Day: November 21, 2022

Otrubova, Katerina published the artcileN-Acyl pyrazoles: Effective and tunable inhibitors of serine hydrolases, Recommanded Product: 1H-Pyrazole-1-carbonyl chloride, the publication is Bioorganic & Medicinal Chemistry (2019), 27(8), 1693-1703, database is CAplus and MEDLINE.

A series of N-acyl pyrazoles was examined as candidate serine hydrolase inhibitors in which the active site acylating reactivity and the leaving group ability of the pyrazole could be tuned not only through the nature of the acyl group (reactivity: amide > carbamate > urea), but also through pyrazole C4 substitution with electron-withdrawing or electron-donating substituents. Their impact on enzyme inhibitory activity displayed pronounced effects with the activity improving substantially as one alters both the nature of the reacting carbonyl group (urea > carbamate > amide) and the pyrazole C4 substituent (CN > H > Me). It was further demonstrated that the acyl chain of the N-acyl pyrazole ureas can be used to tailor the potency and selectivity of the inhibitor class to a targeted serine hydrolase. Thus, elaboration of the acyl chain of pyrazole-based ureas provided remarkably potent, irreversible inhibitors of fatty acid amide hydrolase (FAAH, apparent K_i = 100-200 pM), dual inhibitors of FAAH and monoacylglycerol hydrolase (MGLL), or selective inhibitors of MGLL (IC₅₀ = 10-20 nM) while simultaneously minimizing off-target activity (e.g., ABHD6 and KIAA1363).

Bioorganic & Medicinal Chemistry published new progress about 53355-55-8. 53355-55-8 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Chloride,acyl chloride,Amide, name is 1H-Pyrazole-1-carbonyl chloride, and the molecular formula is C4H3ClN2O, Recommanded Product: 1H-Pyrazole-1-carbonyl chloride.

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

Patil, Dayanand published the artcileNovel crown ether functionalized imidazolium-based acidic ionic liquid catalyzed synthesis of pyrazole derivatives under solvent-free conditions, Related Products of pyrazoles-derivatives, the publication is Research on Chemical Intermediates (2015), 41(9), 6843-6858, database is CAplus.

An innovative designed novel crown ether functionalized imidazolium-based reusable acidic ionic liquid [crown ether MIm] [HSO₄] has been efficiently implemented for the synthesis of pyrazole derivatives using various substituted enaminones, hydrazine hydrate and Ph hydrazine under solvent-free conditions. Structural novelty and task efficiency of the catalyst, high yields of desired products, greener approach attributing high atom economy (green chem. method) and solvent-free conditions render this protocol suitable to cope with the current demand in contemporary organic chem. The inventive idea of utilizing crown ether functionalized ionic liquid as a catalyst was for the first time demonstrated in this protocol. The synthesis of the target compounds was achieved using [6-[1,4,7,10,13-benzopentaoxacyclopentadecin-15-yl]hexyl]imidazolium sulfate as a catalyst. Starting materials included hydrazine, phenylhydrazine and enaminone derivatives [(amino)alkenone derivatives] such as 3-(dimethylamino)-1-phenyl-2-propen-2-one, 3-(dimethylamino)-1-(2-furanyl)-2-propen -1-one, 2-[(dimethylamino)methylene]-1,3-cyclohexanedione. The title compounds thus formed included pyrazole derivatives and analogs, such as 3-phenyl-1H-pyrazole, 3-(2-furanyl)-1H-pyrazole, 1,5,6,7-tetrahydro-4H-indazol-4-one (indazole derivatives).

Research on Chemical Intermediates 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, Related Products of pyrazoles-derivatives.

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

Szymanska, Ewa published the artcileAryl- and heteroaryl-substituted phenylalanines as AMPA receptor ligands, Computed Properties of 763120-58-7, the publication is Chemical Biology & Drug Design (2017), 90(6), 1271-1281, database is CAplus and MEDLINE.

A series of racemic unnatural amino acids was rationally designed on the basis of recently published X-ray structures of the GluA2 LBD with bound phenylalanine-based antagonists. Twelve new diaryl- or aryl/heteroaryl-substituted phenylalanine derivatives were synthesized and evaluated in vitro in radioligand binding assays at native rat ionotropic glutamate receptors. The most interesting compound in this series, (RS)-2-amino-3-(3′-hydroxy-5-(1H-pyrazol-4-yl)-[1,1′-biphenyl]-3-yl)propanoic acid 7e, showed the binding affinity of 4.6 μM for native AMPA receptors and over fourfold lower affinity for kainic acid receptors. Furthermore, 7e was evaluated at recombinant homomeric rat GluA2 and GluA3 receptors. Recently reported X-ray structures 5CBR and 5CBS, representing two distinct antagonist binding modes, were used as templates for mol. docking of the synthesized series. Binding data supported with mol. modeling confirmed that aryl/heteroaryl-substituted phenylalanine analogs effectively bind to AMPA receptors with low micromolar affinity and high selectivity over native NMDA and kainate receptors. These properties make 7e a promising lead for the further development of new AMPA receptor ligands.

Chemical Biology & Drug Design 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 C14H28O5S, Computed Properties of 763120-58-7.

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

Barlaam, Bernard published the artcileDiscovery of AZD4573, a Potent and Selective Inhibitor of CDK9 That Enables Short Duration of Target Engagement for the Treatment of Hematological Malignancies, Application In Synthesis of 2057507-56-7, the publication is Journal of Medicinal Chemistry (2020), 63(24), 15564-15590, database is CAplus and MEDLINE.

A CDK9 inhibitor having short target engagement would enable a reduction of Mcl-1 activity, resulting in apoptosis in cancer cells dependent on Mcl-1 for survival. We report the optimization of a series of amidopyridines (from compound 2), focusing on properties suitable for achieving short target engagement after i.v. administration. By increasing potency and human metabolic clearance, we identified compound 24, a potent and selective CDK9 inhibitor with suitable predicted human pharmacokinetic properties to deliver transient inhibition of CDK9. Furthermore, the solubility of 24 was considered adequate to allow i.v. formulation at the anticipated ED. Short-term treatment with compound 24 led to a rapid dose- and time-dependent decrease of pSer2-RNAP2 and Mcl-1, resulting in cell apoptosis in multiple hematol. cancer cell lines. Intermittent dosing of compound 24 demonstrated efficacy in xenograft models derived from multiple hematol. tumors. Compound 24 is currently in clin. trials for the treatment of hematol. malignancies.

Journal of Medicinal Chemistry published new progress about 2057507-56-7. 2057507-56-7 belongs to pyrazoles-derivatives, auxiliary class Pyrazoles, name is 3-Bromo-5,5-dimethyl-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazole, and the molecular formula is C8H11BrN2, Application In Synthesis of 2057507-56-7.

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

Hu, Liming published the artcileDesign, synthesis, and biological activity of 4-(imidazo[1,2-b]pyridazin-3-yl)-1H-pyrazol-1-yl-phenylbenzamide derivatives as BCR-ABL kinase inhibitors, HPLC of Formula: 1416437-27-8, the publication is Bioorganic & Medicinal Chemistry Letters (2016), 26(23), 5830-5835, database is CAplus and MEDLINE.

A series of 4-((pyrazolo[1,5-a]pyrimidin-6-yl)-1H-pyrazol-1-yl)phenyl-3-benzamide derivatives and 4-((imidazo[1,2-b]pyridazin-3-yl)-1H-pyrazol-1-yl)phenyl-3-benzamide derivatives were designed, synthesized as new BCR-ABL tyrosine kinase inhibitors by using combinational strategies of scaffold hopping and conformational constraint. These new compounds were screened for BCR-ABL1 kinase inhibitory activity, and most showed good inhibitory activity against BCR-ABL1 kinase. One of the most potent compounds I strongly suppressed BCR-ABL1 kinase with IC₅₀ value of 8.5 nM. The tested compounds I (and a second compound) showed strong inhibitory activities against K562 with IC₅₀ value of less than 2 nM. Mol. docking studies indicated that these compounds fitted well with the active site of BCR-ABL1 protein. The results showed these inhibitors may serve as lead compounds for developing new drugs targeted at BCR-ABL kinase.

Bioorganic & Medicinal Chemistry Letters published new progress about 1416437-27-8. 1416437-27-8 belongs to pyrazoles-derivatives, auxiliary class Other Aromatic Heterocyclic,Boronic acid and ester,Boronate Esters,Boronic acid and ester, name is 6-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazolo[1,5-a]pyrimidine, and the molecular formula is C12H16BN3O2, HPLC of Formula: 1416437-27-8.

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

Molander, Gary A. published the artcileScope of the Suzuki-Miyaura Cross-Coupling Reactions of Potassium Heteroaryltrifluoroborates, SDS of cas: 763120-58-7, the publication is Journal of Organic Chemistry (2009), 74(3), 973-980, database is CAplus and MEDLINE.

A wide variety of bench-stable potassium heteroaryltrifluoroborates were prepared, and general reaction conditions were developed for their cross-coupling to aryl and heteroaryl halides. The cross-coupled products were obtained in good to excellent yields. This method represents an efficient and facile installation of heterocyclic building blocks onto preexisting organic substructures.

Journal of Organic 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, SDS of cas: 763120-58-7.

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

Molander, Gary A. published the artcileScope of the Suzuki-Miyaura Cross-Coupling Reactions of Potassium Heteroaryltrifluoroborates, Related Products of pyrazoles-derivatives, the publication is Journal of Organic Chemistry (2009), 74(3), 973-980, database is CAplus and MEDLINE.

A wide variety of bench-stable potassium heteroaryltrifluoroborates were prepared, and general reaction conditions were developed for their cross-coupling to aryl and heteroaryl halides. The cross-coupled products were obtained in good to excellent yields. This method represents an efficient and facile installation of heterocyclic building blocks onto preexisting organic substructures.

Journal of Organic 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, Related Products of pyrazoles-derivatives.

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

Hidalgo, William published the artcile4-Phenylphenalenones as a template for new photodynamic compounds against Mycosphaerella fijiensis, Synthetic Route of 763120-58-7, the publication is Pest Management Science (2016), 72(4), 796-800, database is CAplus and MEDLINE.

Evaluation of 4-phenylphenalenones and structural analogs against the fungal pathogen Mycosphaerella fijiensis (causal agent of black sigatoka disease in bananas) under light-controlled conditions uncovered some key structural features for the design of photodynamic compounds Structure-activity relationship anal. revealed the importance of a chromophoric aryl-ketone and a steroidomimetic structural motif in the activity of the assayed compounds The results pointed to 1,2-dihydro-3H-naphtho[2′,1′:3,4]cyclohepta[1,2-b]furan-3-one, which displayed an activity in the range of propiconazole but with photodynamic behavior. The present work demonstrates that 1,2-dihydro-3H-naphtho[2′,1′:3,4]cyclohepta[1,2-b]heterocyclic-3-one derivatives can be used as potential lead compounds for the development of fungicides, relying on a dual mode of action.

Pest Management Science 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, Synthetic Route of 763120-58-7.

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

Anderson, Niall A. published the artcileSynthesis and determination of absolute configuration of a non-peptidic α_vβ₆ integrin antagonist for the treatment of idiopathic pulmonary fibrosis, Safety of 3-(3,5-Dimethyl-1H-pyrazol-1-yl)phenylboronic acid, the publication is Organic & Biomolecular Chemistry (2016), 14(25), 5992-6009, database is CAplus and MEDLINE.

A diastereoselective synthesis of I, a potential therapeutic agent for the treatment of idiopathic pulmonary fibrosis, which is currently undergoing Phase I trials is reported. The key steps in the synthesis involved alkylation of 2-methylnaphthyridine with (R)-N-Boc-3-(iodomethyl)-pyrrolidine, and an asym. Rh-catalyzed addition of an arylboronic acid to a 4-(N-pyrrolidinyl)crotonate ester. The overall yield of the seven linear step synthesis is 8% and the product is obtained in <99.5% ee proceeding with 80% de. The absolute configuration of I is established by an alternative asym. synthesis involving alkylation of an arylacetic acid using Evans oxazolidinone chem., acylation using the resulting 2-arylsuccinic acid, and reduction The absolute configuration of the benzylic asym. center is established as (S).

Organic & Biomolecular Chemistry published new progress about 1025735-46-9. 1025735-46-9 belongs to pyrazoles-derivatives, auxiliary class Pyrazole,Boronic acid and ester,Benzene,Boronic Acids, name is 3-(3,5-Dimethyl-1H-pyrazol-1-yl)phenylboronic acid, and the molecular formula is C11H13BN2O2, Safety of 3-(3,5-Dimethyl-1H-pyrazol-1-yl)phenylboronic acid.

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

Li, Xiao-jing published the artcileCu(II) and Zn(II) complexes with an acylhydrazone derived from 4-methyl salicylic hydrazide and PMBP: crystal structures and fluorescence properties of Zn(II) complex, Name: 4-Benzoyl-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one, the publication is Wuji Huaxue Xuebao (2015), 31(8), 1661-1666, database is CAplus.

Two complexes [(Cu)(L)(Cl)]·0.5EtOH·1.5H₂O and {[Zn(L)(NO₃)]·2CH₃CN}_n (HL was the acylhydrazone ligand derived from 1-phenyl-3-methyl-4-benzoyl-5-pyrazolone (PMBP) and 4-Me salicylic hydrazide) had been synthesized and characterized by single-crystal X-ray diffraction, elemental anal. and IR spectroscopy. X-ray diffraction anal. results showed that the coordination geometry of the Cu(II) ion in 1 was a distorted square planar geometry with nitrogen and two oxygen atoms provided by the enolizated ligand L^-1 and one chloride anion. However, in complex 2, the Zn(II) ion with a distorted trigonal biyramid coordination geometry was five-coordinated, involving one nitrate anion, one NO₂ donor set of an enolizated ligand L^– and one pyrazoline nitrogen atom from another adjacent acylhydrazone ligand, thus forming one dimension chain-like framework along b axis. When excited at 310 nm, complex 2 exhibited two strong emissions at 434 and 459 nm, while the ligand showed relatively weak emission at 521 nm. In addition, luminescent decay data showed that the mean lifetime (τ) were 7.3528 and 7.7556 μs for HL and complex 2, resp. CCDC: 1058420, HL·0.5EtOH; 1058421, 1; 1058422, 2.

Wuji Huaxue Xuebao 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 C17H14N2O2, Name: 4-Benzoyl-5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one.

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