effects than BLU-667. In mouse xenograft models, compound I repressed tumor growth driven by KIF5B-RET-Ba/F3 cells in a dose-dependent manner. Based on its exceptional kinase selectivity, good potency and high exposure in tumor tissues, compound 9 represents a promising lead for the discovery of RET directed therapeutic agents and the study of RET-driven tumor biol.

Bioorganic & Medicinal Chemistry Letters published new progress about 851435-28-4. 851435-28-4 belongs to pyrazoles-derivatives, auxiliary class Imidazole,Pyrimidine,Chloride,Amine, name is 2-Chloro-6-methyl-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine, and the molecular formula is C9H10ClN5, Application of 2-Chloro-6-methyl-N-(5-methyl-1H-pyrazol-3-yl)pyrimidin-4-amine.

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

Zhang, Rong published the artcileIodine-Catalyzed Construction of Dihydrooxepines via 3-Methyl-5-Pyrazolones C-H Oxidation/Functionalization of Quinolines Cascade, COA of Formula: C10H9ClN2O, the publication is European Journal of Organic Chemistry (2021), 2021(27), 3807-3811, database is CAplus.

An efficient iodine-catalyzed [3+3+1] annulation for the construction of dihydrooxepine scaffolds with quinoline units was developed. This strategy involved a seven-membered dihydrooxepine with a broad substrate scope through a formal three-component tandem reaction. Further derivation of the target product produced a trioxabicycle scaffold, which formed the basic core of natural products and pharmaceutical mols.

European Journal of Organic Chemistry 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 C9H9BrO2, COA of Formula: C10H9ClN2O.

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

Liu, Qingsong published the artcileDiscovery and optimization of potent and selective benzonaphthyridinone analogs as small molecule mTOR inhibitors with improved mouse microsome stability, Recommanded Product: 1H-Pyrazole-4-boronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2011), 21(13), 4036-4040, database is CAplus and MEDLINE.

Starting from small mol. mTOR inhibitor Torin1, replacement of the piperazine ring with a Ph ring resulted in a new series of mTOR inhibitors (as exemplified by 10) that showed superior potency and selectivity for mTOR, along with significantly improved mouse liver microsome stability and a longer in vivo half-life.

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 C3H5BN2O2, Recommanded Product: 1H-Pyrazole-4-boronic acid.

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

Liu, Qingsong published the artcileDiscovery of 9-(6-Aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one (Torin2) as a potent, selective, and orally available mammalian target of rapamycin (mTOR) inhibitor for treatment of cancer, Name: 1H-Pyrazole-4-boronic acid, the publication is Journal of Medicinal Chemistry (2011), 54(5), 1473-1480, database is CAplus and MEDLINE.

The mTOR mediated PI3K/AKT/mTOR signal transduction pathway has been demonstrated to play a key role in a broad spectrum of cancers. Starting from the mTOR selective inhibitor 1 (Torin1), a focused medicinal chem. effort led to the discovery of an improved mTOR inhibitor 3 (Torin2, I), which possesses an EC₅₀ of 0.25 nM for inhibiting cellular mTOR activity. Compound 3 exhibited 800-fold selectivity over PI3K (EC₅₀: 200 nM) and over 100-fold binding selectivity relative to 440 other protein kinases. Compound 3 has significantly improved bioavailability (54%), metabolic stability, and plasma exposure relative to compound 1.

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 C3H5BN2O2, Name: 1H-Pyrazole-4-boronic acid.

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

Murphy-Benenato, Kerry published the artcileIdentification through structure-based methods of a bacterial NAD⁺-dependent DNA ligase inhibitor that avoids known resistance mutations, Related Products of pyrazoles-derivatives, the publication is Bioorganic & Medicinal Chemistry Letters (2014), 24(1), 360-366, database is CAplus and MEDLINE.

In an attempt to identify novel inhibitors of NAD⁺-dependent DNA ligase (LigA) that are not affected by a known resistance mutation in the adenosine binding pocket, a detailed anal. of the binding sites of a variety of bacterial ligases was performed. This anal. revealed several similarities to the adenine binding region of kinases, which enabled a virtual screen of known kinase inhibitors. From this screen, a thienopyridine scaffold was identified that was shown to inhibit bacterial ligase. Further characterization through structure and enzymol. revealed the compound was not affected by a previously disclosed resistance mutation in Streptococcus pneumoniae LigA, Leu75Phe. A subsequent medicinal chem. program identified substitutions that resulted in an inhibitor with moderate activity across various Gram-pos. bacterial LigA enzymes.

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

Pham, Thanh Truc published the artcileNovel 1,2-dihydroquinazolin-2-ones: Design, synthesis, and biological evaluation against Trypanosoma brucei, Category: pyrazoles-derivatives, the publication is Bioorganic & Medicinal Chemistry Letters (2017), 27(16), 3629-3635, database is CAplus and MEDLINE.

In 2014, a published report of the high-throughput screen of >42,000 kinase inhibitors from GlaxoSmithKline against T. brucei identified 797 potent and selective hits. From this rich data set, the authors selected NEU-<0001101≥(1) for hit-to-lead optimization. Through the authors’ preliminary compound synthesis and SAR studies, the authors confirmed the previously reported activity of 4-phenyl-6-(pyridin-4-yl)quinazolin-2(1H)-one in a T. brucei cell proliferation assay and have identified alternative groups to replace the pyridyl ring in 4-phenyl-6-(pyridin-4-yl)quinazolin-2(1H)-one. Pyrazole 24 achieves improvements in both potency and lipophilicity relative to 4-phenyl-6-(pyridin-4-yl)quinazolin-2(1H)-one , while also showing good in vitro metabolic stability. The SAR developed on 24 provides new directions for further optimization of this novel scaffold for anti-trypanosomal drug discovery.

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 C3H5BN2O2, Category: pyrazoles-derivatives.

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

Pham, Thanh Truc published the artcileNovel 1,2-dihydroquinazolin-2-ones: Design, synthesis, and biological evaluation against Trypanosoma brucei, Name: (1H-Pyrazol-5-yl)boronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2017), 27(16), 3629-3635, database is CAplus and MEDLINE.

In 2014, a published report of the high-throughput screen of >42,000 kinase inhibitors from GlaxoSmithKline against T. brucei identified 797 potent and selective hits. From this rich data set, the authors selected NEU-<0001101≥(1) for hit-to-lead optimization. Through the authors’ preliminary compound synthesis and SAR studies, the authors confirmed the previously reported activity of 4-phenyl-6-(pyridin-4-yl)quinazolin-2(1H)-one in a T. brucei cell proliferation assay and have identified alternative groups to replace the pyridyl ring in 4-phenyl-6-(pyridin-4-yl)quinazolin-2(1H)-one. Pyrazole 24 achieves improvements in both potency and lipophilicity relative to 4-phenyl-6-(pyridin-4-yl)quinazolin-2(1H)-one , while also showing good in vitro metabolic stability. The SAR developed on 24 provides new directions for further optimization of this novel scaffold for anti-trypanosomal drug discovery.

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, Name: (1H-Pyrazol-5-yl)boronic acid.

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

Bardhan, Sujata published the artcileHeteroaryl ethers by oxidative palladium catalysis of pyridotriazol-1-yloxy pyrimidines with arylboronic acids, Formula: C3H5BN2O2, the publication is Organic Letters (2009), 11(12), 2511-2514, database is CAplus and MEDLINE.

The oxidative palladium-catalyzed cross-coupling of pyrimidines containing pyridotriazol-1-yloxy (OPt) as either a urea or an amide functional group with arylboronic acids in the presence of Cs₂CO₃ in DME containing 0.6-1.0% H₂O is described for the preparation of heteroaryl ethers. The bromo substitution in the case of 3-(5-bromo-pyrimidin-2-yloxy)-3H-[1,2,3]triazolo[4,5-b]pyridine could serve as a handle for further elaborations such as Suzuki coupling for attaching varied aryl groups.

Organic 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 C3H5BN2O2, Formula: C3H5BN2O2.

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

Giordanetto, Fabrizio published the artcileDiscovery of phosphoinositide 3-kinases (PI3K) p110β isoform inhibitor 4-[2-hydroxyethyl(1-naphthylmethyl)amino]-6-[(2S)-2-methylmorpholin-4-yl]-1H-pyrimidin-2-one, an effective antithrombotic agent without associated bleeding and insulin resistance, Application of 1H-Pyrazole-4-boronic acid, the publication is Bioorganic & Medicinal Chemistry Letters (2012), 22(21), 6671-6676, database is CAplus and MEDLINE.

Structure-based evolution of the original fragment leads resulted in the identification of 4-[2-hydroxyethyl(1-naphthylmethyl)amino]-6-[(2S)-2-methylmorpholin-4-yl]-1H-pyrimidin-2-one, (S)-21, a potent, selective phosphoinositide 3-kinases (PI3K) p110β isoform inhibitor with favorable in vivo antiplatelet effect. Despite its antiplatelet action, (S)-21 did not significantly increase bleeding time in dogs. Addnl., due to its enhanced selectivity over p110α, (S)-21 did not induce any insulin resistance in rats.

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 C3H5BN2O2, Application of 1H-Pyrazole-4-boronic acid.

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