1453-58-3Relevant academic research and scientific papers
Discovery and SAR Evolution of Pyrazole Azabicyclo[3.2.1]octane Sulfonamides as a Novel Class of Non-CovalentN-Acylethanolamine-Hydrolyzing Acid Amidase (NAAA) Inhibitors for Oral Administration
Armirotti, Andrea,Bandiera, Tiziano,Berti, Francesco,Bertorelli, Rosalia,Bertozzi, Fabio,Bertozzi, Sine Mandrup,Bottegoni, Giovanni,Carbone, Anna,Di Fruscia, Paolo,Fiasella, Annalisa,Giacomina, Francesca,Mengatto, Luisa,Nuzzi, Andrea,Ortega, Jose Antonio,Pagliuca, Chiara,Penna, Ilaria,Pizzirani, Daniela,Ponzano, Stefano,Reggiani, Angelo,Romeo, Elisa,Russo, Debora,Summa, Maria,Tarozzo, Glauco,Giampà, Roberta
, p. 13327 - 13355 (2021/09/20)
Inhibition of intracellularN-acylethanolamine-hydrolyzing acid amidase (NAAA) activity is a promising approach to manage the inflammatory response under disabling conditions. In fact, NAAA inhibition preserves endogenous palmitoylethanolamide (PEA) from degradation, thus increasing and prolonging its anti-inflammatory and analgesic efficacy at the inflamed site. In the present work, we report the identification of a potent, systemically available, novel class of NAAA inhibitors, featuring a pyrazole azabicyclo[3.2.1]octane structural core. After an initial screening campaign, a careful structure-activity relationship study led to the discovery ofendo-ethoxymethyl-pyrazinyloxy-8-azabicyclo[3.2.1]octane-pyrazole sulfonamide50(ARN19689), which was found to inhibit human NAAA in the low nanomolar range (IC50= 0.042 μM) with a non-covalent mechanism of action. In light of its favorable biochemical, in vitro and in vivo drug-like profile, sulfonamide50could be regarded as a promising pharmacological tool to be further investigated in the field of inflammatory conditions.
Ruthenium-catalyzed formation of pyrazoles or 3-hydroxynitriles from propargyl alcohols and hydrazines
Kaufmann, Julia,J?ckel, Elisabeth,Haak, Edgar
supporting information, p. 91 - 101 (2019/07/09)
Functionalized pyrazoles are generated from secondary propragyl alcohols and hydrazines in a ruthenium-catalyzed cascade process, consisting of redox isomerization, Michael addition, cyclocondensation and dehydrogenation steps. The same bifunctional catalyst mediates the conversion of tertiary propargyl alcohols with hydrazine to 3-hydroxynitriles via anti-Markovnikov hydroamination followed by elimination of ammonia.
A practical and highly efficient reductive dehalogenation of aryl halides using heterogeneous Pd/AlO(OH) nanoparticles and sodium borohydride
Kara, Belguzar Yasemin,Yazici, Melike,Kilbas, Benan,Goksu, Haydar
, p. 5898 - 5902 (2016/09/07)
The reductive dehalogenation of aryl halides was performed by using commercially available aluminium oxy-hydroxide-supported palladium (Pd/AlO(OH)) nanoparticles of about 3?nm size (0.5?wt.?% Pd) with sodium borohydride. The dehalogenated products were obtained with absolute conversion in a mixture of H2O/MeOH (v/v=1/1) under ultrasonic conditions at room temperature. All aryl halides were successfully converted to halogen-free compounds within 1.5–4?h with yields of over 95%. The one-pot catalytic method is presented as a new process for the reductive dehalogenation of halogenated compounds. This method is quite simple, highly efficient and eco-friendly, and has an exceptional recovery rate.
Chalcogenation of 1,4-dichlorobut-2-yne with organic dichalcogenides in the system hydrazine hydrate–KOH
Levanova,Vakhrina,Grabel’nykh,Rozentsveig,Russavskaya,Albanov,Klyba,Korchevin
, p. 2083 - 2089 (2016/10/03)
A reaction of organic dichalcogenides R2Y2 (R = Ph, Bn, Pr; Y = S, Se) with 1,4-dichlorobut-2-yne in the system hydrazine hydrate–KOH leads to four principal products: 1,4-bis(organylchalcogenyl)but-2-ynes, 1-organylchalcogenylbut-1-en-3-ynes, 4-organylchalcogenylbut-1-en-3-ynes, and 3(5)-methylpyrazole. The selectivity of the formation of individual products is determined by the ratio of the substrates used and the reaction temperature. A plausible mechanism of chalcogenation considered in the work agrees with the effect of the nature of chalcogene atoms and organic substituents R on stability of intermediates and products. The stabilization of carbanions by α chalcogene-containing groups corresponds to the following order: PhS > PhSe > BnS > BnSe > PrS.
Nitrogen-containing heterocycles from metal β-diketonates
Svistunova,Shapkin,Nikolaeva,Apanasenko
experimental part, p. 756 - 761 (2011/08/06)
Factors determining the reaction of metal β-diketonates with hydrazine, in particular the nature of central metal ion and structure of β-diketonate ligand, are discussed. The possibility for the preparation of other heterocyclic compounds via reaction of metal acetylacetonates with phenylhydrazine, o-phenylenediamine, urea, and thiourea was studied.
Two-stage sonogashira coupling method in the synthesis of auxin active acetylenes
Wayne Craig,Eberle, Martin,Irminger, Bruno,Schueckenboehmer, Anegret,Laime, Yvette,Mueller, Patrick
, p. 1967 - 1974 (2008/09/16)
A sequential Sonogashira coupling of a protected acetylene precursor with aryl halides (5) followed by pyrazolyl iodides (14) allows efficient access to the unsymmetrical aryl-heteroarylacetylene (8). Subsequent regioselective lithiation exchange followed by dimethyl oxalate quench produced readily vicinal ketoesters (9) which show auxin effects in a wide variety of plant species.
N-benzoylpyrazoles are novel small-molecule inhibitors of human neutrophil elastase
Schepetkin, Igor A.,Khlebnikov, Andrei I.,Quinn, Mark T.
, p. 4928 - 4938 (2008/03/13)
Human neutrophil elastase (NE) plays an important role in the pathogenesis of pulmonary disease. Using high-throughput chemolibrary screening, we identified 10 N-benzoylpyrazole derivatives that were potent NE inhibitors. Nine additional NE inhibitors were identified through further screening of N-benzoylpyrazole analogues. Evaluation of inhibitory activity against a range of proteases showed high specificity for NE, although several derivatives were also potent inhibitors of chymotrypsin. Analysis of reaction kinetics and inhibitor stability revealed that N-benzoylpyrazoles were pseudoirreversible competitive inhibitors of NE. Structure-activity relationship (SAR) analysis demonstrated that modification of N-benzoylpyrazole ring substituents modulated enzyme selectivity and potency. Furthermore, molecular modeling of the binding of selected active and inactive compounds to the NE active site revealed that active compounds fit well into the catalytic site, whereas inactive derivatives contained substituents or conformations that hindered binding or accessibility to the catalytic residues. Thus, N-benzoylpyrazole derivatives represent novel structural templates that can be utilized for further development of efficacious NE inhibitors.
Flash vacuum pyrolysis over solid catalysts. 1. Pyrazoles over zeolitest
Moyano,Yranzo
, p. 2943 - 2947 (2007/10/03)
Flash vacuum pyrolysis (fvp) reactions of 1H-pyrazole (1), 3,5-dimethylpyrazole (2), and 3,5-diphenylpyrazole (3) were carried out over zeolites. Reactions were performed using ZCOY-7, NH4-Y, and Na-Y zeolites. Reaction temperatures of heterogeneous reactions were lower than the corresponding temperatures in the homogeneous system, showing a catalytic effect of the zeolites. Compounds 1-3 afforded nitrogen extrusion in homogeneous fvp reactions while in the heterogeneous ones different reactions were present. Compounds 1 and 2 also afforded nitrogen extrusion; products arising from ring fragmentation were found in reactions of 2 and 3 while an isomeric imidazole was isolated in reactions of 3. Isomerization of 3 is attributed to a transition-state selectivity by the catalyst due to the relation between the size of the molecule and the cavity of the zeolite. This isomerization reaction was present only when zeolites with active Broensted sites were used.
Use of low-volatility pyrazole derivatives having hydrophilic groups as nitrification inhibitors
-
, (2008/06/13)
The present invention provides pyrazole compounds which are useful as nitrification inhibitors.
