In Silico and in Vitro Analysis of Pyrazolone Derivatives against Zika Virus and Identification of Potential NS5 Methyltransferase Inhibitors by Molecular Docking

Zika virus (ZIKV), a mosquito-borne flavivirus, has been associated with benign infections for decades. However, it has become a public health concern due to its association with severe fetal and neurological complications. Although many efforts have been made to control ZIKV infection, approved vaccines or antiviral drugs are still lacking. Consequently, the development of new effective anti-ZIKV agents is urgently needed. In this context, we investigated the antiviral potential of pyrazolone derivatives against ZIKV replication using in silico and in vitro methods. The four pyrazolone derivatives evaluated (1a, 1b, 1c, and 1d) inhibited over 50% of ZIKV replication with low cytotoxicity. Among them, compound 1b exhibited the most potent activity (EC50 = 4.3 μM) and the highest selectivity (SI = 342). Mechanism of action studies indicated that these compounds act at early stages of virus replication, and compound 1b can also directly inactivate ZIKV particles. Molecular docking studies suggested that these compounds can bind to and block the activity of ZIKV NS5 methyltransferase. Finally, pharmacokinetic and toxicological predictions have reinforced the safety and drug-like profiles of these derivatives. In conclusion, the pyrazolone scaffold proved to be valuable for anti-ZIKV drug development, and the derivatives studied deserve further investigation.

Synthesis of Chlorosulfonyl-containing Pyrazolone Azo Compounds with Thionyl Chloride-DMF System

Chlorosulfonyl-containing pyrazolone azo compounds (2a, 2b) have been prepared by reaction of the corresponding sodium sulfonate (1a, 1b) with thionyl chloride in the presence of a catalytic quantity of N,Ndimethylformamide in dry benzene. The effects of reaction temperature, time, catalyst and solvent amount on the yield of 2a and 2b were investigated. The results show that chlorination of 1a and 1b under optimal conditions gives 2a and 2b in 95.5% and 99.2% yield respectively. The given method is facile and suitable for large-scale synthesis.

Synthesis, Crystal Structure and Biological Properties of One Zinc(Ⅱ) Complex Based on 4-Acyl Pyrazolone Derivative

[Zn（L）（CH3OH）3]（H2L = N-（1-phenyl-3-methyl-4-propenylidene-5-pyrazolone）-salicylidene hydrazide） has been synthesized by the reaction of zinc nitrate and ligand H2 L. The complex crystallizes in orthorhombic system, space group Pbca with a = 5.888（15）, b = 14.564（14）, c = 22.20（2） , V = 5137（8） 3, Z = 8 and F（000） = 2184. The ligand serves as a negative bivalent tridentate chelating agent to coordinate with the central zinc（II） atom. DNA-binding was studied by UV-Vis spectral analysis and ethidium bromide（EB） displacement experiments. The results showed that the DNA-binding constant of the complex is 5.1×104 M–1. Antitumor activity of [Zn（L）（CH3OH）3] and the ligand have been investigated by MTT assay, which indicated that the complex has better cytotoxicity to Eca-109 and He La than free ligand.

Study on the Synergistic Extraction of Ytterbium with 1－Phenyl－3－Methyl－4－（α－Furoyl）－5－Pyrazolone and Neutral Extractant

The extraction of Yb3+ by HA [1-phenyl-3-methyl-4-(α-furoyl)-5-pyrazolone] and by HA in combination with a neutral extractant B in toluene have been studied, where B represents n-butyloctyl sulfoxide (BOSO), n-pentylhexyl sulfoxide (PHSO), ethyl-n-dodecyl sulfoxide (EDSO), diphenyl sulfoxide (DPSO) or TBP. The composition of the synergistic extraction complexes have been shown to be YbA3·B and their extraction equilibrium constants have been determined separately.

Synthesis and Crystal Structure of N-(1-Phenyl-3methyl-4-benzal-pyrazolone-5)-furoic Hydrazide

N-(1-Phenyl-3-methyl-4-benzal-pyrazolone-5)-furoic hydrazide (PMBP-FUH, C22H18N4O3, CCDC No: 188946) has been synthesized and characterized by IR spectrum, 1H NMR and single-crystal X-ray diffraction. The crystal is of orthorhombic, space group Pbca with a = 11.870(2), b = 15.951(3), c = 19.674(3) ? V = 3725.0(11) ?, Mr = 386.40, Z = 8, Dc = 1.378 g/cm3, F(000) = 1616, R = 0.0455 and wR = 0.0809. The inter- or intramolecular hydrogen bonds result in the formation of three-dimensional network structure.

Crystal Structure of a Novel Compound: 1-Phenyl-3-ethyl-4-(salicylidene hydrazide)-propenylidene-pyrazolone-5

A novel compound PMPP-SAL （1-phenyl-3-methyl-4-（salicylidene hydrazide）- propenylidene-pyrazolone-5） has been synthesized and characterized by elemental analysis, IR,^1H NMR and single-crystal X-ray diffraction. The X-ray diffraction reveals that the compound is of orthorhombic, space group Pbca with a=16.132（5）, b=10.113（3）, c=23.143（7） A, V=3776（2）A°^3, Z=8, C20H20N4O3, Mr=364.40, Dc =1.282 g/cm^3, F（000）=1536,μ（MoKa）=0.089 mm^-1, S=0.992, R=0.0578 and wR=0.1362 for 1871 observed reflections with I〉2σ（I）. In the crystal, the compound possesses two C=O bonds and exists in the NH-form＇ other than NH-form.

Microwave-assisted Synthesis and Crystal Structure of 3-Acetamido-1-phenyl-4-(2,6-dichloro)benzylidene-5-pyrazolone

The title compound,3-acetamido-1-phenyl-4-（2,6-dichloro）benzylidene-5-pyrazolone（C18H13Cl2N3O2,Mr = 374.21）,has been synthesized by one-step condensation of 2,6-dichloroben-zaldehyde with acetic anhydride and 3-amino-1-phenyl-5-pyrazolone under microwave irradiation.The compound was characterized by means of IR and 1H NMR.Its crystal and molecular structure were determined by X-ray diffractometry.It belongs to the orthorhombic system,space group Pbca,with a = 12.5312（13）,b = 8.5495（9）,c = 31.110（3） ,V = 3332.9（6） 3,Z = 8,Dc = 1.492 g/cm3,λ = 0.71073 ,μ（MoKα） = 0.407 mm-1,F（000） = 1536,the final R = 0.0394 and wR = 0.0984.A total of 15894 reflections were collected,of which 3630 were independent（Rint = 0.0362）.There exist three planes in the molecular structure.X-ray analysis reveals that the dihedral angles between planes 1 and 2,1 and 3 and 3 and 2 are 80.89,74.29 and 20.57°,respectively.

Three novel photoisomeric compounds of the 4-acyl pyrazolone derivants: Crystal structures and substituent effects on photo-isomerism in solid state

Three new photoisomeric compounds: 1,3-diphenyl-4-benzal-5-pyrazolone 4-methylthiosemicarbazone (DPBP-MTSC), 1,3-diphenyl-4-(4′-methylbenzal)-5-pyrazolone 4-methylthiosemicarbazone (DP4MBP- MTSC), and 1,3-diphenyl-4-(4′-bromobenzal)-5-pyrazolone 4-methylthiosemicarbazone (DP4BrBP-MTSC) were synthesized by direct condensation of pyrazolones and 4-methylthiosemicarbazone. Their struc- tures were confirmed using 1H NMR, IR, elemental analyses, and X-ray crystallographic analyses. The photoisomeric properties in the solid state were studied under UV light irradiation and the photo- isomerization phenomena were interpreted by the double proton-transfer mechanism. Moreover, the effects of different substituent groups at the 4-position of the benzal in the three compounds on the photoisomeric properties were discussed.

Asymmetric cooperative catalysis in the conjugate addition of pyrazolones to nitroolefins and subsequent dearomative chlorination

Over the past decade many bifunctional amine-thioureas have been developed as active metal-free organocatalysts. Coopera-tive catalysis of these amino-thioureas allows high reaction rates and excellent transfer of stereocbemical information. Despite these impressive advances, the design of new high-performance catalysts for applications in asymmetric catalytic reactions is of ongoing interest in organic chemistry. Herein we describe a cooperative catalyst system consisting of a chiral amine thiourea and an achiral organic acid that promotes the conjugate addition of 4-nonsubstituted pyrazolones to nitroolefins and subsequent dearomative chlorination. The corresponding adducts and the subsequent products were obtained in high to excel lent yields （up to 99%） and high stereoselectivities （up to 99/1 dr, 98% ee） under mild reacton conditions. These transforma tions provide an easy access to enantio-enriched pvrazole derivatives, which could possess Potential oharmaceutical activity.

Preparation and photochromic properties of pyrazolones/polyvinyl alcohol composite films

Novel photochromic composite films have been successfully fabricated by dispersing pyrazolone derivative：1,3-Diphenyl-4-（3-chlorobenzal）-5-hydroxypyrazole 4-phenylsemicarbazone（la） into hydrosol of polyvinyl alcohol（PVA）.The microstructure,photochromic behaviors and thermal bleaching properties were investigated by Raman spectroscopy,X-ray powder diffraction（XRD）,field emission scanning electron microscopy（FE-SEM） and ultraviolet-visible absorption spectroscopy（UV-vis）.The results showed that la was not only blended but also well dispersed in the PVA polymer films with a suitable content of chromophore.Upon UV light irradiation,the composite films gradually changed from colorless to yellow and recovered fully to the initial state upon thermal bleaching.The time constants of photochromic reactions were almost the same as those of la observed in their crystalline state,indicating that the photochromic phenomenon is barely disturbed by the polymer matrix.

Visible light-promoted enantioselective aerobic oxidation of pyrazolones by phase transfer catalysis

An efficient and enantioselective aerobic oxidation of 4-substituted pyrazolones has been developed by phase transfer catalysis.Using visible light as the driving force and O_(2)(in air)as the oxidant,broad scopes(38 examples)of pyrazolones bearing an oxygen-attached carbon stereocenter at C-4 position were obtained in high yields(up to 98%)and excellent enantioselectivities(up to 93%ee)under mid conditions.The ready availability of catalyst,ease of operation,and low-cost and eco-friendly nature highlighted the practical utility of this visible lightpromoted enantioselective aerobic oxidation.

Photoluminescent and Electroluminescent Properties of Ligand Emitting Y^(3+), La^(3+), Gd^(3+) and Lu^(3+) Complexes

The photoluminescent (PL) and electroluminescent (EL) properties of a series of ligand emitting rare earth complexes (including Y^(3+), La^(3+), Gd^(3+) and Lu^(3+)) were systematically studied. These complexes have the same anionic ligand, 1-phenyl-3-methyl-4-isobutyryl-5-pyrazoloneate (PMIP), and three neutral ligands, triphenyl phosphine oxide (TPPO), 2, 2′-dipyridine (Bipy) and phenanthroline (Phen). Measured with 60 nm thin film of these complexes vaporized in vacuum on quartz substrates, a good regularity in the PL properties was observed. For rational comparison, the same structural EL devices based on these complexes, ITO/PVK (40 nm)/the complex (80 nm)/Mg: Ag (200 nm)/Ag (100 nm), were fabricated. Excluding the exciplex emission happens, the EL luminance usually increases with the increasing of PL efficiency.

Studies on Extraction Behaviour of Cobalt(II) with Nitrobenzoylprazolone-5

The extraction of Cobalt(II) from aqueous solution using 1-phenyl-3-methyl-4-(p-nitrobenzoyl)pyrazolone (HPMNP) in various organic solvents was studied as a function of pH and extractant concentration. Extraction into organic chloroform phase was more efficient than with any other solvent. The extraction equilibrium constant was found to be log Kex= -7.04. Optimum conditions for extraction of Co(II) exist at pH of between 5.5 and 7.0, ionic strength of 0.3 Mand constant extractant concentration of 0.02 M. Shaking the organic Co(II) chelate complex with 0.2 Macid strips the Co(II) ions into the aqueous phase. It was established that Co(II) complex extracted is of composition, Co(PMNP)2.

An Eco-Friendly Synthesis of Heterocyclic Moieties Condensed with Pyrazole System under Green Conditions and Their Biological Activity

The efficient, facile and green synthesis of 4-bromo pyrazolone by using N-bromo saccharine as valuable green reagent encouraged us to prepare some new fused heterocycles as furopyrazole, pyranopyrazole, imidazopyrazole, pyrazolothiazole, pyrazol thiazolopyrimidine, pyrazolothiazine, oxathinopyrazole, pyrazolobenzooxazine, and pyrazoloquinoxaline. The synthesis was carried out by a basic condensation of bromo pyrazolone 2 and a suitable reagent in a one-pot reaction using chitosan as a green basic catalyst. The reactions were carried out by microwave irradiation technique as a green source of energy as well as the conventional heating. The antioxidant activity of the prepared compounds was studied using 1,1-phenyl-2-picrylhydrazyl (DPPH) assay and their antibacterial activity against Gram-positive, Gram-negative bacteria and antifungal activity was evaluated.

Remote stereocontrol in the(4+2)cycloadditions of 1,7-zwitterions:Asymmetric synthesis of multifunctionalized tetrahydroquinoline derivatives

The scope of stereochemistry recognition usually occurs near the chiral scaffold of a ligand or catalyst.Remote stereocontrol,which can surpass the limits of stereorecognition of remote prochiral centers,has long been a challenging object of great interest in asymmetric catalysis.The current work realized the remote stereocontrol of 1,7-zwitterion intermediates formed from Huang's o-amino aryl MBH carbonates.With simple and easily accessibleβ-ICD as the bifunctional catalyst,multifunctionalized tetrahydroquinoline derivatives could be synthesized via(4+2)cycloadditions with excellent enantioselectivity and diastereoselectivity under mild conditions.The strategy possesses broad substrate scope,and three types of electron-deficient enones are successfully applied.Mechanistic studies disclosed the Lewis base-catalyzed reaction pathway,and H-bonding between the catalyst and enones is crucial for long-range stereocontrol.Scale-up reaction and transformations of the tetrahydroquinoline products demonstrated the potential of this strategy.

Synthesis,spectroscopic properties and applications of novel N-heterocycle-containing benzotriazoles as UV absorbers

Two novel N-heterocycle-containing benzotriazole compounds, 5-（5-chloro-2-benzotriazolyl）-6-hydroxy-l,4-dimethyl-3-car- bonitrile-2-pyddone （2） and 4-（5-chloro-2-benzotdazolyl）-5-methyl-2-phenyl-3-pyrazolone （4）, were synthesized from reactant 4- chloro-2-nitroaniline via diazotization, azo coupling, reductive cyclization and acidification. Their structures were confirmed by Fr-IR, 1H NMR, mass spectroscopy and elemental analysis. Their spectral properties were investigated and compared with that of a common commercial benzotriazole UV absorber Tinuvin 326. It is found that the novel N-heterocycle-containing benzotriazole compounds exhibit sharp single peak in the range of 280-400 nm and have much higher molar extinction coefficients than that of Tinuvin 326. Their anti-UV protection properties on polyester fabric were also evaluated and compound 4 was much superior to compound 2 due to its higher exhaustion.

A novel solid state Michael addition reaction of N-heterocyclic compounds containing active C-H bond

In this paper, a novel solid state Michael-type addition reaction of N-heterocyclic compounds containing the active-CH group was investigated. 3-Methyl-1-phenyl-5-pyrazolone (MPP) and indole (In) reacted with 4-arylmethylene-3-methyl-1-phenyl-5-pyrazolone (1) in the solid state at room temperature to give the corresponding adducts, aryl-4,4'-bis(5-hydroxy-3-methyl-1-phenyl-pyrazolyl) methane (2a-n) and 1-aryl-1-(5'-hydroxy-3'-methyl-1'-phenyl-4'-pyrazolyl)-1-(3 ''-indolyl) methane (3a-n), respectively. This is a feasible method for preparing the compound which contains two heterocyclic groups on the same carbon.

Synthesis, characterization and extended X-ray absorption fine structure of novel polynuclear copper complexes with new eighteen-membered macrocycle ligands

Macrocycle compounds have great importance in host-guest chemistry and moleculeidentifications. 4-acetyl-bispyrazolones are a new type of polydentate ligands. Whenthey react with diamine compounds, new compounds or complexes containing C=O andC=N groups can be obtained. These compounds can be used to study the relationship ofcoordination structure and its properties, energy transferring processes between metal

A Novel Photochemical Reaction of 4-Bromo-3-methyl-1-phenyl-4,5-dihydro-pyrazol-5-one

UV-Irradiation of 4-bromo-3-methyl-1-phenyl-4,5-dihydro-pyrazol-5-one (1) in the presence of various aromatic hydrocarbons gave different types of photoproducts; depending on the nature of the hydrocarbons via an electron-transfer mechanism. In the presence of naphthalene or phenanthrene a photochemical homocoupling reaction of I occurred to form 2 or 2 and 3, respectively.