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Chemical Communications (Cambridge,... Apr 2022Indazole and pyrazole are renowned as a prodigious class of heterocycles having versatile uses in medicinal as well as industrial chemistry. Considering sustainable... (Review)
Review
Indazole and pyrazole are renowned as a prodigious class of heterocycles having versatile uses in medicinal as well as industrial chemistry. Considering sustainable approaches, recently, photocatalysis has become an indispensable tool in organic chemistry due to its application for the activation of small molecules and the use of a clean energy source. In this review, we have highlighted the use of metal-based photocatalysts, organic photoredox catalysts, energy transfer photocatalysts and electron-donor-acceptor complexes in the functionalization of indazole and pyrazole. This perspective is arranged based on the types of functionalization reactions on indazole and pyrazole. A detailed discussion regarding the reaction mechanism of each reaction is given to provide a comprehensive guide to the reader. Finally, a summary of existing challenges and the future outlook towards the development of efficient photocatalytic methods for functionalization of these heterocycles is also presented.
Topics: Catalysis; Indazoles; Light; Pyrazoles
PubMed: 35294515
DOI: 10.1039/d2cc00002d -
Bioorganic & Medicinal Chemistry Letters Aug 2022The synthesis of eight novel pyrazole-tetrazole compounds are presented. Their structures are identified by NMR and FTIR spectroscopy, mass spectrometry as well as...
The synthesis of eight novel pyrazole-tetrazole compounds are presented. Their structures are identified by NMR and FTIR spectroscopy, mass spectrometry as well as elemental analysis. Their in-vitro α-amylase inhibition and haemoglobin antiglycation activity were examined by spectrophotometric methods. All compounds possess both activities, especially molecules entitled 2-(1-((5-methyl-1H-pyrazol-3-yl)methyl)-1H-tetrazol-5-yl)pyridine 4 and 2-(1-((1-ethyl-5-methyl-1H-pyrazol-3-yl)methyl)-1H-tetrazol-5-yl)pyridine 8 which were found to be extremely potent compared to the positive controls. The SAR study proved the influence of the alkylation position of pyrazole derivative on the tetrazole ring, the nature of substituent on the tetrazolic carbon atom and the nature of the group at the nitrogen atom of the pyrazole ring on both α-amylase and glycation inhibition activity. Compounds 4 and 8 could be a good drug candidate to treat Type 2 diabetes.
Topics: Diabetes Mellitus, Type 2; Humans; Pyrazoles; Pyridines; Tetrazoles; alpha-Amylases
PubMed: 35569687
DOI: 10.1016/j.bmcl.2022.128785 -
ChemMedChem Sep 2021Pyrazole-thiazole core-containing compound KP-40 and 20 novel derivatives were designed and synthesized through traditional SAR analysis. These molecules displayed...
Pyrazole-thiazole core-containing compound KP-40 and 20 novel derivatives were designed and synthesized through traditional SAR analysis. These molecules displayed adjunctive activity with meropenem against Gram-negative bacteria evidenced by a range of fractional inhibitory concentration (FIC=0.5-0.25) and minimum adjunctive concentration (MAC=128-32 μM) values. Of this series of molecules, four compounds displayed notable adjunctive potential, with FIC and MAC values of 0.25 and 32 μM, respectively. Moreover, the solubility of these compounds was improved to an acceptable range. Further analysis using our "in house" permeation and efflux multi parameter optimization (PEMPO) algorithm revealed key physicochemical properties that may be critical for the development of active Gram-negative antibacterials. Taking PEMPO scores into consideration prior to executing synthesis of analogs may be a simple, yet rapid and effective strategy that can be used in conjunction with traditional SAR approaches to aid in the design of potent Gram-negative antibacterials.
Topics: Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Dose-Response Relationship, Drug; Meropenem; Microbial Sensitivity Tests; Molecular Structure; Pyrazoles; Structure-Activity Relationship; Thiazoles
PubMed: 34096189
DOI: 10.1002/cmdc.202100321 -
European Journal of Medicinal Chemistry Oct 2014Condensed pyrazole derivatives are important heterocyclic compounds due to their excellent biological activities and have been widely applied in pharmaceutical and... (Review)
Review
Condensed pyrazole derivatives are important heterocyclic compounds due to their excellent biological activities and have been widely applied in pharmaceutical and agromedical fields. In recent years, numerous condensed pyrazole derivatives have been synthesized and advanced to clinic studies with various biological activities. In this review, we summarized the reported synthesis methods of condensed pyrazole derivatives from 2010 until now. All compounds are divided into three parts according to the rings connected to pyrazole-ring, i.e. [5, 5], [5,F 6], and [5, 7]-condensed pyrazole derivatives. The biological activities and applications in pharmaceutical fields are briefly introduced to offer an orientation for the design and synthesis of condensed pyrazole derivatives with good biological activities.
Topics: Chemistry Techniques, Synthetic; Drug Design; Humans; Pyrazoles
PubMed: 25104650
DOI: 10.1016/j.ejmech.2014.07.102 -
Medicinal Chemistry (Shariqah (United... 2021From the point of view of medicinal chemistry, compounds containing phenolic and pyrazolic moiety are significant since they are often constituents of bioactive...
BACKGROUND
From the point of view of medicinal chemistry, compounds containing phenolic and pyrazolic moiety are significant since they are often constituents of bioactive compounds.
OBJECTIVE
The aims of this study were to synthesize pyrazole derivatives of medically relevant phenolic acids, confirm their structure, and evaluate their antioxidative and anti-LOX activities.
METHODS
Phenolic pyrazole derivatives were obtained, starting from esters of medically relevant phenolic acids. The structures of all obtained compounds were determined by NMR and IR spectroscopy, and UV-Vis spectrophotometry. In addition, the single-crystal X-ray diffraction was used. Pyrazole derivatives were tested for their in vitro antioxidative (DPPH assay), and lipoxygenase (LOX) inhibitory activities. Radical quenching mechanism was estimated using DFT and thermodynamic approach, while molecular docking was used to estimate the binding mode within the enzyme.
RESULTS
Pyrazole derivatives were obtained in high yields. The crystal structure of a new compound 3e was determined. Pyrazole derivative with catechol moiety 3d exhibited excellent radical scavenging activity, while compound 3b exhibited the best anti-LOX activity. Molecular docking study revealed that there is no direct interaction of any ligand with the active site of LOX-Ib, but pyrazoles 3a-e behave as inhibitors blocking the approach of linoleic acid to the active site.
CONCLUSION
In this research, protocatechuic and vanillic acid pyrazole derivatives have been obtained for the first time. In vitro antioxidative assay suggests that pyrazole derivate of protocatechuic acid is a powerful radical scavenger, while anti-LOX assay indicates a pyrazole derivative with 4-hydroxyphenyl moiety.
Topics: Antioxidants; Catalytic Domain; Cell Line, Tumor; Drug Design; Humans; Hydroxybenzoates; Ligands; Lipoxygenase Inhibitors; Molecular Docking Simulation; Pyrazoles; Structure-Activity Relationship
PubMed: 32484771
DOI: 10.2174/1573406416666200602152643 -
European Journal of Medicinal Chemistry Jun 2015In this review we report the recent advances in bioactive system containing pyrazole fused with a five membered heterocycle, covering the time span of the last decade.... (Review)
Review
In this review we report the recent advances in bioactive system containing pyrazole fused with a five membered heterocycle, covering the time span of the last decade. All of them are represented around the common structure of the pyrazole ring fused with another five membered heterocycle containing the nitrogen, sulfur and oxygen atoms in all their possible combinations. The classification we have used is based in terms of the therapeutic area providing, when possible, some general conclusions on the targets and mechanisms of action as well as the structure-activity relationships of the molecules.
Topics: Animals; Drug Discovery; Humans; Pyrazoles
PubMed: 25549911
DOI: 10.1016/j.ejmech.2014.12.023 -
Journal of Visualized Experiments : JoVE Jun 2019A synthetic process for the preparation of a variety of 1-aryl-1H-pyrazole-5-amines was developed. The microwave-mediated nature of this method makes it efficient in...
A synthetic process for the preparation of a variety of 1-aryl-1H-pyrazole-5-amines was developed. The microwave-mediated nature of this method makes it efficient in both time and resources and utilizes water as the solvent. 3-Aminocrotononitrile or an appropriate α-cyanoketone is combined with an aryl hydrazine and dissolved in 1 M HCl. The mixture is then heated in a microwave reactor at 150 °C, typically for 10-15 min. The product can be readily obtained by basifying the solution with 10% NaOH and isolating the desired compound with a simple vacuum filtration. The use of water as a solvent in this reaction lends to its ease and utility in production, and this method is easily reproducible with a variety of functional groups. Typical isolated yields range from 70-90%, and reactions can be performed on the milligram to gram scale with little to no change in observed yields. Some of the applications of these molecules and their derivatives include pesticides, anti-malarials, and chemotherapeutics, among many others.
Topics: Amines; Microwaves; Pyrazoles
PubMed: 31282901
DOI: 10.3791/59896 -
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 -
Bioorganic Chemistry Feb 2022Both HIV and DENV are serious threats to human life, health and social economy today. So far, no vaccine for either HIV or DENV has been developed successfully. The...
Both HIV and DENV are serious threats to human life, health and social economy today. So far, no vaccine for either HIV or DENV has been developed successfully. The research on anti-HIV or DENV drugs is still of great significance. In this study we developed a series of novel 2-Aryl-1H-pyrazole-S-DABOs with C6-strucutral optimizations as potent NNRTIs, among which, 8 compounds had low cytotoxicity and EC values in the range of 0.0508 ∼ 0.0966 μM, and their selectivity index was SI > 1415 ∼ 3940. In particular, two compounds 4a and 4b were identified to have good inhibitory effects on DENV of four serotypes. The EC of compound 4a and 4b against DENV-II (13.2 μM and 9.23 μM, respectively) were better than that of the positive control ribavirin (EC = 40.78 μM). In addition, the effect of C-6 substituents on the anti-HIV or anti-DENV activity of these compounds was also discussed.
Topics: Antiviral Agents; Dengue Virus; Dose-Response Relationship, Drug; HIV-1; Microbial Sensitivity Tests; Molecular Structure; Pyrazoles; Structure-Activity Relationship
PubMed: 34836643
DOI: 10.1016/j.bioorg.2021.105494 -
Archiv Der Pharmazie Aug 2020Pyrazole, coumarin, and quinoline are medicinally important moieties. In this study, two series of novel pyrazole-coumarin chalcones and pyrazole-quinoline chalcones...
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 H and 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 Schrödinger software, and these compounds exhibited good pharmacological and oral absorption properties.
Topics: Antitubercular Agents; Chalcones; Coumarins; Microbial Sensitivity Tests; Molecular Docking Simulation; Molecular Structure; Mycobacterium tuberculosis; Pyrazoles; Quinolines; Software
PubMed: 32484273
DOI: 10.1002/ardp.202000077