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Bioconjugate Chemistry Mar 2009The use of long-lifetime emitting lanthanide(III) chelate labels or probes together with time-resolved fluorometry in detection provides a method to generate sensitive... (Review)
Review
The use of long-lifetime emitting lanthanide(III) chelate labels or probes together with time-resolved fluorometry in detection provides a method to generate sensitive bioaffinity assays. However, the use of stable chelates demands very complicated optimization of the chelate structure. A great number of chelates have been synthesized, but usually, only the most prominent structures were then converted to corresponding biomolecule labeling reactants. This review covers the syntheses of luminescent lanthanide chelates comprising a pyridine subunit that allow solution and solid-phase bioconjugation.
Topics: Chelating Agents; Combinatorial Chemistry Techniques; Lanthanoid Series Elements; Luminescent Agents; Pyridines
PubMed: 19072705
DOI: 10.1021/bc800370s -
Bioorganic & Medicinal Chemistry Aug 2014Spirocyclic benzopyrans 2 interact with high affinity and selectivity with σ₁ receptors. Bioisosteric replacement of the benzene ring of the benzopyran substructure...
Spirocyclic benzopyrans 2 interact with high affinity and selectivity with σ₁ receptors. Bioisosteric replacement of the benzene ring of the benzopyran substructure with the electron rich thiophene ring (3) led to increased σ₁ affinity. Herein the synthesis and pharmacological evaluation of electron deficient pyridine bioisosteres 4 are reported. Homologation of the aldehyde 6 to afford the pyridylacetaldehyde derivative 8 was performed by a Wittig reaction. Bromine lithium exchange of the bromopyridine 8, addition to 1-benzylpiperidin-4-one and cyclization led to the spirocyclic pyrranopyridine 10. Hydrogenolytic removal of the N-benzyl moiety of 10 provided the secondary amine 11, which allowed the introduction of various N-substituents (12a-d). Cyclization of the hydroxy acetal 9 with HCl led to various modifications of the substituent in 3'-position. Generally the σ₁ affinity of the pyridine derivatives is reduced compared with those of the benzene and thiophene derivatives 2 and 3. However, the relationships between the structure and the σ₁ affinity follow the same rules as for the benzene and thiophene derivatives. The most promising σ₁ ligand within this class of compounds is the pyranopyridine 15 with a double bond in the pyran ring revealing a Ki-value of 4.6 nM and a very high selectivity (>217-fold) over the σ₂ subtype.
Topics: Animals; Brain; Cyclization; Guinea Pigs; Ligands; Liver; Protein Binding; Protein Isoforms; Pyrans; Pyridines; Rats; Receptors, sigma; Spiro Compounds; Structure-Activity Relationship
PubMed: 24913984
DOI: 10.1016/j.bmc.2014.05.033 -
Molecular Diversity Nov 2009A general review (138 references) focused on the recent advances in the application of Meldrum's acid reactivity for synthesis of diverse pyridine and pyrimidine... (Review)
Review
A general review (138 references) focused on the recent advances in the application of Meldrum's acid reactivity for synthesis of diverse pyridine and pyrimidine derivatives, mostly small and drug-like molecules is presented.
Topics: Dioxanes; History, 19th Century; History, 20th Century; Pyridines; Pyrimidines
PubMed: 19381852
DOI: 10.1007/s11030-009-9136-x -
Toxicology Letters Jun 1996In order to evaluate the possibility that the metabolism of pyridine may be important for its toxic actions, pyridine was compared with pyridine N-oxide,...
In order to evaluate the possibility that the metabolism of pyridine may be important for its toxic actions, pyridine was compared with pyridine N-oxide, 2-hydroxypyridine, 3-hydroxypyridine, 4-hydroxypyridine and pyridinium methyliodide in rats given equal molar doses of the chemicals i.p. Hepatoxicity was assessed by measuring serum sorbitol dehydrogenase, nephrotoxicity by determining increases in blood urea nitrogen and serum creatinine, and influence on xenobiotic metabolism by measuring changes in p-nitrophenol hydroxylase and ethoxyresorufin and benzyloxyresorufin dealkylase activities. After a single dose of 2.5 mmol/kg, pyridinium methyliodide was the only compound that was lethal whereas 2-hydroxypyridine was the only one that caused significant hepatoxicity. Pyridine, pyridine N-oxide, 3-hydroxypyridine and 4-hydroxypyridine were effective inducers of xenobiotic metabolism. Thus the metabolites of pyridine may play a role, either singly or collectively, in the actions of pyridine.
Topics: Analysis of Variance; Animals; Antioxidants; Cytochrome P-450 CYP1A1; Cytochrome P-450 CYP2B1; Cytochrome P-450 Enzyme System; Injections, Intraperitoneal; Kidney; Liver; Male; Oxidoreductases; Poisoning; Pyridines; Pyridinium Compounds; Pyridones; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship
PubMed: 8644130
DOI: 10.1016/0378-4274(96)03660-0 -
European Journal of Medicinal Chemistry Sep 2018It has been reported that benzo [7]annulen-7-amines bearing electron withdrawing substituents such as 3d with a 2-Cl or 3e with a 2-NO moiety show very high affinity...
It has been reported that benzo [7]annulen-7-amines bearing electron withdrawing substituents such as 3d with a 2-Cl or 3e with a 2-NO moiety show very high affinity towards the ifenprodil binding site of GluN2B subunit containing NMDA receptors. Therefore, bioisosteres of 3 with an electron deficient pyridine ring instead of the chloro- or nitrobenzene ring were envisaged. Starting from pyridine-2,3-dicarboxylic acid (5) a five-step synthesis of the key intermediate, the ketone 10, was developed. Reductive amination with various primary amines and NaBH(OAc) led to the homologous secondary amines 11a-c. Subsequent methylation yielded the tertiary amines 12b and 12c. Receptor binding studies with [H]ifenprodil revealed K-values above 100 nM for the most active phenylpropyl- and phenylbutylamines 11b and 11c. The >100-fold reduced GluN2B affinity of pyridines 11b and 11c compared to the GluN2B affinity of the corresponding chloro- and nitrobenzene derivatives 3d and 3e indicates that the pyridine ring is not tolerated as bioisosteric replacement of the chloro- or nitrobenzene ring in this type of compounds.
Topics: Amines; Animals; Cells, Cultured; Dose-Response Relationship, Drug; Guinea Pigs; Mice; Molecular Structure; Polycyclic Compounds; Pyridines; Rats; Receptors, N-Methyl-D-Aspartate; Structure-Activity Relationship
PubMed: 30103189
DOI: 10.1016/j.ejmech.2018.08.003 -
Journal of the American Chemical Society Aug 2022Herein, we report a method for C3-selective C-H tri- and difluoromethylthiolation of pyridines. The method relies on borane-catalyzed pyridine hydroboration for...
Herein, we report a method for C3-selective C-H tri- and difluoromethylthiolation of pyridines. The method relies on borane-catalyzed pyridine hydroboration for generation of nucleophilic dihydropyridines; these intermediates react with trifluoromethylthio and difluoromethylthio electrophiles to form functionalized dihydropyridines, which then undergo oxidative aromatization. The method can be used for late-stage functionalization of pyridine drugs for the generation of new drug candidates.
Topics: Dihydropyridines; Molecular Structure; Pyridines
PubMed: 35913823
DOI: 10.1021/jacs.2c06776 -
Environmental Science and Pollution... Nov 2017Biodegradation of pyridine and quinoline is initiated with mono-oxygenation reactions that require an intracellular electron donor. Simultaneous biodegradation of both...
Biodegradation of pyridine and quinoline is initiated with mono-oxygenation reactions that require an intracellular electron donor. Simultaneous biodegradation of both substrates should set up competition for the intracellular electron donor that may inhibit one or more of the mono-oxygenation steps. An internal circulation baffled biofilm reactor (ICBBR) was used to evaluate the impacts of competition during pyridine and quinoline biodegradation. Compared with independent biodegradation, pyridine and quinoline removal rates were slowed when biodegraded simultaneously, although the pyridine removal rate decreased more than for quinoline. The first mono-oxygenation of quinoline (to 2-hydroxyquinoline) always was faster than the first mono-oxygenation of pyridine (to 2-hydroxypyridine), and the difference was accentuated with pyridine and quinoline which were biodegraded simultaneously due to the competition for intracellular electron donor. Competition also existed between the second mono-oxygenations, and the removal rate of 2-hydroxypyridine was faster than the rate for 2-hydroxyquinoline, even though the rate was faster for quinoline than pyridine. Adding an exogenous electron donor accelerated all mono-oxygenations in proportion to the amount of donor added, but the increments were greater for quinoline due to its higher affinity for intracellular electron donors than pyridine. When actual coking wastewater was used as the background matrix, removals of pyridine and quinoline exhibited the same competitive trends.
Topics: Biodegradation, Environmental; Biofilms; Bioreactors; Electrons; Pyridines; Quinolines
PubMed: 28921046
DOI: 10.1007/s11356-017-0082-3 -
Scientific Reports Dec 2016Pyridinols and pyridinamines are important intermediates with many applications in chemical industry. The pyridine derivatives are in great demand as synthons for...
Pyridinols and pyridinamines are important intermediates with many applications in chemical industry. The pyridine derivatives are in great demand as synthons for pharmaceutical products. Moreover, pyridines are used either as biologically active substances or as building blocks for polymers with unique physical properties. Application of enzymes or whole cells is an attractive strategy for preparation of hydroxylated pyridines since the methods for chemical synthesis of pyridinols, particularly aminopyridinols, are usually limited or inefficient. Burkholderia sp. MAK1 (DSM102049), capable of using pyridin-2-ol as the sole carbon and energy source, was isolated from soil. Whole cells of Burkholderia sp. MAK1 were confirmed to possess a good ability to convert different pyridin-2-amines and pyridin-2-ones into their 5-hydroxy derivatives. Moreover, several methylpyridines as well as methylated pyrazines were converted to appropriate N-oxides. In conclusion, regioselective oxyfunctionalization of pyridine derivatives using whole cells of Burkholderia sp. MAK1 is a promising method for the preparation of various pyridin-5-ols and pyridin-N-oxides.
Topics: Burkholderia; Hydroxylation; Molecular Structure; Pyridines; Soil Microbiology
PubMed: 27982075
DOI: 10.1038/srep39129 -
Zeitschrift Fur Unfallmedizin Und... Jul 1946
Topics: Pyridines
PubMed: 20293950
DOI: No ID Found -
ChemMedChem Jan 2021We demonstrate that a diboration-electrocyclization sequence provides access to a range of pyridine-fused, small-molecule boronic ester building blocks, and that these...
We demonstrate that a diboration-electrocyclization sequence provides access to a range of pyridine-fused, small-molecule boronic ester building blocks, and that these are amenable to high-throughput synthesis leading to biaryl and ether-linked compound libraries. Moreover, the implementation of an integrated physicochemical and ADME profiling workflow allows accelerated design of novel lead compounds for application in drug-discovery projects.
Topics: Automation; Boronic Acids; Drug Design; Esters; Molecular Structure; Pyridines
PubMed: 33241901
DOI: 10.1002/cmdc.202000852