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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) 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 -
Molecules (Basel, Switzerland) Mar 2020The present review presents an overview of antitumor pyrazoles of natural or bioinspired origins. Pyrazole compounds are relatively rare in nature, the first ones having... (Review)
Review
The present review presents an overview of antitumor pyrazoles of natural or bioinspired origins. Pyrazole compounds are relatively rare in nature, the first ones having been reported in 1966 and being essentially used as somniferous drugs. Cytotoxic pyrazoles of natural sources were first isolated in 1969, and a few others have been reported since then, most of them in the last decade. This paper presents a perspective on the current knowledge on antitumor natural pyrazoles, organized into two sections. The first focuses on the three known families of cytotoxic pyrazoles that were directly isolated from plants, for which the knowledge of the medicinal properties is in its infancy. The second section describes pyrazole derivatives of natural products, discussing their structure-activity relationships.
Topics: Animals; Antineoplastic Agents; Biological Products; Biomimetic Materials; Humans; Pyrazoles
PubMed: 32192149
DOI: 10.3390/molecules25061364 -
Molecules (Basel, Switzerland) Aug 2021Pyrazoles are considered privileged scaffolds in medicinal chemistry. Previous reviews have discussed the importance of pyrazoles and their biological activities;... (Review)
Review
Pyrazoles are considered privileged scaffolds in medicinal chemistry. Previous reviews have discussed the importance of pyrazoles and their biological activities; however, few have dealt with the chemistry and the biology of heteroannulated derivatives. Therefore, we focused our attention on recent topics, up until 2020, for the synthesis of pyrazoles, their heteroannulated derivatives, and their applications as biologically active moieties. Moreover, we focused on traditional procedures used in the synthesis of pyrazoles.
Topics: Chemistry Techniques, Synthetic; Humans; Pyrazoles
PubMed: 34443583
DOI: 10.3390/molecules26164995 -
Mini Reviews in Medicinal Chemistry 2022Pyrazoles, an important and well-known class of the azole family, have been found to show a large number of applications in various fields, especially medicinal... (Review)
Review
Pyrazoles, an important and well-known class of the azole family, have been found to show a large number of applications in various fields, especially medicinal chemistry. Pyrazole derivatives, particularly methyl-substituted pyrazoles, have been reported as potent medicinal scaffolds that exhibit a wide spectrum of biological activities. The present review is an attempt to highlight the detailed synthetic approaches for methyl-substituted pyrazoles along with an in-depth analysis of their respective medical significances till March 2021. It is hoped that literature sum-up in the form of present review article would certainly be a great tool in assisting medicinal chemists in generating new leads possessing pyrazole nucleus with high efficacy and less microbial resistance.
Topics: Chemistry, Pharmaceutical; Pyrazoles
PubMed: 34521325
DOI: 10.2174/1389557521666210914124914 -
Medicinal Chemistry (Shariqah (United... 2022Pyrazole scaffolds have gained importance in drug discovery and development for various pharmacological activities like antiviral, antifungal, anticancer,... (Review)
Review
BACKGROUND
Pyrazole scaffolds have gained importance in drug discovery and development for various pharmacological activities like antiviral, antifungal, anticancer, antidepressant, antiinflammatory, antibacterial, etc. Additionally, the pyrazole moiety has shown potent anti-HIV activity as a core heterocycle or substituted heterocycles derivatives (mono, di, tri, tetra, and fused pyrazole derivatives). To assist the development of further potential anti-HIV agents containing pyrazole nucleus, here we have summarized pyrazole containing anti-HIV compounds that have been reported by researchers all over the world for the last two decades.
OBJECTIVE
The present review concentrates on an assortment of pyrazole containing compounds, particularly for potential therapeutic activity against HIV.
METHODS
Google Scholar, Pubmed, and SciFinder were searched databases with ''pyrazol'' keywords. Further, the year of publication and keywords ''Anti-HIV'' filter was applied to obtain relevant reported literature for anti-HIV agents containing pyrazole as a core or substituted derivatives.
RESULTS
This review article has shown the comprehensive compilation of 220 compounds containing pyrazole nucleus and possessing anti-HIV activity by sorting approximately 40 research articles from 2001 to date. 1-(4-Benzoylpiperazin-1-yl)-2-(4-fluoro-7-(1H-pyrazol-3-yl)-1H-pyrrolo[2,3-c]pyridin- 3-yl)ethane-1,2-dione (13), 3-(3-(2-(4-benzoylpiperazin-1-yl)-2-oxoacetyl)-4-fluoro-1H-pyrrolo[2,3- c]pyridin-7-yl)-1H-pyrazole-5-carboxamide (31), 3-(3-(2-(4-benzoylpiperazin-1-yl)-2-oxoacetyl)-4- fluoro-1H-pyrrolo[2,3-c]pyridin-7-yl)-1H-pyrazole-5-carboxamide (88), 3-cyanophenoxypyrazole derivative (130), and 4-(4-chlorophenyl)-5-(4-methyl-5-((4-nitrophenyl)diazenyl)thiazol-2-yl)-3- phenyl-5,6-dihydro-4H-pyrazolo[4,3-d]isoxazole (178) were the most potent mono-, di-, tri-, tetrasubstituted, and fused pyrazole derivatives, respectively, which have shown potent anti-HIV activity among all the described derivatives as compared with standard anti-HIV drugs.
CONCLUSION
This review article provides an overview of the potential therapeutic activity of pyrazole derivatives against HIV that will be helpful for designing pyrazole containing compounds for anti-HIV activity.
Topics: Anti-HIV Agents; Anti-Inflammatory Agents; Antifungal Agents; HIV Infections; Humans; Pyrazoles
PubMed: 34994333
DOI: 10.2174/1573406418666220106163846 -
The Journal of Organic Chemistry Aug 2022Inspired by crystal structures, we designed and achieved a catalyst-free Michael reaction for the preparation of an N1-alkyl pyrazole in a high yield (>90%) with...
Inspired by crystal structures, we designed and achieved a catalyst-free Michael reaction for the preparation of an N1-alkyl pyrazole in a high yield (>90%) with excellent regioselectivity (N1/N2 > 99.9:1). The scope of this protocol has been extended to accomplish the first general regioselective N1-alkylation of 1-pyrazoles to give di-, tri-, and tetra-substituted pyrazoles in a single step. The resulting pyrazoles bear versatile functional groups such as bromo, ester, nitro, and nitrile, offering opportunities for late-stage functionalization. This efficient methodology will have an impact on drug discovery, as several Food and Drug Administration-approved drugs are pyrazole derivatives. A working hypothesis for the regioselectivity is proposed. X-ray crystal structures of the products that highlight the attractive interactions are discussed. This report provides a rare source for the further elucidation of the attractive interactions because the isomeric ratios and the crystal structures are directly related.
Topics: Alkylation; Catalysis; Isomerism; Pyrazoles
PubMed: 35877958
DOI: 10.1021/acs.joc.2c00980 -
Anti-inflammatory & Anti-allergy Agents... 2024Pyrazole is a well-known nucleus in the pharmacy field with a wide range of other activities in addition to anti-inflammatory and analgesic, i.e., anticonvulsant,...
BACKGROUND
Pyrazole is a well-known nucleus in the pharmacy field with a wide range of other activities in addition to anti-inflammatory and analgesic, i.e., anticonvulsant, antiviral, and anticancer activities. There are well-known marketed drugs having pyrazole moiety as celecoxib, and lonazolac as COX-II inhibitors.
AIMS
We aim to synthesize better anti-inflammatory than existing ones. Thiophene is also known for its analgesic and anti-inflammatory action. Thus, the fusion of both gives better anti-inflammatory agents. In the present studies, derivatives from two series of pyrazole were prepared by reacting substituted chalcone (3a-3f) derivatives prepared from 2-acetyl thiophene. They substituted aromatic aldehydes with phenyl hydrazine to form (5a-5f) and with 2, 4-dinitro phenyl hydrazine giving compounds (6a-6f) separately.
METHODS
Purified and characterized pyrazoles have been analyzed for analgesic and anti-inflammatory activities by using standard methods. Compounds 5e, 5f, and 6d were proved to be potent analgesics and series (5a-5f) was found to have anti-inflammatory action, which was further validated using docking and ADME studies.
RESULTS
The ADME profile of synthesized compounds was found to be satisfactory.
CONCLUSION
The synthesized compounds can serve as lead for further drug designing.
Topics: Pyrazoles; Animals; Analgesics; Molecular Docking Simulation; Anti-Inflammatory Agents; Male; Mice; Structure-Activity Relationship; Edema; Humans; Rats; Pain; Rats, Wistar
PubMed: 38828869
DOI: 10.2174/0118715230275741231207115011 -
Angewandte Chemie (International Ed. in... Sep 2021We report the first enantioselective addition of pyrazoles to 1,3-dienes. Secondary and tertiary allylic pyrazoles can be generated with excellent regioselectivity....
We report the first enantioselective addition of pyrazoles to 1,3-dienes. Secondary and tertiary allylic pyrazoles can be generated with excellent regioselectivity. Mechanistic studies support a pathway distinct from previous hydroaminations: a Pd -catalyzed ligand-to-ligand hydrogen transfer (LLHT). This hydroamination tolerates a range of functional groups and advances the field of diene hydrofunctionalization.
Topics: Alkadienes; Catalysis; Ligands; Molecular Structure; Palladium; Pyrazoles; Stereoisomerism
PubMed: 34145705
DOI: 10.1002/anie.202105679 -
Bioorganic Chemistry Dec 2020Convenient structures such as 2,4-diketo esters have been widely used as an effective pattern in medicinal chemistry and pharmacology for drug discovery. 2,4-Diketonate... (Review)
Review
Convenient structures such as 2,4-diketo esters have been widely used as an effective pattern in medicinal chemistry and pharmacology for drug discovery. 2,4-Diketonate is a common scaffold that can be found in many biologically active and naturally occurring compounds. Also, many 2,4-diketo ester derivatives have been prepared due to their suitable synthesis. These synthetic drugs and natural products have shown numerous interesting biological properties with clinical potential as a cure for the broad specter of diseases. This review aims to highlight the important evidence of 2,4-diketo esters as a privileged scaffold in medicinal chemistry and pharmacology. Herein, numerous aspects of 2,4-diketo esters will be summarized, including synthesis and isolation of their derivatives, development of novel synthetic methodologies, the evaluation of their biological properties as well as the mechanisms of action of the diketo ester derivates. This paperwork is expected to be a comprehensive, trustworthy, and critical review of the 2,4-diketo ester intermediate to the chemistry community.
Topics: Acylation; Anti-Infective Agents; Antineoplastic Agents; Antiviral Agents; Chemistry, Pharmaceutical; Esters; Humans; Isoxazoles; Keto Acids; Models, Molecular; Molecular Structure; Pyrazoles; Pyrrolidinones; Structure-Activity Relationship
PubMed: 33086180
DOI: 10.1016/j.bioorg.2020.104343