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Bioorganic & Medicinal Chemistry Letters Apr 2021Pyridones have been utilized as privileged scaffolds in drug discovery. Some of the important roles where this class of heterocycles have found utility in medicinal... (Review)
Review
Pyridones have been utilized as privileged scaffolds in drug discovery. Some of the important roles where this class of heterocycles have found utility in medicinal chemistry include the ability to 1) serve both as a hydrogen bond acceptor and/or a donor; 2) act as a bioisostere for amides, phenyls, pyridines and other nitrogen- or oxygen-containing heterocycles; and 3) impact a target drug molecule's lipophilicity, aqueous solubility and metabolic stability. Detailed discussions of recent advances in their utilization as nonpeptidic mimics and as kinase hinge binding motifs are included. Selected literature examples published from the past twenty years where pyridones have been employed as bioisosteres for phenyls, pyridines, pyridine N-oxides and phenol rings are provided. In addition, this review summarizes the current understanding of possible reactive metabolites related to the pyridone structure.
Topics: Chemistry, Pharmaceutical; Drug Discovery; Molecular Structure; Pyridones
PubMed: 33609656
DOI: 10.1016/j.bmcl.2021.127849 -
Journal of Proteomics Apr 2022
Topics: Electrophoresis, Polyacrylamide Gel; Pyridines; Technology
PubMed: 35240499
DOI: 10.1016/j.jprot.2022.104540 -
Molecules (Basel, Switzerland) Oct 2022Monoterpene pyridine alkaloids (MTPAs) are alkaloids derived from iridoid glycosides (IGs). The common molecular structure of MTPAs is the pyridine ring, while some of... (Review)
Review
Monoterpene pyridine alkaloids (MTPAs) are alkaloids derived from iridoid glycosides (IGs). The common molecular structure of MTPAs is the pyridine ring, while some of them have a cyclopenta[c]pyridine skeleton. Some compounds containing this structure are potentially bioactive medicinal agents. In this paper, seven drug candidates (-), ninety natural source products (-), thirty-seven synthesized compounds (-), as well as twenty-six key intermediates (-) were summarized. We categorized five types of MTPAs and one type of cyclopenta[c]pyridine alkaloids in all. Additionally, their possible genetic pathways were proposed. Then, the chemical transformation, biotransformation, chemical synthesis, as well as the bioactivity of MTPAs and cyclopenta[c]pyridine derivatives were analyzed and summarized. Cyclopenta[c]pyridine derivatives can be concisely and chirally synthesized, and they have shown potentials with antibacterial, insecticidal, antiviral, anti-inflammatory, and neuropharmacological activities.
Topics: Monoterpenes; Alkaloids; Molecular Structure; Pyridines; Biological Products
PubMed: 36364013
DOI: 10.3390/molecules27217187 -
International Journal of Molecular... May 2022In the context of the new life-threatening COVID-19 pandemic caused by the SARS-CoV-2 virus, finding new antiviral and antimicrobial compounds is a priority in current... (Review)
Review
In the context of the new life-threatening COVID-19 pandemic caused by the SARS-CoV-2 virus, finding new antiviral and antimicrobial compounds is a priority in current research. Pyridine is a privileged nucleus among heterocycles; its compounds have been noted for their therapeutic properties, such as antimicrobial, antiviral, antitumor, analgesic, anticonvulsant, anti-inflammatory, antioxidant, anti-Alzheimer's, anti-ulcer or antidiabetic. It is known that a pyridine compound, which also contains a heterocycle, has improved therapeutic properties. The singular presence of the pyridine nucleus, or its one together with one or more heterocycles, as well as a simple hydrocarbon linker, or grafted with organic groups, gives the key molecule a certain geometry, which determines an interaction with a specific protein, and defines the antimicrobial and antiviral selectivity for the target molecule. Moreover, an important role of pyridine in medicinal chemistry is to improve water solubility due to its poor basicity. In this article, we aim to review the methods of synthesis of pyridine compounds, their antimicrobial and antiviral activities, the correlation of pharmaceutical properties with various groups present in molecules as well as the binding mode from Molecular Docking Studies.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Antiviral Agents; Humans; Molecular Docking Simulation; Pandemics; Pyridines; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 35628466
DOI: 10.3390/ijms23105659 -
Molecules (Basel, Switzerland) Mar 2022Derivatives based on pyridine-2-6- and furan-2,5-dicarboxamide scaffolds reveal numerous chemical properties and biological activities. This fact makes them an exciting...
Derivatives based on pyridine-2-6- and furan-2,5-dicarboxamide scaffolds reveal numerous chemical properties and biological activities. This fact makes them an exciting research topic in supramolecular and coordination chemistry and in discovering new pharmacologically-active compounds. This work aimed to obtain a series of symmetrical pyridine-2-6- and furan-2,5-dicarboxamides through a condensation reaction of the appropriate acyl chlorides and aromatic amides. Successful syntheses were confirmed with NMR spectroscopy. We solved their crystal structures for seven compounds; two pyridine and five furan derivatives. Based on our crystallographic studies, we were able to indicate supramolecular features of the crystals under investigation. Additionally, Hirshfeld surface analysis allowed us to calculate a distribution of intermolecular contacts in the dicarboxamide crystals.
Topics: Amides; Furans; Magnetic Resonance Spectroscopy; Pyridines
PubMed: 35335183
DOI: 10.3390/molecules27061819 -
Mini Reviews in Medicinal Chemistry 2021Heterocyclic compounds play a critical role in medicinal chemistry, and many available drugs contain heterocyclic rings. A six-membered heterocyclic compound, pyridine,... (Review)
Review
Heterocyclic compounds play a critical role in medicinal chemistry, and many available drugs contain heterocyclic rings. A six-membered heterocyclic compound, pyridine, showed various applications, including being an important solvent, reagent, and precursor in agrochemicals and pharmaceuticals. Due to the increase in drug resistance, there is an apparent medical need to develop new antiviral agents. Various derivatives of pyridine scaffold display broad biological activities such as anti-microbial, antiviral, antioxidant, anti-diabetic, anti-cancer, anti-malarial, analgesic, and antiinflammatory activities. Furthermore, they display psychopharmacological, antagonistic, anti-amoebic agents, and anti-thrombic activities. Due to the high importance of pyridine derivatives, in the present review, we tried to collect and classify many pyridine derivatives based on their structures from 2000 to 2020. Pyridine derivatives were classified into two general categories, including pyridine containing heterocycles and pyridine fused rings. The structure-activity relationship (SAR) and the action mechanism of derivatives were also investigated. According to the recent studies, these derivatives exhibited good antiviral activity against different types of viruses such as the human immunodeficiency viruses (HIV), the hepatitis C virus (HCV), the hepatitis B virus (HBV), respiratory syncytial virus (RSV), and cytomegalovirus (CMV). These derivatives inhibited viral application with different action mechanism such as RT inhibition, polymerase inhibition, inhibition of RNase H activity, inhibition of maturation, inhibition of the viral thymidine kinase, AAK1 (Adaptor-Associated Kinase 1) inhibition, GAK (Cyclin G-associated kinase) inhibition, inhibition of post-integrational event, inhibition of HDAC6, CCR5 antagonistic activity, DNA and RNA replication inhibition, gene expression inhibition, cellular NF-jB signaling pathway and neuraminidase (NA) inhibition, protein synthesis inhibition, and generally inhibition of viral replication cycle. This paper summarized the past and present results about the discovery of novel lead compounds with good antiviral activity. Studies exhibited that almost all of the evaluations were performed by way of in vitro testing. It is necessary to investigate in vivo and clinical testing for better evaluations in the future. We believe that pyridine derivatives can be used as promising antiviral agents and more broad investigations in this field need to be performed.
Topics: Animals; Antiviral Agents; Humans; Pyridines
PubMed: 33573543
DOI: 10.2174/1389557521666210126143558 -
Journal of Pharmaceutical and... May 2023A sensitive, accurate and precise liquid chromatography (LC) method for the simultaneous determination of ceftazidime and pyridine in human plasma has been developed and... (Review)
Review
A sensitive, accurate and precise liquid chromatography (LC) method for the simultaneous determination of ceftazidime and pyridine in human plasma has been developed and validated. Acetonitrile (ACN) was employed to precipitate the proteins in the plasma samples. Chromatographic separation was performed with a Kinetex® C18 (150 mm × 3 mm, 2.6 µm) column with gradient elution. Ammonium formate 20 mM and ACN were mixed in a ratio of 98:2 (v/v) for mobile phase A and 85:15 (v/v) for mobile phase B. Both were adjusted to pH 4.5 with formic acid. The flow rate was 0.4 mL/min. UV detection was performed at 254 nm. Calibration curves were linear in the range from 0.3 to 225 μg/mL for ceftazidime and from 0.2 to 10 μg/mL for pyridine with correlation coefficients ≥ 0.999. Within- and between-run precision and accuracy were satisfactory with coefficients of variation (CV) ≤ 8.0% and deviations ≤ 7.0%, respectively. The method fulfilled all validation criteria prescribed by the European Medicines Agency guidelines. Next, it has been used successfully to analyze plasma samples of patients who received ceftazidime under intermittent and continuous administration. With intermittent administration, the concentration of the antibiotics reached a peak and then dropped quickly, which may be below the minimal inhibitory concentration (MIC). With continuous administration, the concentration of the antibiotics remained stable over 24 h, certainly above the MIC. Although the same tendency in ceftazidime concentration changes over time was observed, a difference in concentration amongst the patients was noticeable. The concentration of pyridine in plasma was negligible.
Topics: Humans; Anti-Bacterial Agents; Ceftazidime; Chromatography, High Pressure Liquid; Chromatography, Liquid; Pharmaceutical Preparations; Pyridines; Reproducibility of Results
PubMed: 36858005
DOI: 10.1016/j.jpba.2023.115319 -
Journal of the American Chemical Society Oct 2022A longstanding challenge in fundamental functional group interconversion has been the direct transformation of benzene into pyridine via nitrogen insertion and carbon...
A longstanding challenge in fundamental functional group interconversion has been the direct transformation of benzene into pyridine via nitrogen insertion and carbon deletion. Herein, we report a protocol for the transformation of aryl azides, easily accessible from their corresponding anilines, to 2-aminopyridines using blue light and oxygen. Mechanistic studies corroborate that the arene to pyridine conversion is achieved by nitrogen insertion into the benzene ring followed by oxidative carbon extrusion.
Topics: Aminopyridines; Aniline Compounds; Azides; Benzene; Carbon; Nitrogen; Oxygen; Pyridines
PubMed: 36135802
DOI: 10.1021/jacs.2c08464 -
Current Pharmaceutical Design 2024The escalation of cancer worldwide is one of the major causes of economy burden and loss of human resources. According to the American Cancer Society, there will be... (Review)
Review
BACKGROUND
The escalation of cancer worldwide is one of the major causes of economy burden and loss of human resources. According to the American Cancer Society, there will be 1,958,310 new cancer cases and 609,820 projected cancer deaths in 2023 in the United States. It is projected that by 2040, the burden of global cancer is expected to rise to 29.5 million per year, causing a death toll of 16.4 million. The hemostasis regulation by cellular protein synthesis and their targeted degradation is required for normal cell growth. The imbalance in hemostasis causes unbridled growth in cells and results in cancer. The DNA of cells needs to be targeted by chemotherapeutic agents for cancer treatment, but at the same time, their efficacy and toxicity also need to be considered for successful treatment.
OBJECTIVE
The objective of this study is to review the published work on pyrrole and pyridine, which have been prominent in the diagnosis and possess anticancer activity, to obtain some novel lead molecules of improved cancer therapeutic.
METHODS
A literature search was carried out using different search engines, like Sci-finder, Elsevier, ScienceDirect, RSC etc., for small molecules based on pyrrole and pyridine helpful in diagnosis and inducing apoptosis in cancer cells. The research findings on the application of these compounds from 2018-2023 were reviewed on a variety of cell lines, such as breast cancer, liver cancer, epithelial cancer, etc. Results: In this review, the published small molecules, pyrrole and pyridine and their derivatives, which have roles in the diagnosis and treatment of cancers, were discussed to provide some insight into the structural features responsible for diagnosis and treatment. The analogues with the chromeno-furo-pyridine skeleton showed the highest anticancer activity against breast cancer. The compound 5-amino-N-(1-(pyridin-4- yl)ethylidene)-1H-pyrazole-4-carbohydrazides was highly potent against HEPG2 cancer cell. Redaporfin is used for the treatment of cholangiocarcinoma, biliary tract cancer, cisplatin-resistant head and neck squamous cell carcinoma, and pigmentation melanoma, and it is in clinical trials for phase II. These structural features present a high potential for designing novel anticancer agents for diagnosis and drug development.
CONCLUSION
Therefore, the N- and C-substituted pyrrole and pyridine-based novel privileged small Nheterocyclic scaffolds are potential molecules used in the diagnosis and treatment of cancer. This review discusses the reports on the synthesis of such molecules during 2018-2023. The review mainly discusses various diagnostic techniques for cancer, which employ pyrrole and pyridine heterocyclic scaffolds. Furthermore, the anticancer activity of N- and C-substituted pyrrole and pyridine-based scaffolds has been described, which works against different cancer cell lines, such as MCF-7, A549, A2780, HepG2, MDA-MB-231, K562, HT- 29, Caco-2 cells, Hela, Huh-7, WSU-DLCL2, HCT-116, HBL-100, H23, HCC827, SKOV3, etc. This review will help the researchers to obtain a critical insight into the structural aspects of pyrrole and pyridine-based scaffolds useful in cancer diagnosis as well as treatment and design pathways to develop novel drugs in the future.
Topics: Humans; Neoplasms; Antineoplastic Agents; Pyridines; Pyrroles; Heterocyclic Compounds; Animals
PubMed: 38711394
DOI: 10.2174/0113816128280082231205071504 -
Molecules (Basel, Switzerland) Mar 2022Pyrazolo[3,4-]pyridines are a group of heterocyclic compounds presenting two possible tautomeric forms: the 1- and 2-isomers. More than 300,000 1-pyrazolo[3,4-]pyridines... (Review)
Review
Pyrazolo[3,4-]pyridines are a group of heterocyclic compounds presenting two possible tautomeric forms: the 1- and 2-isomers. More than 300,000 1-pyrazolo[3,4-]pyridines have been described which are included in more than 5500 references (2400 patents) up to date. This review will cover the analysis of the diversity of the substituents present at positions N1, C3, C4, C5, and C6, the synthetic methods used for their synthesis, starting from both a preformed pyrazole or pyridine, and the biomedical applications of such compounds.
Topics: Pyridines
PubMed: 35408636
DOI: 10.3390/molecules27072237