Month: December 2022

Zhi, Li-Hua published the artcile3-Methyl-1-phenyl-4-[(Z)-phenyl(4-acetamidoanilino)methylidene]-1H-pyrazol-5(4H)-one, COA of Formula: C17H14N2O2, the publication is Acta Crystallographica, Section E: Structure Reports Online (2012), 68(7), o2132, database is CAplus and MEDLINE.

In the title compound, C₂₅H₂₂N₄O₂, the dihedral angles between the central pyrazole ring and the Ph and benzene rings are 37.01(3), 75.58(7) and 49.67(8)°. An intramol. N-H···O H bond generates an S(6) motif. In the crystal, N-H···O H bonds link mols. into a zigzag chain extended along the b axis. Crystallog. data and at. coordinates are given.

Acta Crystallographica, Section E: Structure Reports Online published new progress about 4551-69-3. 4551-69-3 belongs to pyrazoles-derivatives, auxiliary class Benzenes, name is 4-Benzoyl-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one, and the molecular formula is C6H4ClN3S, COA of Formula: C17H14N2O2.

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

Carpenter, Joseph published the artcileUtilization of an Active Site Mutant Receptor for the Identification of Potent and Selective Atypical 5-HT_2C Receptor Agonists, Quality Control of 724710-02-5, the publication is Journal of Medicinal Chemistry (2017), 60(14), 6166-6190, database is CAplus and MEDLINE.

Agonism of the 5-HT_2C receptor represents one of the most well-studied and clin. proven mechanisms for pharmacol. weight reduction Selectivity over the closely related 5-HT_2A and 5-HT_2B receptors is critical as their activation has been shown to lead to undesirable side effects and major safety concerns. In this communication, we report the development of a new screening paradigm that utilizes an active site mutant D134A (D3.32) 5-HT_2C receptor to identify atypical agonist structures. We addnl. report the discovery and optimization of a novel class of nonbasic heterocyclic amide agonists of 5-HT_2C. SAR investigations around the screening hits provided a diverse set of potent agonists at 5-HT_2C with high selectivity over the related 5-HT_2A and 5-HT_2B receptor subtypes. Further optimization through replacement of the amide with a variety of five- and six-membered heterocycles led to the identification of 6-(1-ethyl-3-(quinolin-8-yl)-1H-pyrazol-5-yl)pyridazin-3-amine (69). Oral administration of 69 to rats reduced food intake in an ad libitum feeding model, which could be completely reversed by a selective 5-HT_2C antagonist.

Journal of Medicinal Chemistry 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, Quality Control of 724710-02-5.

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

Gu, Zheng-Song published the artcileSynthesis and antidepressant effect of novel aralkyl piperazine and piperidine derivatives targeting SSRI/5-HT_1A/5-HT₇, Category: pyrazoles-derivatives, the publication is Bioorganic & Medicinal Chemistry Letters (2019), 29(23), 126703, database is CAplus and MEDLINE.

A series of novel aralkyl piperazine and piperidine derivatives were synthesized, and evaluated for their serotonin reuptake inhibitory and 5-HT_1A/5-HT₇ receptors affinities activity. Antidepressant activities in vivo of the selective compound were screened using the forced swimming test (FST) and tail suspension test (TST). The results indicated that compound 19a (I) exhibited high affinities for the 5-HT_1A/5-HT₇ receptors (5-HT_1A, K_i = 12 nM; 5-HT₇, K_i = 3.2 nM) coupled with potent serotonin reuptake inhibition (IC₅₀ = 14 nM) and showed a marked antidepressant-like effect in the FST and TST models.

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

Burdick, Daniel J. published the artcileFragment-based discovery of potent ERK2 pyrrolopyrazine inhibitors, Category: pyrazoles-derivatives, the publication is Bioorganic & Medicinal Chemistry Letters (2015), 25(21), 4728-4732, database is CAplus and MEDLINE.

A fragment-based lead discovery approach was used to discover novel ERK2 inhibitors. The crystal structure of N-benzyl-9H-purin-6-amine (compound 1) in complex with ERK2 elucidated its hinge-binding mode. In addition, the simultaneous binding of an imidazole mol. adjacent to (1) suggested a direction for fragment expansion. Structure-based core hopping applied to (1) led to 5H-pyrrolo[3,2-b]pyrazine that afforded direct vectors to probe the pockets of interest while retaining the essential hinge binding elements. Utilizing the new vectors for SAR exploration, the new core (I) was quickly optimized to 7-(1-benzyl-1H-pyrazol-4-yl)-2-(pyridin-4-yl)-5H-pyrrolo[3,2-b]pyrazine (compound 39) resulting in a greater than 6600-fold improvement in potency.

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

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