Pyrazole Moiety Research Articles

Synthesis and antimicrobial screening of novel 2-thiopyrimidine derivatives bearing a pyrazole moiety

Synthesis and antimicrobial screening of novel 2-thiopyrimidine derivatives bearing a pyrazole moiety

A green approach for dyeing cotton fabrics using synthesized reactive disperse dyes and their mixtures under supercritical CO2 medium.

Dyeing natural fabrics using supercritical carbon dioxide is challenging, especially without essential color hues. This work demonstrated that two newly developed reactive disperse dyes with distinct colors and shades were generated, one of which featured from the anthraquinone family and the other yellow, containing a pyrazole moiety. These new dyes and their combinations were used to dye cotton fabric using supercritical carbon dioxide and the highest K/S values were achieved at 8.73 for the mixture of (blue dye: yellow dye 80:20), however the lowest K/S was observed at 7.71 for (blue dye: yellow dye 20:80). The new dyes' chemical compositions were identified using elemental and spectroscopic analyses. The effectiveness of these dyes and their mixtures for cotton dyeing was discussed. The dyed samples were tested for color fastness, and the results indicated that they had excellent color retention and were highly durable in washing. The increasing patterns in both dyeing rate and build-up curves show good compatibility. Furthermore, desirable shades of green can be achieved by mixing blue and yellow dyes at various ratios in supercritical CO2. The compatibility test involves calculating color difference index values for dyed cotton fabrics by utilizing various ratios of a binary mixture of dyes. Furthermore, the dyes under study and dyed samples displayed superior antibacterial properties against gram-positive and gram-negative bacteria compared to certain antibiotics used as a control. These results aligned with the quality and eco-friendly standards required by the industry without the use of water.

Synthesis of novel meta-diamide compounds containing pyrazole moiety and their insecticidal evaluation

Abstract A novel series of meta-diamide compounds incorporating a pyrazole moiety (2a–2v) were designed and synthesized based on cyproflanilide. Their structures were validated through 1H NMR, 13C NMR, and HRMS analyses. These compounds were evaluated for their insecticidal activity against Plutella xylostella, Mythimna separate, Tetranychus cinnabarinus, and Nilaparvata lugens. Most of the title compounds exhibited good activity against N. lugens at 400 mg/L. Compound 2k demonstrated potential for further optimization as an insecticidal lead, thereby extending the application of meta-diamide compounds in the field of sucking mouthparts.

Photoinduced Self-assembly: An Alternative Strategy for the Construction of Coordination Oligomers and Polymers.

Self-assembled oligonuclear and polynuclear complexes have numerous functionalities and potential applications. Generally, such compounds have been constructed by thermal substitution reactions with bridging ligands. Herein, we report bottom-up and photochemical construction of functional coordination oligomers and polymers by photosubstitution-induced self-assembly. The photosubstitution reactions of a ruthenium precursor complex with bridging ligands having pyrazole moieties afford mono-, di-, tri-, tetra-, and pentanuclear ruthenium complexes, Ru1-Ru5, which have one-dimensional architectures. Intramolecular hydrogen bonding between each bridging ligand is a key to construct the molecular nanowires. All the complexes have been isolated and thoroughly characterized. The photochemically synthesized ruthenium complexes act as synthons for longer metal-complex-based nanowires with a length of the order of tens-of nanometers. The multinuclear complexes are generated by photoinduced self-assembly in the presence of a base, and they undergo photoinduced disassembly in the presence of acid.

From Proline to Chlorantraniliprole Mimics: Computer-Aided Design, Simple Preparation, and Excellent Insecticidal Profiles.

Chlorantraniliprole (CHL), a favored agricultural insecticide, is renowned for its high efficiency and broad-spectrum effectiveness against lepidoptera insects. However, the urgency for new insecticide development is underscored by the intricate multistep preparation process and modest overall yields of CHL, along with the escalating challenge of insect resistance. In response, we have crafted CHL mimics from proline employing computer-aided drug design. Molecular docking analysis of CHL's interactions with the ryanodine receptor (RyR) revealed that the nitrogen atom within the pyrazole moiety does not engage in pivotal interactions. Its removal may not abolish bioactivity entirely but could substantially simplify the synthetic process, thereby enhancing atom economy. This revelation prompted the exclusion of nitrogen and the subsequent formation of a pyrrole ring, enabling the meticulous design of synthetic pathways characterized by cost-effective precursors, streamlined synthesis, the avoidance of toxic reagents, minimal instrumentation, and high yields in the pursuit of innovative RyR modulators. Among these modulators, A1 and B1, obtained with yields exceeding 60%, showcased exceptional insecticidal potency, with LC50 values spanning from 0.12 to 1.47 mg L-1 against P. xylostella and M. separate. The inhibitory effects of these two compounds on insect detoxification enzymes imply a reduced likelihood of eliciting resistance in comparison to CHL, a finding further corroborated by their insecticidal potency against resistant pests. Moreover, molecular docking, MD simulations, and DFT calculations provided valuable structural insights, potentially unraveling the superior insecticidal activity of these two molecules, and thus paving the way for developing more potent insecticides.

Synthesis, spectroscopic characterization, antimicrobial activity, and computational studies of five and/or six heterocyclic nitrogen rings linked to thienopyrazole moiety

A new series of thienopyrazoles linked to five and/or six heterocyclic nitrogen rings such as pyrazole, triazole-3-thione, oxadiazole, thiazole-2-thione and/or pyrimidone moieties was synthesized starting from 5-amino-1,3-diphenyl-1H-thieno[3,2-c]pyrazole-6-carboxylic acid hydrazide as a key precursor. For the synthesis of new thienopyrazoles 2-13, the carboxylic acid hydrazide derivative 1 served as a crucial intermediary. These novel heterocyclic structures were confirmed by analytical and spectroscopic methods (m.p., IR, 1H-NMR, 13C-NMR, and MS). The new compounds 2-13 were evaluated for their antimicrobial activity to identify new drug candidates to combat diseases caused by microbial strains. Against numerous bacterial and fungal strains, certain derivatives of the produced compounds 9 and 11 demonstrated impressive antimicrobial activity. Besides, molecular docking of the newly compounds was conducted against methicillin-resistant Staphylococcus aureus (MRSA) (2 × 3f.pdb). Among the series, compounds 9 and 11 exhibited the best binding affinity towards the target enzyme -10.1 and -10.5 kcal/mol, respectively. The optimized structures and molecular orbitals of the best docked compounds were predicted using DFT (Density Functional Theory) analysis. Our findings represented that both derivatives 9 and 11 could be utilized for development antimicrobial drug candidates.

Pyrazole-based N-phenyl pyrazolines: Synthesis, docking, and pharmacological evaluation

A series of methoxy substituted pyrazole based pyrazoline derivatives (4a-j) were synthesized in good to excellent yield from corresponding pyrazole-chalcones (3a-j). All synthesized derivatives were characterized and screened for their in vitro anti-inflammatory, antioxidant, antidiabetic, and antibacterial activities. Among the series, compounds 4f, 4j, 4a, and 4i showed better anti-inflammatory activity as compared to diclofenac sodium. In DPPH free radical scavenging assay, all the compounds were shown excellent activity and moderate to good activity in SO and NO free radical scavenging assay as compared to standard ascorbic acid. Antibacterial screening of synthesized pyrazolines showed that compounds 4f and 4j have significant antibacterial activity. The compounds 4j, 4f, 4h, 4a, and 4c have shown comparable inhibition of alpha-amylase enzyme leading to good antidiabetic activity as compared to standard acarbose. Molecular docking studies suggest that these compounds have strong binding with COX-2 and alpha-amylase enzyme due to significant capability of aromatic and hydrophobic interaction. The outstanding results of reported compounds in all biological screening will pave the way for the design of new drug candidate bearing pyrazole moiety.

Enantioselective formal (3 + 3) cycloaddition of bicyclobutanes with nitrones enabled by asymmetric Lewis acid catalysis

The absence of catalytic asymmetric methods for synthesizing chiral (hetero)bicyclo[n.1.1]alkanes has hindered their application in new drug discovery. Here we demonstrate the achievability of an asymmetric polar cycloaddition of bicyclo[1.1.0]butane using a chiral Lewis acid catalyst and a bidentate chelating bicyclo[1.1.0]butane substrate, as exemplified by the current enantioselective formal (3 + 3) cycloaddition of bicyclo[1.1.0]butanes with nitrones. In addition to the diverse bicyclo[1.1.0]butanes incorporating an acyl imidazole group or an acyl pyrazole moiety, a wide array of nitrones are compatible with this Lewis acid catalysis, successfully assembling two congested quaternary carbon centers and a chiral aza-trisubstituted carbon center in the pharmaceutically important hetero-bicyclo[3.1.1]heptane product with up to 99% yield and >99% ee.

PIFA-Mediated Intramolecular Dearomatization of Phenol-Tethered 1,2-Diazoles: Synthesis of Spirocyclohexadienone-pyrazolo[3,4-b]piperidinones

AbstractIn recent years, the significance of spirocyclic motifs in drug discovery has increased, owing to their unique ability to engage biological targets. We present the first example of PIFA-mediated dearomative spirocyclization of phenol-tethered pyrazoles, highlighting intramolecular trapping by the pyrazole moiety. This method efficiently affords a variety of spirocyclohexadienone-pyrazolo[3,4-b]piperidinones with yields of up to 82%. Mechanistic studies reveal that the dearomatization process involves a cationic intermediate.

Synthesis and In-Vitro and In-Silico Investigation of Pyrazole Derivatives as Antibacterial and Antifungal Agents

Background: Heterocyclic compounds with O, N, and/or S atoms are highly valuable in drug discovery and development. Their pyrazole moieties find applications in various fields, such as herbicides, corrosion inhibitors, electron transport materials, polymers, and luminescent materials. Consequently, there is a pressing need in medicinal chemistry to develop new antibacterial agents to enhance therapeutic efficacy and safety. Methods: A newer biologically active 1-(4-substitutedphenyl)-5-chloro-3-methyl-1Hpyrazole-4-carboxylic acid analogue was synthesized by the para-substituted phenylhydrazine. All the synthesized compounds were characterized by NMR, mass spectral, and IR spectrum examinations, as well as C, H, and N analyses. The synthesized compounds were screened for antibacterial and antifungal activities. Furthermore, a molecular docking study was performed to elucidate the binding modes of synthesized ligands in the active pockets of DNA gyrase and CYP51 (PDB IDs: 4uro and 5tz1, respectively) for exhibiting the binding modes and predicting the mechanism of action of synthesized ligands. Results: Five compounds (2Rb, 2Re, 2Rg, 2Rh, and 2Ri) demonstrated significant antibacterial action against gram-positive B. subtilis and gram-negative E. coli and antifungal activity against C. albicans and A. niger compared to the standard drugs cefixime and ketoconazole. Furthermore, molecular docking was employed to reveal how the newly synthesized ligands bind within the active pockets. It was found that compound 2Rb demonstrated significant antibacterial activity, and compound 2Rg had good antifungal activity. Conclusion: The current study highlights the unique structural characteristics and significant biological activity of the synthesized compounds. In the pursuit of novel antibacterial and antifungal molecules, these compounds could prove beneficial to society.

Regioselective ligand substitution in square-planar Pt(II) complexes bearing N^C and C^C chelating ligands with pyrazole derivatives

The regioselectivity of the ligand substitution reaction of square-planar Pt(II) complexes with chelating ligands pyridyl-NHC (Py-NHC), phenyl-NHC (Ph-NHC), and phenyl-pyridine (ppy, Ph-Py) was studied. The reaction of the dichlorido Pt(II) complex bearing these chelating ligands in the presence of pyrazole (pz) ligands afforded mono-pyrazole adducts [PtCl(ChL)(pz)]n+ (n = 0 and 1; ChL=chelating ligand (Py-NHC, Ph-NHC, Ph-py)). The structures of the PtCl(pz) complexes with the Py-NHC, Ph-NHC, and Ph-Py chelating ligands were confirmed by X-ray crystallographic analysis. The regioselectivity of the ligand substitution reaction between the pyrazole moieties and chloride ions can be controlled by the strength of the trans effect of the chelating ligands. Based on the structures of the products, a clear trend of Py < NHC < Ph was observed in the trans effect of the chelating ligands. This finding provides a rational synthetic procedure for asymmetric Pt(II) complexes with chelating ligands in a stepwise manner.

Synthesis of novel pyrazole acetals of andrographolide and isoandrographolide as potent anticancer agents.

Globally, cancer is the most prevalent chronic disease-related cause of death. Although there are many anticancer drugs, some of them have adverse effects. Due to their limited side effects, natural products are preferred over synthetic drugs. Andrographolide and its derivatives are known to be potent anticancer agents. In this context, sixteen novel 3,19-(NH-3-aryl-pyrazole) acetals of andrographolide and isoandrographolide (1a-1h, 2a-2g, 2i) from 3-aryl-1-H-pyrazole-4-carboxaldehydes (a-i) were synthesized. All the synthesized compounds were characterized using 1H NMR, 13C NMR, HRMS, FT-IR, and UV-vis spectroscopy. All the compounds were evaluated against a panel of 60 different human cancer cell lines for their anticancer potential at NCI, USA. Four compounds, having promising GI50s (50% growth inhibitory activity) on all 60-cell lines were selected for further in vitro studies. Out of these four compounds, compound 1g exhibited the best IC50 (3.08 μM) against the colon cancer cell line, HCT-116. Cell cycle analysis, annexin V-FITC/PI, and ROS assays revealed that the apoptosis of HCT-116 cells induced by compound 1g could be mainly attributed to the elevated levels of intracellular ROS. Further, the structure-activity relationship revealed that the pyrazole moiety of andrographolide plays a key role in their anticancer properties. These compounds were further examined for in silico ADMET and Lipinski characteristics to assess their potential as lead compounds.

Investigation of Anti-inflammatory and Antioxidant Activities of Promising 1,4,5-Trisubstituted Pyrazoles Derivatives of Chalcone Ditosylates

Patients suffering from chronic pain and inflammatory disorders need novel COX-2 inhibitors to be developed with minimum toxicity to the kidneys, heart, and gastrointestinal tract and with excellent anti-inflammatory activity. The current study centers on an array of 1,4,5-trisubstituted pyrazoles produced via the reaction of ditosylates of chalcones with hydrochloride salt of phenylhydrazine. Chalcone was reacted with HTIB to produce a variety of derivatives of α, β chalcone ditosylates. Phenylhydrazine hydrochloride treatment of these chalcone ditosylates produced distinct 1,4,5-trisubstituted pyrazoles. The conversion process is mediated by 1,2-aryl migrations. IR, 1NMR, and elemental analysis were used to characterize the compounds after they had been purified by recrystallization. Using ascorbic acid as a reference, the DPPH (1,1-diphenyl-2-picrylhydrazyl) technique was used to assess the compounds' in vitro antioxidant activity. The paw edema technique caused by Carrageenan was utilized to assess the compounds' in vivo anti-inflammatory properties. The standard medication used was diclofenac sodium. A plethysmograph was used to measure the volume of the rats' paws. When compared to the standard, the compounds V5D5PH5 and V7D7PH7 showed modest antioxidant activity. When the synthetic pyrazoles were examined for their in vivo anti-inflammatory properties, substances V4D4PH4 and V7D7PH7 outperformed the reference. Here, we attempted to create new, safe, and effective drugs for the treatment of inflammatory disorders and pain by utilizing synthetic pyrazole moiety derivatives. Simple experimentation is used in the proposed study to improve pharmacological activity and yields. In the near future, chalcone ditosylate derivatives will be a powerful tool for selective modification.

Crystal engineering with novel antipyrine derivatives: Insights from X-ray diffraction, Hirshfeld surface analysis, and DFT calculations on intermolecular interactions

In this study, we report the synthesis, structural characterization by X-ray diffraction, vibrational (Infrared and Raman) investigation, Hirshfeld surface analysis, and DFT calculations of three new antipyrine derivatives (1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl) bearing amide groups (1–3). The compounds were synthesized in good yields and characterized spectroscopically. X-ray diffraction revealed that compound 1 crystallizes as a monohydrate in the monoclinic space group P21/c, while compound 3 also crystallizes as a monohydrate in the orthorhombic space group Pccn, exhibiting quasi-isomorphism with 1. Compound 2 crystallizes in the P21/c space group, forming H-bonded centrosymmetric dimers. The crystal packing is stabilized by NH···O and CH···O hydrogen bonds, along with CH···π interactions. FTIR and Raman spectroscopic analysis, supported by DFT calculations, identified key vibrational modes in the amide and pyrazole moieties. Hirshfeld surface analysis indicated that the molecular sheets are primarily formed by hydrogen bonds, with stabilization dominated by electrostatic energy contributions. DFT calculations (PBE0-D3/def2-TZVP) and QTAIM/NCIplot analyses revealed that the H-bonding interactions are energetically significant.

A Brief Review on the Synthesis of 4H‐Chromene‐Embedded Heterocycles

AbstractChromenes are an essential class of oxygen‐containing heterocyclic compounds with intriguing biological activity. It is an important moiety for the discovery of new drug candidates. Chromenes are naturally abundant as alkaloids, tocopherols, flavones, and anthocyanins. The incorporation of 4H‐chromene, along with various bioactive heterocycles such as indole, pyrazole, kojic acid, pyran‐2‐one, quinoline, pyridine, pyrimidine, coumarin, sesamol, furan, uracil, benzoimidazole, benzotriazole, thiazole, isoxazole and barbituric acid moieties, into a molecular scaffold has the potential to combine the properties of both components. The synergistic effect of combining different heterocyclic moieties within a 4H‐chromene nucleus results in the formation of valuable compounds with significant biological importance. This review summarizes the different synthetic techniques used for preparing 4H‐chromene‐embedded heterocycles. The common mechanisms of key reactions and the significance of the method are discussed.

Synthesis of new polyazomethine-based pyrazole moieties as promising biologically active macromolecules

ABSTRACT Using the polycondensation technique, it was possible to synthesize a new class of biologically active polyazomethine based on pyrazole moiety. The polymerization occurred through the interaction between terephthalaldehyde and various derivatives of diaminopyrazole. The polymers that were made were given the letters PAZm/Py1–4 to reflect the different diaminopyrazole derivatives that were used. The monomer and polymer structures were investigated by common spectral characterization methods. The new PAZm/Py1–4 were examined by gel permeation chromatography (GPC), solubility tests, thermogravimetric analysis (TGA), X-ray diffraction analysis (XRD), and scanning electron microscopy (SEM). The newly synthesized polymers have high thermal stability and normal crystalline behavior. The antibacterial properties of all synthesized polymers were evaluated against the Gram-positive bacteria and the Gram-negative bacteria. Additionally, two types of fungi were used to test how well the prepared polymers worked against fungi. PAZm/Py1 and PAZm/Py4 showed slight antibacterial activity against the representative Gram-positive bacteria, while PAZm/Py2 and PAZm/Py3 had no significant influence. All the tested polymers showed slight to moderate antibacterial activity against the representative Gram-negative bacteria. PAZm/Py1 and PAZm/Py4 had a greater antifungal influence than other polymers.

Understanding adsorption ability of CNT (6, 6-6) and BNNT (6, 6-7) nanotubes for a novel hybrid pyrazole-indole drug, InPy-7a

The quest for enhanced drug delivery efficacy across diverse physiological conditions has spurred the exploration of various nanomaterials, including carbon-based materials like carbon nanotubes (CNTs) and boron nitride nanotubes (BNNTs). These materials offer high surface areas conducive to increased drug loading, with considerations such as surface charge, size, shape, and biocompatibility being paramount. The hybrid drug, synthesized by combining indole derivatives with a pyrazole moiety, has shown promising cytotoxicity against various cancer cell lines. In this context, we have explored the adsorption ability of CNT (6, 6-6) and BNNT (6, 6-7) nanotubes for a novel hybrid drug, InPy-7a, using density functional theory (DFT) calculations. Our study has aimed to elucidate the adsorption mechanisms and electronic properties of InPy-7a on the surfaces of CNT (6, 6-6) and BNNT (6, 6-7). Through computational tools, we have analyzed the geometry optimization of InPy-7a onto the nanotube surfaces, evaluating molecular interactions, quantum descriptors, frontier molecular orbitals (FMO), natural bond orbitals (NBO), nuclear magnetic resonance (NMR), and molecular electrostatic potential (MEP). Our results have illuminated the underlying mechanisms by revealing unique interactions and electronic changes during complexation. Based on predicted electronic aspects and molecular interactions, the CNT@InPy-7a-S5 complex system showed greater chemical reactivity, adsorption, and stability than BNNT@InPy-7a-S6. These findings open up opportunities for additional experimental validations and offer insightful information about the possible uses of drug delivery systems based on nanotubes.

Synthesis of Novel Acetamide, Acrylamide, Pyrazole, and Pyridine Derivatives Comprising Benzothiazole Moiety as Antioxidant Agents

Synthesis of Novel Acetamide, Acrylamide, Pyrazole, and Pyridine Derivatives Comprising Benzothiazole Moiety as Antioxidant Agents

Synthesis, characterization, and anticancer effect of novel Pyrazolopyranopyrimidines

Two novel β-enaminonitrile derivatives 5a,b bearing pyrano[2,3-c]pyrazole moiety were synthesized using Multi Component Reaction (MCR) technique by reacting the ethyl benzoylacetate, phenylhydrazine, malononitrie, and various aldehydes in different conditions. A series of fused pyrazolopyrane derivatives (6–13) was constructed from a compound, 6-amino-4-(2-bromophenyl)-1,3-diphenyl-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (5a), as a building block. The novel constructed compounds were analyzed by spectra data as FT-IR, 1H NMR, 13C NMR, mass spectra and elemental analysis. The cytotoxic activity of the prepared compounds was evaluated against three different cancer cell lines and the IC50 was determined for each compound, including MDA-MB-231 (a breast cancer cell line), A549 (a lung cancer cell line) and WI-38 (a lung fibroblast cell line). Ethyl-N-(4-(2-bromophenyl)-5-cyano-1,3-diphenyl-1,4-dihydropyrano[2,3-c]pyrazol-6-yl)formimidate (11) and 4-(2‑bromo phenyl)-1,3-diphenyl-1,4-dihydropyrazolo[4′,3′:5,6]pyrano[2,3-d]pyrimidin-5-amine (13) were among the most potent cytotoxic activity against the cancer cells with IC50 values of 18.03 ± 0.98 - 46.23 ± 3.45 µM. Compound (11) showed more potent topoisomerase inhibitory activity than the positive control etoposide as per the IC50 values, 35.05 µM ± 2.1 and 46.54 µM ± 2.8, respectively. The results of the molecular docking studies supported the in vitro assay results for the active compounds.

Chiral versus achiral crystal structures of 4-benzyl-1H-pyrazole and its 3,5-di-amino derivative.

The crystal structures of 4-benzyl-1H-pyrazole (C10H10N2, 1) and 3,5-di-amino-4-benzyl-1H-pyrazole (C10H12N4, 2) were measured at 150 K. Although its different conformers and atropenanti-omers easily inter-convert in solution by annular tautomerism and/or rotation of the benzyl substituent around the C(pyrazole)-C(CH2) single bond (as revealed by 1H NMR spectroscopy), 1 crystallizes in the non-centrosymmetric space group P21. Within its crystal structure, the pyrazole and phenyl aromatic moieties are organized into alternating bilayers. Both pyrazole and phenyl layers consist of aromatic rings stacked into columns in two orthogonal directions. Within the pyrazole layer, the pyrazole rings form parallel catemers by N-H⋯N hydrogen bonding. Compound 2 adopts a similar bilayer structure, albeit in the centrosymmetric space group P21/c, with pyrazole N-H protons as donors in N-H⋯π hydrogen bonds with neighboring pyrazole rings, and NH2 protons as donors in N-H⋯N hydrogen bonds with adjacent pyrazoles and other NH2 moieties. The crystal structures and supra-molecular features of 1 and 2 are contrasted with the two known structures of their analogs, 3,5-dimethyl-4-benzyl-1H-pyrazole and 3,5-diphenyl-4-benzyl-1H-pyrazole.