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Journal of Labelled Compounds &... Dec 2019N-labelled pyridines are liquid- and solid-state nuclear magnetic resonance (NMR) probes for chemical and biological environments because their N chemical shifts are...
N-labelled pyridines are liquid- and solid-state nuclear magnetic resonance (NMR) probes for chemical and biological environments because their N chemical shifts are sensitive to hydrogen-bond and protonation states. By variation of the type and number of substituents, different target pyridines can be synthesized exhibiting different pK values and molecular volumes. Various synthetic routes have been described in the literature, starting from different precursors or modification of other N-labelled pyridines. In this work, we have explored the synthesis of N N-labelled pyridines using a two-step process via the synthesis of alkoxy-3,4-dihydro-2H-pyran as precursor exhibiting already the desired pyridine substitution pattern. As an example, we have synthesized 3,5-dimethylpyridine- N (lutidine- N) as demonstrated by N-NMR spectroscopy. That synthesis starts from methacrolein, propenyl ether, and N-labelled NH Cl as nitrogen source.
Topics: Chemistry Techniques, Synthetic; Hydrogen Bonding; Isotope Labeling; Nitrogen Isotopes; Pyridines
PubMed: 31677176
DOI: 10.1002/jlcr.3807 -
Scientific Reports Dec 2020A novel, expedient and effective methodology for the synthesis of distinctly substituted 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine and...
High pressure assisted synthetic approach for novel 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine and 5,6-dihydrobenzo[h]quinoline derivatives and their assessment as anticancer agents.
A novel, expedient and effective methodology for the synthesis of distinctly substituted 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine and 5,6-dihydrobenzo[h]quinoline systems has been developed with a new synthetic platform. This process includes ammonium acetate-mediated cyclocondensation reactions of 3-oxo-2-arylhydrazonopropanals with benzosuberone and tetralone precursors, respectively, using the high-pressure Q-tube reactor, which has been found to be superior to both conventional heating and microwave irradiation. The novel protocol benefits from its high atom efficiency, economy, ease of workup, broad substrate scope and is also applicable to gram-scale synthesis. To identify and confirm the newly synthesized targeted compounds, the X-ray single-crystal as well as all possible spectroscopic methods were utilized. The cytotoxicity of the newly synthesized 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine 4a-j and 5,6-dihydrobenzo-[h]quinolines derivatives 6a-e were preliminary examined toward three cell lines of human cancer; lung cancer (A549), breast cancer (MCF-7) and colon cancer (HCT-116), by applying the MTT colorimetric assay. The achieved results reflected the promising profile of the prepared compounds in this study against cancer cells and have shown that members from the synthesized 6,7-dihydro-5H-benzo[6,7]cyclohepta[1,2-b]pyridine 4a-j exhibited promising cytotoxicity's against MCF-7, and A549 cancer cells respectively, while the HCT-116 (colon) cancer cells were inhibited by certain examples of 5,6-dihydrobenzo[h]quinoline derivatives 6c,d. These promising results could serve as a good primary base for further research into the design of anticancer drugs.
Topics: Antineoplastic Agents; Cell Line, Tumor; Chemistry, Pharmaceutical; Colonic Neoplasms; Crystallography, X-Ray; Cyclization; Drug Design; Heterocyclic Compounds; Humans; Hydroxyquinolines; Pressure; Pyridines; Spectrum Analysis
PubMed: 33303858
DOI: 10.1038/s41598-020-78590-x -
International Journal of Molecular... May 2023Human immunodeficiency virus (HIV) causes one of the most dangerous diseases-acquired immunodeficiency syndrome (AIDS). An estimated about 40 million people are... (Review)
Review
Human immunodeficiency virus (HIV) causes one of the most dangerous diseases-acquired immunodeficiency syndrome (AIDS). An estimated about 40 million people are currently living with HIV worldwide, most of whom are already on antiretroviral therapy. This makes the development of effective drugs to combat this virus very relevant. Currently, one of the dynamically developing areas of organic and medicinal chemistry is the synthesis and identification of new compounds capable of inhibiting HIV-1 integrase-one of the HIV enzymes. A significant number of studies on this topic are published annually. Many compounds inhibiting integrase incorporate pyridine core. Therefore, this review is an analysis of the literature on the methods for the synthesis of pyridine-containing HIV-1 integrase inhibitors since 2003 to the present.
Topics: Humans; HIV Integrase Inhibitors; HIV Integrase; HIV Infections; Pyridines
PubMed: 37298265
DOI: 10.3390/ijms24119314 -
Chembiochem : a European Journal of... Dec 2021Fluoro-substituted and heteroaromatic compounds are valuable intermediates for a variety of applications in pharma- and agrochemistry and synthetic chemistry. This study...
Fluoro-substituted and heteroaromatic compounds are valuable intermediates for a variety of applications in pharma- and agrochemistry and synthetic chemistry. This study investigates the chemoenzymatic preparation of chiral alcohols bearing a heteroaromatic ring with an increasing degree of fluorination in α-position. Starting from readily available picoline derivatives prochiral α-halogenated acyl moieties were introduced with excellent selectivity and 64-95 % yield. The formed carbonyl group was subsequently reduced to the corresponding alcohols using the alcohol dehydrogenase from Lactobacillus kefir, yielding an enantiomeric excess of 95->99 % and up to 98 % yield.
Topics: Alcohol Dehydrogenase; Alcohols; Halogenation; Lactobacillus; Molecular Structure; Pyridines
PubMed: 34520599
DOI: 10.1002/cbic.202100392 -
BioMed Research International 2022Due to the high homology of the ATP sites of the JAK family, the development of selective inhibitors for a certain JAK isoform is extremely challenging. Our strategy to...
Due to the high homology of the ATP sites of the JAK family, the development of selective inhibitors for a certain JAK isoform is extremely challenging. Our strategy to achieve high selectivity for TYK2 relies on targeting the TYK2 pseudokinase (JH2) domain. Based on the clinical compound BMS-986165, through structure-activity relationship studies, a class of acyl compounds with excellent TYK2 inhibitory activity and selectivity to other subtypes of the JAK family was discovered.
Topics: Janus Kinases; Protein Kinase Inhibitors; Pyridines; Structure-Activity Relationship; TYK2 Kinase
PubMed: 35586808
DOI: 10.1155/2022/6383893 -
Molecules (Basel, Switzerland) May 2016The totality of chemical space is so immense that only a small fraction can ever be explored. Computational searching has indicated that bioactivity is associated with a... (Review)
Review
The totality of chemical space is so immense that only a small fraction can ever be explored. Computational searching has indicated that bioactivity is associated with a comparatively small number of ring-containing structures. Pyrrole, indole, pyridine, quinoline, quinazoline and related 6-membered ring-containing aza-arenes figure prominently. This review focuses on the search for fast, efficient and environmentally friendly preparative methods for these rings with specific emphasis on iminyl radical-mediated procedures. Oxime derivatives, particularly oxime esters and oxime ethers, are attractive precursors for these radicals. Their use is described in conventional thermolytic, microwave-assisted and UV-vis based preparative procedures. Photoredox-catalyzed protocols involving designer oxime ethers are also covered. Choice can be made amongst these synthetic strategies for a wide variety of 5- and 6-membered ring heterocycles including phenanthridine and related aza-arenes. Applications to selected natural products and bioactive molecules, including trispheridine, vasconine, luotonin A and rutaecarpine, are included.
Topics: Catalysis; Cyclization; Dioxoles; Free Radicals; Indole Alkaloids; Oximes; Phenanthridines; Pyridines; Pyrroles; Quinazolines; Quinones
PubMed: 27213311
DOI: 10.3390/molecules21050660 -
International Journal of Molecular... Dec 2021The interactions of ions with molecules and the determination of their dissociation patterns are challenging endeavors of fundamental importance for theoretical and...
The interactions of ions with molecules and the determination of their dissociation patterns are challenging endeavors of fundamental importance for theoretical and experimental science. In particular, the investigations on bond-breaking and new bond-forming processes triggered by the ionic impact may shed light on the stellar wind interaction with interstellar media, ionic beam irradiations of the living cells, ion-track nanotechnology, radiation hardness analysis of materials, and focused ion beam etching, deposition, and lithography. Due to its vital role in the natural environment, the pyridine molecule has become the subject of both basic and applied research in recent years. Therefore, dissociation of the gas phase pyridine (CHN) into neutral excited atomic and molecular fragments following protons (H) and dihydrogen cations (H) impact has been investigated experimentally in the 5-1000 eV energy range. The collision-induced emission spectroscopy has been exploited to detect luminescence in the wavelength range from 190 to 520 nm at the different kinetic energies of both cations. High-resolution optical fragmentation spectra reveal emission bands due to the CH(AΔ→XΠ; BΣ→XΠ; CΣ→XΠ) and CN(BΣ→XΣ) transitions as well as atomic H and C lines. Their spectral line shapes and qualitative band intensities are examined in detail. The analysis shows that the H irradiation enhances pyridine ring fragmentation and creates various fragments more pronounced than H cations. The plausible collisional processes and fragmentation pathways leading to the identified products are discussed and compared with the latest results obtained in cation-induced fragmentation of pyridine.
Topics: Computer Simulation; Free Radicals; Hydrogen; Ions; Pyridines; Rotation; Temperature; Vibration
PubMed: 35008633
DOI: 10.3390/ijms23010205 -
Scientific Reports Mar 2015Highly sensitive MR imaging agents that can accurately and rapidly monitor changes in pH would have diagnostic and prognostic value for many diseases. Here, we report an...
Highly sensitive MR imaging agents that can accurately and rapidly monitor changes in pH would have diagnostic and prognostic value for many diseases. Here, we report an investigation of hyperpolarized (15)N-pyridine derivatives as ultrasensitive pH-sensitive imaging probes. These molecules are easily polarized to high levels using standard dynamic nuclear polarization (DNP) techniques and their (15)N chemical shifts were found to be highly sensitive to pH. These probes displayed sharp (15)N resonances and large differences in chemical shifts (Δδ > 90 ppm) between their free base and protonated forms. These favorable features make these agents highly suitable candidates for the detection of small changes in tissue pH near physiological values.
Topics: Contrast Media; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Nitrogen Isotopes; Pyridines
PubMed: 25774436
DOI: 10.1038/srep09104 -
Molecules (Basel, Switzerland) Mar 2021,'-chelate organoboron compounds have been successfully applied in bioimaging, organic light-emitting diodes (OLEDs), functional polymer, photocatalyst,... (Review)
Review
,'-chelate organoboron compounds have been successfully applied in bioimaging, organic light-emitting diodes (OLEDs), functional polymer, photocatalyst, electroluminescent (EL) devices, and other science and technology areas. However, the concise and efficient synthetic methods become more and more significant for material science, biomedical research, or other practical science. Here, we summarized the organoboron-,'-chelate derivatives and showed the different routes of their syntheses. Traditional methods to synthesize ,'-chelate organoboron compounds were mainly using bidentate ligand containing nitrogen reacting with trivalent boron reagents. In this review, we described a series of bidentate ligands, such as bipyridine, 2-(pyridin-2-yl)-1-indole, 2-(5-methyl-1-pyrrol-2-yl)quinoline, -(quinolin-8-yl)acetamide, 1,10-phenanthroline, and diketopyrrolopyrrole (DPP).
Topics: Boron Compounds; Indoles; Isocyanates; Ligands; Phenanthrolines; Pyridines; Quinolines
PubMed: 33807680
DOI: 10.3390/molecules26051401 -
Applied and Environmental Microbiology Aug 20185-Hydroxypicolinic acid (5HPA), a natural pyridine derivative, is microbially degraded in the environment. However, the physiological, biochemical, and genetic...
5-Hydroxypicolinic acid (5HPA), a natural pyridine derivative, is microbially degraded in the environment. However, the physiological, biochemical, and genetic foundations of 5HPA metabolism remain unknown. In this study, an operon (), responsible for 5HPA degradation, was cloned from JQ135. HpaM was a monocomponent flavin adenine dinucleotide (FAD)-dependent monooxygenase and shared low identity (only 28 to 31%) with reported monooxygenases. HpaM catalyzed the decarboxylative hydroxylation of 5HPA, generating 2,5-dihydroxypyridine (2,5DHP). The monooxygenase activity of HpaM was FAD and NADH dependent. The apparent values of HpaM for 5HPA and NADH were 45.4 μM and 37.8 μM, respectively. The genes , , and were found to encode 2,5DHP dioxygenase, -formylmaleamic acid deformylase, and maleamate amidohydrolase, respectively; however, the three genes were not essential for 5HPA degradation in JQ135. Furthermore, the gene , which encodes a maleic acid isomerase, was essential for the metabolism of 5HPA, nicotinic acid, and picolinic acid in JQ135, indicating that it might be a key gene in the metabolism of pyridine derivatives. The genes and proteins identified in this study showed a novel degradation mechanism of pyridine derivatives. Unlike the benzene ring, the uneven distribution of the electron density of the pyridine ring influences the positional reactivity and interaction with enzymes; e.g., the and oxidations are more difficult than the oxidations. Hydroxylation is an important oxidation process for the pyridine derivative metabolism. In previous reports, the hydroxylations of pyridine derivatives were catalyzed by multicomponent molybdenum-containing monooxygenases, while the hydroxylations were catalyzed by monocomponent FAD-dependent monooxygenases. This study identified the new monocomponent FAD-dependent monooxygenase HpaM that catalyzed the decarboxylative hydroxylation of 5HPA. In addition, we found that the gene coding for maleic acid isomerase was pivotal for the metabolism of 5HPA, nicotinic acid, and picolinic acid in JQ135. This study provides novel insights into the microbial metabolism of pyridine derivatives.
Topics: Alcaligenes faecalis; Amidohydrolases; Bacterial Proteins; Biodegradation, Environmental; Flavin-Adenine Dinucleotide; Hydroxylation; Kinetics; Mixed Function Oxygenases; Operon; Phylogeny; Pyridines
PubMed: 29802182
DOI: 10.1128/AEM.00910-18