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Molecules (Basel, Switzerland) Feb 2021The remarkable prevalence of pyrazole scaffolds in a versatile array of bioactive molecules ranging from apixaban, an anticoagulant used to treat and prevent blood clots... (Review)
Review
The remarkable prevalence of pyrazole scaffolds in a versatile array of bioactive molecules ranging from apixaban, an anticoagulant used to treat and prevent blood clots and stroke, to bixafen, a pyrazole-carboxamide fungicide used to control diseases of rapeseed and cereal plants, has encouraged both medicinal and organic chemists to explore new methods in developing pyrazole-containing compounds for different applications. Although numerous synthetic strategies have been developed in the last 10 years, there has not been a comprehensive overview of synthesis and the implication of recent advances for treating neurodegenerative disease. This review first presents the advances in pyrazole scaffold synthesis and their functionalization that have been published during the last decade (2011-2020). We then narrow the focus to the application of these strategies in the development of therapeutics for neurodegenerative diseases, particularly for Alzheimer's disease (AD) and Parkinson's disease (PD).
Topics: Alzheimer Disease; Animals; Humans; Molecular Structure; Parkinson Disease; Pyrazoles
PubMed: 33668128
DOI: 10.3390/molecules26051202 -
European Journal of Medicinal Chemistry 2013Pyrazole has been the topic of interest for thousands of researchers across the world because of its wide spectrum pharmacological activities. Various structural... (Review)
Review
Pyrazole has been the topic of interest for thousands of researchers across the world because of its wide spectrum pharmacological activities. Various structural modifications of the pyrazole nucleus have been made to explore its characteristics and biological potential. The present work aims to review the use of molecular modeling in the designing of novel pyrazole analogs that may target various receptors such as protein kinase inhibitor, tyrosine kinase, Aurora-A kinase, tumor growth factor (TGF), cyclin dependent kinase (CDK) and fibroblast growth factor (FGF), which are significant for the management of cancer. An insight has been given in this article for the importance of pyrazoles in the treatment of cancer and the perspectives that they hold for future research.
Topics: Animals; Antineoplastic Agents; Humans; Models, Molecular; Neoplasms; Pyrazoles
PubMed: 24161702
DOI: 10.1016/j.ejmech.2013.10.004 -
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 -
Molecular Diversity Nov 2020A series of benzopyrano[2,3-c]pyrazol-4(2H)-one derivatives were synthesized from readily available 1-phenyl- and 1-methyl-1H-pyrazol-3-ols by sequentially employing...
A series of benzopyrano[2,3-c]pyrazol-4(2H)-one derivatives were synthesized from readily available 1-phenyl- and 1-methyl-1H-pyrazol-3-ols by sequentially employing O-acylation, Fries rearrangement and potassium carbonate-induced cyclization. The anthelmintic properties of the obtained compounds were investigated in vivo in a model nematode, Caenorhabditis elegans. Five compounds, namely 2-phenyl[1]benzopyrano[2,3-c]pyrazol-4(2H)-one 33 and its 7-fluoro, 7-chloro-, 7-bromo- and 8-fluoro-analogues, 36, 38, 40 and 43, respectively, altered the development of C. elegans. While the activities of 33 and 43 were rather modest, compounds 36, 38 and 40 inhibited the growth of the worms at concentrations of approximately 1-3 µM. At these concentrations, the compounds did not kill the worms, but they strongly inhibited their development, with the majority of larvae never progressing past the L1 stage. Moreover, testing in non-cancer human cell lines showed that, with exception of 7-bromo derivative 40, the active compounds have favourable toxicity profiles.
Topics: Animals; Anthelmintics; Caenorhabditis elegans; Cell Line; Cyclization; Humans; Larva; Pyrazoles; Structure-Activity Relationship
PubMed: 31713185
DOI: 10.1007/s11030-019-10010-3 -
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 -
Molecules (Basel, Switzerland) Oct 2021Microwave irradiation has become a popular heating technique in organic synthesis, mainly due to its short reaction times, solventless reactions, and, sometimes, higher... (Review)
Review
Microwave irradiation has become a popular heating technique in organic synthesis, mainly due to its short reaction times, solventless reactions, and, sometimes, higher yields. Additionally, microwave irradiation lowers energy consumption and, consequently, is ideal for optimization processes. Moreover, there is evidence that microwave irradiation can improve the regioselectivity and stereoselectivity aspects of vital importance in synthesizing bioactive compounds. These crucial features of microwave irradiation contribute to its inclusion in green chemistry procedures. Since 2003, the use of microwave-assisted organic synthesis has become common in our laboratory, making our group one of the first Portuguese research groups to implement this heating source in organic synthesis. Our achievements in the transformation of heterocyclic compounds, such as (/)-3-styryl-4-chromen-4-ones, ()-3-(2-hydroxyphenyl)-4-styryl-1-pyrazole, ()-2-(4-arylbut-1-en-3-yn-1-yl)-4-chromen-4-ones, or ()-2-[2-(5-aryl-2-methyl-2-1,2,3-triazol-4-yl)vinyl]-4-chromen-4-ones, will be discussed in this review, highlighting the benefits of microwave irradiation use in organic synthesis.
Topics: Chemistry, Pharmaceutical; Chromones; Combinatorial Chemistry Techniques; Enzyme Inhibitors; Heating; Humans; Microwaves; Molecular Structure; Pyrazoles; Quinolones
PubMed: 34684877
DOI: 10.3390/molecules26206293 -
European Journal of Medicinal Chemistry Feb 2021Methicillin-resistant Staphylococcus aureus (MRSA) is becoming lethal to humanity due to easy transmission and difficult-to-treat skin and flimsy diseases. The most... (Review)
Review
Methicillin-resistant Staphylococcus aureus (MRSA) is becoming lethal to humanity due to easy transmission and difficult-to-treat skin and flimsy diseases. The most threatening aspect is the rapid resistance development of MRSA to any approved antibiotics, including vancomycin. The development of new, efficient, and nontoxic drug candidate to fight against MRSA isolates is the need of the hour. The intriguing molecular structure and versatile bioactive pyrazole core attracting to development required novel antibiotics. This review presents the decade developments of pyrazole-containing derivatives with a broad antibacterial movement against diverged bacterial strains. In specific, we correlated the efficacy of structurally diversified pyrazole analogs against MRSA and discussed different angles of structure-activity relationship (SAR). The current survey highlights pyrazole hybrids' present scenario on MRSA studies, covering articles published from 2011 to 2020. This collective information may become an excellent platform to plan and develop new pyrazole-based small MRSA growth inhibitors with minimal side effects.
Topics: Anti-Bacterial Agents; Dose-Response Relationship, Drug; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Molecular Structure; Pyrazoles; Structure-Activity Relationship
PubMed: 33395624
DOI: 10.1016/j.ejmech.2020.113134 -
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 -
Bioorganic & Medicinal Chemistry Letters Jun 2006We describe a series of pyrazole and isoxazole analogs as antagonists of the alpha(v)beta3 receptor. Compounds showed low to sub-nanomolar potency against alpha(v)beta3,...
We describe a series of pyrazole and isoxazole analogs as antagonists of the alpha(v)beta3 receptor. Compounds showed low to sub-nanomolar potency against alpha(v)beta3, as well as good selectivity against alpha(IIb)beta3. In HT29 cells, most analogs also demonstrated significant selectivity against alpha(v)beta6. Several compounds showed good pharmacokinetic properties in rats, in addition to anti-angiogenic activity in a mouse corneal micropocket model. Compounds were synthesized in a straightforward manner from readily available glutarate precursors.
Topics: Animals; Cell Line; Humans; Integrin alphaVbeta3; Isoxazoles; Mice; Molecular Structure; Pyrazoles; Rats; Structure-Activity Relationship
PubMed: 16621534
DOI: 10.1016/j.bmcl.2006.03.045 -
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