-
Future Medicinal Chemistry Nov 2023Pyrazole or 1-pyrazole, a five-membered 1,2-diazole, is found in several approved drugs and some bioactive natural products. A myriad number of derivatives of this small... (Review)
Review
Pyrazole or 1-pyrazole, a five-membered 1,2-diazole, is found in several approved drugs and some bioactive natural products. A myriad number of derivatives of this small molecule have been reported in clinical and preclinical studies for the potential treatment of several diseases. The number of drugs containing a pyrazole nucleus has increased significantly in the last 10 years. Some of the best-selling drugs in this class are ibrutinib, ruxolitinib, axitinib, niraparib and baricitinib, and are used to treat different types of cancers; lenacapavir to treat HIV; riociguat to treat pulmonary hypertension; and sildenafil to treat erectile dysfunction. Several aniline-derived pyrazole compounds have been reported as potent antibacterial agents with selective activity against methicillin-resistant and vancomycin-resistant enterococci. Here, we discuss the pyrazole-derived drugs reported up to September 2023.
Topics: Male; Humans; Methicillin-Resistant Staphylococcus aureus; Anti-Bacterial Agents; Pyrazoles; Drug Discovery; Microbial Sensitivity Tests
PubMed: 37933613
DOI: 10.4155/fmc-2023-0207 -
Journal of Agricultural and Food... Sep 2022A heterocyclic replacement strategy has been applied attempting to further optimize the biological properties of the new insecticide tyclopyrazoflor, a...
A heterocyclic replacement strategy has been applied attempting to further optimize the biological properties of the new insecticide tyclopyrazoflor, a pyridinyl-pyrazole compound with excellent activity against sap-feeding insects recently discovered by Corteva. Our research program on this novel chemical class of insecticide was targeted to evaluate the importance of both the pyridyl and pyrazole moieties on the biological activity, properties, and structure-activity. Synthetic methodologies have been developed delivering our designed target compounds in moderate to good yields. In our attempt to rationalize the biological activity differences of tyclopyrazoflor analogues, a potential surface analysis based on a density functional theory (DFT) calculation and DFT-derived Multiwfn and VMD program model was performed. Furthermore, the SwissBioisostere online database was applied as a great source for inspiration for bioisosteric replacements.
Topics: Insecticides; Pyrazoles; Structure-Activity Relationship
PubMed: 35561416
DOI: 10.1021/acs.jafc.2c00654 -
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 -
Archiv Der Pharmazie Oct 2021A series of novel pyrazolo[3,4-d]pyrimidin-4-one derivatives were synthesized and evaluated for their anti-phosphodiesterase-5 (PDE-5) activity. A total of 28 compounds,... (Comparative Study)
Comparative Study
A series of novel pyrazolo[3,4-d]pyrimidin-4-one derivatives were synthesized and evaluated for their anti-phosphodiesterase-5 (PDE-5) activity. A total of 28 compounds, containing alkyl and aryl groups at the 1-N and 3-C positions on the pyrazole ring, and also bearing different alkyl substituents on the piperazine ring were synthesized. Four compounds (4d, 5d, 6d, and 5o) were found to have better inhibitory activity against PDE-5 (IC < 10 nM). All four of the most active compounds contain a phenyl ring at the N1 position. Compounds containing a 3,5-dimethylpiperazinyl group show better activity than others. These results suggest that compound 5o can be used as a lead structure for developing new inhibitors of PDE-5.
Topics: Inhibitory Concentration 50; Phosphodiesterase 5 Inhibitors; Pyrazoles; Pyrimidines; Sildenafil Citrate; Structure-Activity Relationship
PubMed: 34131943
DOI: 10.1002/ardp.202100145 -
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 -
Current Organic Synthesis Oct 2021Heterocycles are the main structural motif of DNA and RNA and play a crucial role in various chemical reactions of metabolisms. Therefore, heterocyclic compounds show... (Review)
Review
Heterocycles are the main structural motif of DNA and RNA and play a crucial role in various chemical reactions of metabolisms. Therefore, heterocyclic compounds show good physiological and pharmacological properties. Coumarin and pyrazole scaffolds are present in many commercial drug molecules and natural products. This review overviews the progress made in the synthesis and functionalization of the coumarin- pyrazole hybrid heterocycle. It also includes discussion on the possible reactive sites of heterocycles, functionalization, and mechanistic pathways to incorporate pyrazole pharmacophore unit in synthesis. Several synthesis and biological studies reveal that the combination of the coumarin-pyrazole moiety is a prominent structural motif to find lead compounds in drug discovery.
Topics: Coumarins; Drug Discovery; Pyrazoles
PubMed: 33645484
DOI: 10.2174/1570179418666210301122322