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Molecules (Basel, Switzerland) Oct 2017Chromones, six-membered oxygen heterocycles, and pyrazoles, five-membered two-adjacent-nitrogen-containing heterocycles, represent two important classes of biologically... (Review)
Review
Chromones, six-membered oxygen heterocycles, and pyrazoles, five-membered two-adjacent-nitrogen-containing heterocycles, represent two important classes of biologically active compounds. Certain derivatives of these scaffolds play an important role in medicinal chemistry and have been extensively used as versatile building blocks in organic synthesis. In this context, we will discuss the most relevant advances on the chemistry that involves both chromone and pyrazole rings. The methods reviewed include the synthesis of chromone-pyrazole dyads, synthesis of chromone-pyrazole-fused compounds, and chromones as starting materials in the synthesis of 3(5)-(2-hydroxyaryl)pyrazoles, among others. This review will cover the literature on the chromone and pyrazole dual chemistry and their outcomes in the 21st century.
Topics: Antineoplastic Agents; Chromones; Drug Design; Humans; Molecular Structure; Pyrazoles; Structure-Activity Relationship
PubMed: 28981465
DOI: 10.3390/molecules22101665 -
Future Medicinal Chemistry Mar 2022Bacterial resistance to antibiotics threatens our progress in healthcare, modern medicine, food production and ultimately life expectancy. Antibiotic resistance is a... (Review)
Review
Bacterial resistance to antibiotics threatens our progress in healthcare, modern medicine, food production and ultimately life expectancy. Antibiotic resistance is a global concern, which spreads rapidly across borders and continents due to rapid travel of people, animals and goods. Derivatives of metabolically stable pyrazole nucleus are known for their wide range of pharmacological properties, including antibacterial activities. This review highlights recent reports of pyrazole derivatives targeting different bacterial strains focusing on the drug-resistant variants. Pyrazole derivatives target different metabolic pathways of both Gram-positive and Gram-negative bacteria.
Topics: Alkyl and Aryl Transferases; Anti-Bacterial Agents; Cell Wall; DNA Gyrase; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Positive Bacteria; Pyrazoles; Tetrahydrofolate Dehydrogenase
PubMed: 35050719
DOI: 10.4155/fmc-2021-0275 -
Molecules (Basel, Switzerland) Jan 2018Pyrazole and its derivatives are considered a pharmacologically important active scaffold that possesses almost all types of pharmacological activities. The presence of... (Review)
Review
Pyrazole and its derivatives are considered a pharmacologically important active scaffold that possesses almost all types of pharmacological activities. The presence of this nucleus in pharmacological agents of diverse therapeutic categories such as celecoxib, a potent anti-inflammatory, the antipsychotic CDPPB, the anti-obesity drug rimonabant, difenamizole, an analgesic, betazole, a H2-receptor agonist and the antidepressant agent fezolamide have proved the pharmacological potential of the pyrazole moiety. Owing to this diversity in the biological field, this nucleus has attracted the attention of many researchers to study its skeleton chemically and biologically. This review highlights the different synthesis methods and the pharmacological properties of pyrazole derivatives. Studies on the synthesis and biological activity of pyrazole derivatives developed by many scientists around the globe are reported.
Topics: Animals; Anti-HIV Agents; Anti-Inflammatory Agents; Anti-Obesity Agents; Antidepressive Agents; Antipsychotic Agents; Chemistry, Pharmaceutical; Drug Design; Humans; Pyrazoles
PubMed: 29329257
DOI: 10.3390/molecules23010134 -
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 -
Molecules (Basel, Switzerland) Dec 2020The pyrazole nucleus and its reduced forms, pyrazolines and pyrazolidine, are privileged scaffolds in medicinal chemistry due to their remarkable biological activities.... (Review)
Review
The pyrazole nucleus and its reduced forms, pyrazolines and pyrazolidine, are privileged scaffolds in medicinal chemistry due to their remarkable biological activities. A huge number of pyrazole derivatives have been studied and reported over time. This review article gives an overview of pyrazole derivatives that contain a styryl (2-arylvinyl) group linked in different positions of the pyrazole backbone. Although there are studies on the synthesis of styrylpyrazoles dating back to the 1970s and even earlier, this type of compound has rarely been studied. This timely review intends to summarize the properties, biological activity, methods of synthesis and transformation of styrylpyrazoles; thus, highlighting the interest and huge potential for application of this kind of compound.
Topics: Animals; Humans; Molecular Structure; Pyrazoles
PubMed: 33322752
DOI: 10.3390/molecules25245886 -
Molecules (Basel, Switzerland) Jul 2022Pyrazole and its derivatives are considered a privileged -heterocycle with immense therapeutic potential. Over the last few decades, the pot, atom, and step economy... (Review)
Review
Pyrazole and its derivatives are considered a privileged -heterocycle with immense therapeutic potential. Over the last few decades, the pot, atom, and step economy (PASE) synthesis of pyrazole derivatives by multicomponent reactions (MCRs) has gained increasing popularity in pharmaceutical and medicinal chemistry. The present review summarizes the recent developments of multicomponent reactions for the synthesis of biologically active molecules containing the pyrazole moiety. Particularly, it covers the articles published from 2015 to date related to antibacterial, anticancer, antifungal, antioxidant, α-glucosidase and α-amylase inhibitory, anti-inflammatory, antimycobacterial, antimalarial, and miscellaneous activities of pyrazole derivatives obtained exclusively via an MCR. The reported analytical and activity data, plausible synthetic mechanisms, and molecular docking simulations are organized in concise tables, schemes, and figures to facilitate comparison and underscore the key points of this review. We hope that this review will be helpful in the quest for developing more biologically active molecules and marketed drugs containing the pyrazole moiety.
Topics: Anti-Bacterial Agents; Antifungal Agents; Chemistry, Pharmaceutical; Molecular Docking Simulation; Pyrazoles; alpha-Glucosidases
PubMed: 35897899
DOI: 10.3390/molecules27154723 -
European Journal of Pharmaceutical... Apr 2023Malaria poses a severe public health risk and a significant economic burden in disease-endemic countries. One of the most severe issues in malaria control is the... (Review)
Review
Malaria poses a severe public health risk and a significant economic burden in disease-endemic countries. One of the most severe issues in malaria control is the development of drug resistance in malaria parasites. The standard treatment for malaria is artemisinin-combination therapy (ACT). Nevertheless, the Plasmodium parasite's extensive resistance to prior drugs and reduced ACT efficiency necessitates novel drug discovery. The progress in discovering novel, affordable, and effective antimalarial agents is significant in combating drug resistance, and the hybrid drug concept can be used to covalently link two or more active pharmacophores that may act on multiple targets. Pyrazole and pyrazoline derivatives are considered pharmacologically necessary active heterocyclic scaffolds that possess almost all types of pharmacological activities. This review summarized recent progress in antimalarial activities of synthesized pyrazole and pyrazoline derivatives. The studies published since 2000 are included in this systematic review. This review is anticipated to be beneficial for future study and new ideas in searching for rational development strategies for more effective pyrazole and pyrazoline derivatives as antimalarial drugs.
Topics: Humans; Antimalarials; Malaria; Pyrazoles; Drug Resistance; Folic Acid Antagonists; Plasmodium falciparum
PubMed: 36563914
DOI: 10.1016/j.ejps.2022.106365 -
Molecules (Basel, Switzerland) Dec 2022Pyrazole, an important pharmacophore and a privileged scaffold of immense significance, is a five-membered heterocyclic moiety with an extensive therapeutic profile,... (Review)
Review
Pyrazole, an important pharmacophore and a privileged scaffold of immense significance, is a five-membered heterocyclic moiety with an extensive therapeutic profile, viz., anti-inflammatory, anti-microbial, anti-anxiety, anticancer, analgesic, antipyretic, etc. Due to the expansion of pyrazolecent red pharmacological molecules at a quicker pace, there is an urgent need to put emphasis on recent literature with hitherto available information to recognize the status of this scaffold for pharmaceutical research. The reported potential pyrazole-containing compounds are highlighted in the manuscript for the treatment of cancer and inflammation, and the results are mentioned in % inhibition of inflammation, % growth inhibition, IC, etc. Pyrazole is an important heterocyclic moiety with a strong pharmacological profile, which may act as an important pharmacophore for the drug discovery process. In the struggle to cultivate suitable anti-inflammatory and anticancer agents, chemists have now focused on pyrazole biomolecules. This review conceals the recent expansion of pyrazole biomolecules as anti-inflammatory and anticancer agents with an aim to provide better correlation among different research going around the world.
Topics: Humans; Anti-Inflammatory Agents; Drug Design; Pyrazoles; Antineoplastic Agents; Inflammation; Structure-Activity Relationship; Neoplasms
PubMed: 36557840
DOI: 10.3390/molecules27248708 -
Molecules (Basel, Switzerland) Jun 2021The five-membered heterocyclic group of pyrazoles/pyrazolines plays important role in drug discovery. Pyrazoles and pyrazolines present a wide range of biological...
The five-membered heterocyclic group of pyrazoles/pyrazolines plays important role in drug discovery. Pyrazoles and pyrazolines present a wide range of biological activities. The synthesis of the pyrazolines and pyrazole derivatives was accomplished the condensation of the appropriate substituted aldehydes and acetophenones, suitable chalcones and hydrazine hydrate in absolute ethanol in the presence of drops of glacial acetic acid. The compounds are obtained in good yields 68-99% and their structure was confirmed using IR, H-NMR, C-NMR and elemental analysis. The novel derivatives were studied for their antioxidant, anti-lipid peroxidation (AAPH) activities and inhibitory activity of lipoxygenase. Both classes strongly inhibit lipid peroxidation. Compound was the most potent lipoxygenase inhibitor (IC = 80 µM). The inhibition of the carrageenin-induced paw edema (CPE) and nociception was also determined, with compounds and being the most potent. Compound inhibited nociception higher than . Pyrazoline was found to be active in a preliminary test, for the investigation of anti-adjuvant-induced disease (AID) activity. Pyrazoline derivatives were found to be more potent than pyrazoles. Docking studies of the most potent LOX inhibitor highlight hydrophobic interactions with VAL126, PHE143, VAL520 and LYS526 and a halogen bond between the chlorine atom and ARG182.
Topics: Animals; Anti-Inflammatory Agents; Inhibitory Concentration 50; Lipid Peroxidation; Lipoxygenase; Lipoxygenase Inhibitors; Models, Molecular; Molecular Docking Simulation; Molecular Structure; Protein Binding; Pyrazoles; Rats
PubMed: 34198914
DOI: 10.3390/molecules26113439 -
International Journal of Molecular... Aug 2023Pyrazole derivatives, as a class of heterocyclic compounds, possess unique chemical structures that confer them with a broad spectrum of pharmacological activities. They... (Review)
Review
Pyrazole derivatives, as a class of heterocyclic compounds, possess unique chemical structures that confer them with a broad spectrum of pharmacological activities. They have been extensively explored for designing potent and selective anticancer agents. In recent years, numerous pyrazole derivatives have been synthesized and evaluated for their anticancer potential against various cancer cell lines. Structure-activity relationship studies have shown that appropriate substitution on different positions of the pyrazole ring can significantly enhance anticancer efficacy and tumor selectivity. It is noteworthy that many pyrazole derivatives have demonstrated multiple mechanisms of anticancer action by interacting with various targets including tubulin, EGFR, CDK, BTK, and DNA. Therefore, this review summarizes the current understanding on the structural features of pyrazole derivatives and their structure-activity relationships with different targets, aiming to facilitate the development of potential pyrazole-based anticancer drugs. We focus on the latest research advances in anticancer activities of pyrazole compounds reported from 2018 to present.
Topics: Antineoplastic Agents; Pyrazoles; Cell Line; Structure-Activity Relationship; Tubulin
PubMed: 37628906
DOI: 10.3390/ijms241612724