Showing papers on "Pyrazole published in 2020"

Synthesis of Metal–Organic Frameworks MIL-101(Cr)-NH2 Containing Phosphorous Acid Functional Groups: Application for the Synthesis of N-Amino-2-pyridone and Pyrano [2,3-c]pyrazole Derivatives via a Cooperative Vinylogous Anomeric-Based Oxidation

Abstract: In the current paper, we successfully developed and used metal-organic frameworks (MOFs) based on MIL-101(Cr)-NH2 with phosphorus acid functional groups MIL-101(Cr)-N(CH2PO3H2)2. The synthesized metal-organic frameworks (MOFs) as a multi-functional heterogeneous and nanoporous catalyst were used for the synthesis of N-amino-2-pyridone and pyrano [2,3-c]pyrazole derivatives via reaction of ethyl cyanoacetate or ethyl acetoacetate, hydrazine hydrate, malononitrile, and various aldehydes. The final step of the reaction mechanism was preceded by a cooperative vinylogous anomeric-based oxidation. Recycle and reusability of the described catalyst MIL-101(Cr)-N(CH2PO3H2)2 were also investigated.

Novel Anticancer Fused Pyrazole Derivatives as EGFR and VEGFR-2 Dual TK Inhibitors.

Abstract: EGFR and VEGFR-2 represent promising targets for cancer treatment as they are very important in tumor development as well as in angiogenesis and metastasis. In this work, 6-amino-4-(2-bromophenyl)-3-methyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile 1 and (E)-4-(2-Bromobenzylidene)-5-methyl-2,4-dihydro-3H-pyrazol-3-one 11 were selected as starting materials to synthesize different fused pyrazole derivatives; dihydropyrano[2,3-c]pyrazole 1, 2, 7-9, and 15, pyrazolo[4',3':5,6]pyrano[2,3-d]pyrimidine 3-6, pyrazolo[3,4-d]pyrimidine 12 and 13, and pyrazolo[3,4-c]pyrazole 14 derivatives were synthesized to evaluate their anticancer activity against HEPG2 human cancer cell lines compared to erlotinib and sorafenib as reference drugs. Seven compounds 1, 2, 4, 8, 11, 12, and 15 showed nearly 10 fold higher activity than erlotinib (10.6 μM) with IC50 ranging from 0.31 to 0.71 μM. In vitro EGFR and VEGFR-2 inhibitory activity were performed for the synthesized compounds, and the results identified compound 3 as the most potent EGFR inhibitor (IC50 = 0.06 μM) and compound 9 as the most potent VEGFR-2 inhibitor (IC50 = 0.22 μM). Moreover, compounds 9 and 12 revealed potent dual EGFR and VEGFR-2 inhibition, and these results were supported by docking studies of these two compounds within the active sites of both enzymes.

Synthesis and herbicidal activity of novel pyrazole aromatic ketone analogs as HPPD inhibitor.

Abstract: Background 4-Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) has been a good target for herbicide discovery. In order to discover novel HPPD herbicides, a series of pyrazole aromatic ketone analogs were designed and synthesized. Results The 25 pyrazole aromatic ketone analogs synthesized were tested for herbicidal activity and compounds A1, A3, A4, A17, A20 and A25 displayed excellent herbicidal activity against Chenopodium serotinum, Stellaria media and Brassica juncea at 37.5 g ha-1 . In addition, compounds A1, A5, A9, A10, A16, A17, A20 and A25 exhibited good crop selectivity for wheat, maize and rice at 150 g ha-1 . Inhibition activities against AtHPPD proved the compounds were HPPD inhibitors. The structure-activity relationship of these pyrazole aromatic ketone analogs was studied using molecular docking. Conclusion These pyrazole aromatic ketone derivatives could be used as lead structures for development of HPPD herbicides against dicotyledonous weeds with further structure modification. © 2019 Society of Chemical Industry.

Discovery of New Schiff Bases Tethered Pyrazole Moiety: Design, Synthesis, Biological Evaluation, and Molecular Docking Study as Dual Targeting DHFR/DNA Gyrase Inhibitors with Immunomodulatory Activity.

Abstract: A series of Bis-pyrazole Schiff bases (6a-d and 7a-d) and mono-pyrazole Schiff bases (8a-d and 9a-d) were designed and synthesized through the reaction of 5-aminopyrazoles 1a-d with aldehydes 2-5 using mild reaction condition with a good yield percentage. The chemical structure of newly formed Schiff bases tethered pyrazole core was confirmed based on spectral and experimental data. All the newly formed pyrazole Schiff bases were evaluated against eight pathogens (Gram-positive, Gram-negative, and fungi). The result exhibited that, most of them have good and broad activities. Among those, only six Schiff bases (6b, 7b, 7c, 8a, 8d, and 9b) displayed MIC values (0.97-62.5 µg/mL) compared to Tetracycline (15.62-62.5 µg/mL) and Amphotericin B (15.62-31.25 µg/mL), MBC values (1.94-87.5 µg/mL) and selectivity to tumor cell than normal cells. Immunomodulatory activities showed that the promising Schiff bases increase the immunomodulator effect of defense cell and the Schiff base 8a is the highest one by (Intra. killing activity = 136.5 ± 0.3%) having a pyrazole moiety as well as amide function (O=C-NH2) and piperidinyl core. Furthermore, the most potent one exhibited broad activity depending on both MIC and MBC values. Moreover, to study the mechanism of these pyrazole Schiff bases, two active Schiff bases 8a and 9b from six derivatives were introduced to study the enzyme assay as dihydrofolate reductase (DHFR) on E. coli organism and DNA gyrase with two different organisms, S. aureus and B. subtilis, to determine the inhibitory activities with lower values in the case of DNA gyrase (8a and 9b) or nearly as DHFR compound 9b, while pyrazole 8a showed excellent inhibitory against all enzyme assay. The molecular docking study against dihydrofolate reductase and DNA gyrase were performed to study the binding between active site in the pocket with the two Schiff bases (8a and 9b) that exhibited good binding affinity with different bond types as H-bonding, aren-aren, and arene-cation interaction as well as study the physicochemical and pharmacokinetic properties of the two active Schiff bases 8a and 9b.

Design, synthesis, molecular modelling and biological evaluation of novel 3-(2-naphthyl)-1-phenyl-1H-pyrazole derivatives as potent antioxidants and 15-Lipoxygenase inhibitors.

Abstract: Oxidative stress is one of the main causes of significant severe diseases. The discovery of new potent antioxidants with high efficiency and low toxicity is a great demand in the field of medicinal...

Multicomponent Pyrazole Synthesis from Alkynes, Nitriles, and Titanium Imido Complexes via Oxidatively Induced N-N Bond Coupling.

Abstract: Pyrazoles are an important class of heterocycles found in a wide range of bioactive compounds and pharmaceuticals. Pyrazole synthesis often requires hydrazine or related reagents where an intact N-N bond is conservatively installed into a pyrazole precursor fragment. Herein, we report the multicomponent oxidative coupling of alkynes, nitriles, and Ti imido complexes for the synthesis of multisubstituted pyrazoles. This modular method avoids potentially hazardous reagents like hydrazine, instead forming the N-N bond in the final step via oxidation-induced coupling on Ti. The mechanism of this transformation has been studied in-depth through stoichiometric reactions of the key diazatitanacyclohexadiene intermediate, which can be accessed via multicomponent coupling of Ti imidos with nitriles and alkynes, ring opening of 2-imino-2H-azirines, or direct metalation of 4-azadiene-1-amine derivatives. The critical transformation in this reaction is the 2-electron oxidation-induced N-N coupling on Ti. This is a rare example of formal N-N coupling on a metal center, which likely occurs through an electrocyclic mechanism analogous to a Nazarov cyclization. Conveniently, these 2-electron-oxidized diazatitanacyclohexadiene intermediates can be accessed via disproportionation of the 1-electron-oxidized species, which allows utilization of weak oxidants such as TEMPO.

Molecular Hybrids Integrated with Benzimidazole and Pyrazole Structural Motifs: Design, Synthesis, Biological Evaluation, and Molecular Docking Studies.

Abstract: Synthesis of a series of benzimidazole-ornamented pyrazoles, 6a–6j has been obtained from arylhydrazine and aralkyl ketones via a multistep synthetic strategy. Among them, a hybrid-possessing para-...

Synthesis and photoluminescence analysis of europium(III) complexes with pyrazole acid and nitrogen containing auxiliary ligands

Abstract: Four red photoluminescent europium(III) complexes have been synthesized by using fluorinated carboxylate ligand, 1-(4-methoxyphenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylic acid as main ligand...

Pyrazole–coumarin and pyrazole–quinoline chalcones as potential antitubercular agents

Abstract: Pyrazole, coumarin, and quinoline are medicinally important moieties. In this study, two series of novel pyrazole-coumarin chalcones and pyrazole-quinoline chalcones were synthesized using multiple-step reactions. All the synthesized compounds were well characterized using different spectroscopic techniques including 1 H and 13 C nuclear magnetic resonance, high-resolution mass spectroscopy, and electrospray ionization-mass spectrometry. The compounds were evaluated for their antitubercular activity against the Mycobacterium tuberculosis H37Rv strain using the microplate Alamar Blue assay, and the minimal inhibitory concentrations (MIC) of the compounds were determined. Among the 32 tested compounds, compounds 3e, 3u, and 7h showed an MIC value of 3.125 µg/ml, and they were found to be nontoxic. Molecular docking studies of the compounds with the enzyme DprE1 revealed the probable mechanism of action. The chalcone derivatives exhibited binding affinity values between -7.047 and -9.353 kcal/mol. ADME parameters were predicted using the QikProp module of the Schrodinger software, and these compounds exhibited good pharmacological and oral absorption properties.

Antitumor effects of novel nickel–hydrazone complexes in lung cancer cells

Abstract: In this work we have synthesized and characterized two new mononuclear nickel(II) complexes [NiLI]·CH3CN (1·CH3CN) and [Ni(H2LII)(NCS)2]·0.5H2O (2·0.5H2O), fabricated from a mixture of Ni(NO3)2 and KNCS with N′,N′′′-(1,2-diphenylethane-1,2-diylidene)di(picolinohydrazide) (H2LI) and 1,2-diphenyl-1,2-bis(((pyridin-2-yl)methylene)hydrazono)ethane (Lig), of which the latter one was transformed in situ into methyl-N-(3,4-diphenyl-5-(pyridin-2-yl)-4,5-dihydro-1H-pyrazol-4-yl)picolinohydrazonate (H2LII) upon coordination to the metal center under synthetic conditions in methanol. The nickel(II) atom in the structure of complex 1 is tetracoordinated and in a N3O geometry, formed by one doubly deprotonated ligand LI, linked through the pyridyl nitrogen atom, one of the amide nitrogen atoms, one of the imine nitrogen atoms and one of the carbonyl oxygen atoms, yielding an almost perfect square-planar coordination environment. The crystal packing of 1·CH3CN is dictated by a set of weak non-covalent interactions, namely C–H⋯O, C–H⋯π and π⋯π stacking interactions. The asymmetric unit of complex 2·0.5H2O contains two crystallographically independent complex molecules [Ni(H2LII)(NCS)2], namely 2-I and 2-II, which are geometrically very similar. The metal atoms are six-coordinated and in a N6 geometry, formed by one neutral ligand H2LII, linked through two pyridyl nitrogen atoms, one amine nitrogen atom from the pyrazole ring, one imidate nitrogen and two NCS− nitrogen atoms, yielding a distorted octahedral coordination environment. The crystal packing of 2·CH3CN is mainly dictated by intermolecular N–H⋯N, N–H⋯S and O–H⋯S hydrogen bonds, yielding a 3D framework, which is further stabilized by intermolecular π⋯π stacking interactions. From the topological point of view, the hydrogen bonded 3D framework of 2·0.5H2O reveals a four-connected uninodal crb/BCT; 4/4/t5; sqc184 topology. In in vitro experiments, both complexes showed dose dependent cytotoxicity and killed A549 lung cancer cells via an apoptotic pathway. Both complexes also reduced the expression of Snail2, leading to an increase in E-cadherin expression and inhibiting the motility of the cells. The complexes were determined as potential antitumor agents.

The Biosynthetic Gene Cluster of Pyrazomycin—A C-Nucleoside Antibiotic with a Rare Pyrazole Moiety

Abstract: Pyrazomycin is a rare C-nucleoside antibiotic containing a naturally occurring pyrazole ring, the biosynthetic origin of which has remained obscure for decades. In this study we report the identification of the gene cluster responsible for pyrazomycin biosynthesis in Streptomyces candidus NRRL 3601, revealing that the StrR-family regulator PyrR is the cluster-situated transcriptional activator governing pyrazomycin biosynthesis. Furthermore, our results from in vivo reconstitution and stable-isotope feeding experiments provide support for the hypothesis that PyrN is a new nitrogen-nitrogen bond-forming enzyme that catalyzes the linkage of the ϵ-NH2 nitrogen atom of l-N6 -OH-lysine and the α-NH2 nitrogen atom of l-glutamic acid. This study lays the foundation for further genetic and biochemical characterization of pyrazomycin pathway enzymes involved in constructing the characteristic pyrazole ring.

Design, synthesis and molecular modelling studies of some pyrazole derivatives as carbonic anhydrase inhibitors

Abstract: In this study, newly synthesised compounds 6, 8, 10 and other compounds (1–5, 7 and 9) and their inhibitory properties against the human isoforms hCA I and hCA II were reported for the first time. ...