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European Journal of Medicinal Chemistry Dec 2022The fusion of pyrazole scaffold with other skeletons creates a class of attractive molecules, demonstrating significant biological and chemical potentiality in the... (Review)
Review
The fusion of pyrazole scaffold with other skeletons creates a class of attractive molecules, demonstrating significant biological and chemical potentiality in the development of medicinal chemistry. Over the past few decades, numerous biologically active molecules featuring fused pyrazole moieties have been excavated and synthesized, some of which represented by sildenafil have been marketed as drugs, and the biological importance together with chemical synthesis strategies of fused pyrazole compounds, including structural modification based on lead compounds, have been steadily progressing. In this review, we focused our attention on the biological importance of fused pyrazoles and highlighted recent progress in the synthesis of this framework over the past 10 years. What' s more, the limitations, challenges, and future prospects were proposed, wishing to provide references for the development of pyrazole fused frameworks in the field of medicinal chemistry. Contents.
Topics: Pyrazoles; Chemistry, Pharmaceutical
PubMed: 36126386
DOI: 10.1016/j.ejmech.2022.114739 -
Molecules (Basel, Switzerland) Jul 2020Nitrated-pyrazole-based energetic compounds have attracted wide publicity in the field of energetic materials (EMs) due to their high heat of formation, high density,... (Review)
Review
Nitrated-pyrazole-based energetic compounds have attracted wide publicity in the field of energetic materials (EMs) due to their high heat of formation, high density, tailored thermal stability, and detonation performance. Many nitrated-pyrazole-based energetic compounds have been developed to meet the increasing demands of high power, low sensitivity, and eco-friendly environment, and they have good applications in explosives, propellants, and pyrotechnics. Continuous and growing efforts have been committed to promote the rapid development of nitrated-pyrazole-based EMs in the last decade, especially through large amounts of Chinese research. Some of the ultimate aims of nitrated-pyrazole-based materials are to develop potential candidates of castable explosives, explore novel insensitive high energy materials, search for low cost synthesis strategies, high efficiency, and green environmental protection, and further widen the applications of EMs. This review article aims to present the recent processes in the synthesis and physical and explosive performances of the nitrated-pyrazole-based Ems, including monopyrazoles with nitro, bispyrazoles with nitro, nitropyrazolo[4,3-]pyrazoles, and their derivatives, and to comb the development trend of these compounds. This review intends to prompt fresh concepts for designing prominent high-performance nitropyrazole-based EMs.
Topics: Explosive Agents; Nitrates; Nitro Compounds; Pyrazoles; Thermodynamics
PubMed: 32751631
DOI: 10.3390/molecules25153475 -
Organic & Biomolecular Chemistry Mar 2022Pyrazolones and pyrazoles, featuring nitrogen-nitrogen bonds, are two of the most important classes of heterocycles, owing to their widespread occurrence in medicinal... (Review)
Review
Pyrazolones and pyrazoles, featuring nitrogen-nitrogen bonds, are two of the most important classes of heterocycles, owing to their widespread occurrence in medicinal chemistry and functional materials. The last decade has witnessed a rapid increase in the construction of chiral pyrazolone and pyrazole derivatives, with the application of pyrazolone derivatives as powerful synthons. Since our last review in 2018, a large number of new achievements has emerged in this area, requiring a timely update. Thus, this review summarizes these elegant achievements based on the multiple reactive sites of different pyrazolone synthons. In addition, important mechanisms and interesting biological investigations relating to the corresponding products are also discussed.
Topics: Catalytic Domain; Nitrogen; Pyrazoles; Pyrazolones; Stereoisomerism
PubMed: 35234777
DOI: 10.1039/d1ob02426d -
Organic & Biomolecular Chemistry Nov 2022Pyrazole is an essential structural component of many pharmaceuticals and agrochemicals. The synthesis of pyrazoles has been a subject of intense research for several... (Review)
Review
Pyrazole is an essential structural component of many pharmaceuticals and agrochemicals. The synthesis of pyrazoles has been a subject of intense research for several decades. Many transformations are now available to conveniently access pyrazoles from readily available starting materials. Conventionally, the synthesis of pyrazoles involves the condensation reaction of hydrazines with 1,3-dicarbonyl compounds or their synthetic equivalents and 1,3-dipolar cycloaddition reactions of diazo compounds with dipolarophiles. The present review provides comprehensive information on the development of synthetic approaches to access pyrazoles [3 + 2] cycloaddition reactions of diazo compounds and their synthetic equivalents.
Topics: Cycloaddition Reaction; Azo Compounds; Pyrazoles; Hydrazines
PubMed: 36331498
DOI: 10.1039/d2ob01918c -
Fundamental & Clinical Pharmacology Apr 2021The therapeutic limitations and poor management of inflammatory conditions are anticipated to impact patients negatively over the coming decades. Following the synthesis... (Review)
Review
The therapeutic limitations and poor management of inflammatory conditions are anticipated to impact patients negatively over the coming decades. Following the synthesis of the first pyrazole-antipyrine in 1887, several other derivatives have been screened for anti-inflammatory, analgesic, and antipyretic activities. Arguably, the pyrazole ring, as a major pharmacophore and central scaffold partly, defines the pharmacological profile of several derivatives. In this review, we explore the structural-activity relationship that accounts for the pharmacological profile of pyrazole derivatives and highlights future research perspectives capable of optimizing current advancement in the search for safe and efficacy anti-inflammatory drugs. The flourishing research into the pyrazole derivatives as drug candidates has advanced our understanding of inflammation-related diseases and treatment.
Topics: Anti-Inflammatory Agents; Drug Design; Humans; Inflammation; Molecular Structure; Pyrazoles
PubMed: 33171533
DOI: 10.1111/fcp.12629 -
ChemMedChem Sep 2023In previous studies, we synthesized different imidazo-pyrazoles 1 and 2 with interesting anticancer, anti-angiogenic and anti-inflammatory activities. To further extend...
In previous studies, we synthesized different imidazo-pyrazoles 1 and 2 with interesting anticancer, anti-angiogenic and anti-inflammatory activities. To further extend the structure-activity relationships of imidazo-pyrazole scaffold and to identify novel antiproliferative/anti-inflammatory agents potentially active with multi-target mechanisms, a library of compounds 3-5 has been designed and synthesized. The chemical modifications characterizing the novel derivatives include: i) decoration of the catechol ring with groups with different electronic, steric and lipophilic properties (compounds 3); ii) insertion of a methyl group on C-6 of imidazo-pyrazole scaffold (compounds 4); iii) shift of the acylhydrazonic substituent from position 7 to 6 of the imidazo-pyrazole substructure (compounds 5). All synthesized compounds were tested against a panel of cancer and normal cell lines. Derivatives 3 a, 3 e, 4 c, 5 g and 5 h showed IC values in the low micromolar range against selected tumor cell lines and proved to have antioxidant properties, being able to inhibit ROS production in human platelet. In silico calculation predicted favourable drug-like and pharmacokinetic properties for the most promising compounds. Furthermore, molecular docking and molecular dynamic simulations suggested the ability of most active derivative 3 e to interact with colchicine binding site in the polymeric tubulin α/tubulin β/stathmin4 complex.
Topics: Humans; Molecular Docking Simulation; Tubulin; Structure-Activity Relationship; Cell Line, Tumor; Pyrazoles; Antineoplastic Agents; Drug Screening Assays, Antitumor; Molecular Structure; Cell Proliferation
PubMed: 37366115
DOI: 10.1002/cmdc.202300252 -
European Journal of Medicinal Chemistry Sep 2023Chemotherapeutics occupy a pivotal role in the medication of different types of cancers, but the prevalence and mortality rates of cancer remain high. The drug... (Review)
Review
Chemotherapeutics occupy a pivotal role in the medication of different types of cancers, but the prevalence and mortality rates of cancer remain high. The drug resistance and low specificity of current available chemotherapeutics are the main barriers for the effective cancer chemotherapy, evoking an immediate need for the development of novel anticancer agents. Pyrazole is a highly versatile five-membered heterocycle with two adjacent nitrogen atoms and possesses remarkable therapeutic effects and robust pharmacological potency. The pyrazole derivatives especially pyrazole hybrids have demonstrated potent in vitro and in vivo efficacies against cancers through multiple mechanisms, inclusive of apoptosis induction, autophagy regulation, and cell cycle disruption. Moreover, several pyrazole hybrids such as crizotanib (pyrazole-pyridine hybrid), erdafitinib (pyrazole-quinoxaline hybrid) and ruxolitinib (pyrazole-pyrrolo [2,3-d]pyrimidine hybrid) have already been approved for the cancer therapy, revealing that pyrazole hybrids are useful scaffolds to develop novel anticancer agents. The purpose of this review is to summarize the current scenario of pyrazole hybrids with potential in vivo anticancer efficacy along with mechanisms of action, toxicity, and pharmacokinetics, covering papers published in recent 5 years (2018-present), to facilitate further rational exploitation of more effective candidates.
Topics: Humans; Structure-Activity Relationship; Neoplasms; Antineoplastic Agents; Pyrazoles; Azoles
PubMed: 37209450
DOI: 10.1016/j.ejmech.2023.115495 -
Current Organic Synthesis 2021Privileged scaffolds are of high importance for molecules containing the pyrazole subunit due to their broad spectrum of pharmacological activities. For this reason, a...
BACKGROUND
Privileged scaffolds are of high importance for molecules containing the pyrazole subunit due to their broad spectrum of pharmacological activities. For this reason, a method that is more efficient needs to be developed for the preparation of pyrazole derivatives.
OBJECTIVE
The purpose of this study was the optimisation of the conventional synthesis of the pyrazole ring and the oxidation of phenyl-1H-pyrazole-4-carbaldehyde to phenyl-1H-pyrazole-4-carboxylic acid through Microwave- Assisted Organic Synthesis (MAOS).
METHODS
We performed a comparison between conventional synthesis and conventional synthesis with microwave heating using the synthesis method of pyrazole ring described by Finar and Godfrey and for the oxidation of phenyl-1H-pyrazole-4-carbaldehyde, the method described by Shriner and Kleiderer was used.
RESULTS
MAOS reduces the reaction time to obtain all compounds compared to conventional heating. At a temperature of 60°C, 5 minutes of reaction time, and power of 50 W, the yield of phenyl-1H-pyrazoles (3a-m) compounds was in the range of 91 - 98% using MAOS, which is better than conventional heating (72 - 90%, 75ºC, 2 hours). An improvement in the yield for the oxidation reaction was also achieved with MAOS. The compounds (5a-m) were obtained with yields ranging from 62 - 92% (80ºC, 2 minutes, 150 W), while the yields with conventional heating were in the range of 48 - 85% (80ºC, 1 hour). The 26 compounds were achieved through an easy work-up procedure with no chromatographic separation. The pure products were characterised by the spectral data obtained from IR, MS, H and C NMR or HSQC/HMBC techniques.
CONCLUSION
The advantages of MAOS include short reaction time and increased yield, due to which it is an attractive option for pyrazole compounds synthesis.
Topics: Carboxylic Acids; Chemistry Techniques, Synthetic; Microwaves; Pyrazoles
PubMed: 34886771
DOI: 10.2174/1570179418666210618162518 -
Molecules (Basel, Switzerland) Jul 2020The pyrazole nucleus has long been known as a privileged scaffold in the synthesis of biologically active compounds. Within the numerous pyrazole derivatives developed... (Review)
Review
The pyrazole nucleus has long been known as a privileged scaffold in the synthesis of biologically active compounds. Within the numerous pyrazole derivatives developed as potential drugs, this review is focused on molecules characterized by a urea function directly linked to the pyrazole nucleus in a different position. In the last 20 years, the interest of numerous researchers has been especially attracted by pyrazolyl-ureas showing a wide spectrum of biological activities, ranging from the antipathogenic activities (bacteria, plasmodium, toxoplasma, and others) to the anticarcinogenic activities. In particular, in the anticancer field, pyrazolyl-ureas have been shown to interact at the intracellular level on many pathways, in particular on different kinases such as Src, p38-MAPK, TrKa, and others. In addition, some of them evidenced an antiangiogenic potential that deserves to be explored. This review therefore summarizes all these biological data (from 2000 to date), including patented compounds.
Topics: Chemistry Techniques, Synthetic; Chemistry, Pharmaceutical; Humans; Pharmaceutical Preparations; Pyrazoles; Structure-Activity Relationship; Urea
PubMed: 32751358
DOI: 10.3390/molecules25153457 -
International Journal of Molecular... May 20204-Pyrazoles are emerging scaffolds for "click" chemistry. Late-stage fluorination with Selectfluor is found to provide a reliable route to 4-fluoro-4-methyl-4-pyrazoles....
4-Pyrazoles are emerging scaffolds for "click" chemistry. Late-stage fluorination with Selectfluor is found to provide a reliable route to 4-fluoro-4-methyl-4-pyrazoles. 4-Fluoro-4-methyl-3,5-diphenyl-4-pyrazole (MFP) manifested 7-fold lower Diels-Alder reactivity than did 4,4-difluoro-3,5-diphenyl-4-pyrazole (DFP), but higher stability in the presence of biological nucleophiles. Calculations indicate that a large decrease in the hyperconjugative antiaromaticity in MFP relative to DFP does not lead to a large loss in Diels-Alder reactivity because the ground-state structure of MFP avoids hyperconjugative antiaromaticity by distorting into an envelope-like conformation like that in the Diels-Alder transition state. This predistortion enhances the reactivity of MFP and offsets the decrease in reactivity from the diminished hyperconjugative antiaromaticity.
Topics: Chemistry Techniques, Synthetic; Cycloaddition Reaction; Fluorine; Glutathione; Kinetics; Models, Molecular; Molecular Conformation; Molecular Structure; Organic Chemicals; Pyrazoles; Stereoisomerism; Thermodynamics; Ultraviolet Rays
PubMed: 32486503
DOI: 10.3390/ijms21113964