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Molecular Diversity Apr 2023Two new categories of fused pyridines include 2H-thiazolo[3,2-a]pyridine-6-carbohydrazides and 2H-oxazolo[3,2-a]pyridine-6-carbohydrazides have been successfully...
Two new categories of fused pyridines include 2H-thiazolo[3,2-a]pyridine-6-carbohydrazides and 2H-oxazolo[3,2-a]pyridine-6-carbohydrazides have been successfully synthesized via five-component cascade reactions using 9-fluorenone, cyanoacetohydrazide, 1,1-bis(methylthio)-2-nitroethene, aromatic aldehydes and cysteamine hydrochloride or ethanol amine as starting materials. This new approach involves a subsequence of key steps: N,S-acetal or N,O-acetal formation, Knoevenagel condensation, Michael addition, tautomerization and N-cyclization. It also has some advantages, such as convenience of operation, tolerance of a wide diversity of functional groups, use of green solvent and ease of purification by washing the crude products with ethanol.
Topics: Molecular Structure; Acetals; Pyridines; Ethanol
PubMed: 35587848
DOI: 10.1007/s11030-022-10446-0 -
European Journal of Medicinal Chemistry Nov 2019This article provides an overview of compounds based on imidazo[1,2-a]pyridine, imidazo[1,5-a]pyridine, imidazo[4,5-b]pyridine and imidazo[4,5-c]pyridine scaffolds,... (Review)
Review
This article provides an overview of compounds based on imidazo[1,2-a]pyridine, imidazo[1,5-a]pyridine, imidazo[4,5-b]pyridine and imidazo[4,5-c]pyridine scaffolds, which act as potent ligands of diverse molecular targets localized in the central nervous system. A literature survey revealed that various imidazopyridines can be powerful modulators of several diseases associated with CNS dysfunction including Alzheimer's disease, Parkinson's disease, schizophrenia, depression or sleeping disorders. A description of target enzymes (e.g., β-secretase, γ-secretase, fatty acid amide hydrolase - FAAH, leucine-rich repeat kinase 2 - LRRK2) and selected receptors (e.g., GABA-A, histamine H, serotonin 5-HT, 5-HT, 5-HT, dopamine D, adenosine A, orexin), modes of action of imidazopyridine-based ligands and their therapeutic importance is discussed.
Topics: Animals; Clinical Trials as Topic; Drug Design; Humans; Imidazoles; Ligands; Mental Disorders; Molecular Targeted Therapy; Neurodegenerative Diseases; Pyridines
PubMed: 31404862
DOI: 10.1016/j.ejmech.2019.111569 -
Molecules (Basel, Switzerland) Jun 2021New pyridine, pyrazoloyridine, and furopyridine derivatives substituted with naphthyl and thienyl moieties were designed and synthesized starting from...
New pyridine, pyrazoloyridine, and furopyridine derivatives substituted with naphthyl and thienyl moieties were designed and synthesized starting from 6-(naphthalen-2-yl)-2-oxo-4-(thiophen-2-yl)-1,2-dihydropyridine-3-carbonitrile (). The chloro, methoxy, cholroacetoxy, imidazolyl, azide, and arylamino derivatives were prepared to obtain the pyridine- functionalized derivatives. The derived pyrazolpyridine--glycosides were synthesized via heterocyclization of the -thioxopyridine derivative followed by glycosylation using glucose and galactose. The furopyridine derivative and the tricyclic pyrido[3',2':4,5]furo[3,2-d]pyrimidine were prepared via heterocyclization of the ester derivative followed by a reaction with formamide. The newly synthesized compounds were evaluated for their ability to in vitro inhibit the CDK2 enzyme. In addition, the cytotoxicity of the compounds was tested against four different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549). The CDK2/cyclin A2 enzyme inhibitory results revealed that pyridone , 2-chloro-6-(naphthalen-2-yl)-4-(thiophen-2-yl)nicotinonitrile (), 6-(naphthalen-2-yl)-4-(thiophen-2-yl)-1-pyrazolo[3,4-b]pyridin-3-amine (), S-(3-cyano-6-(naphthaen-2-yl)-4-(thiophen-2-yl)pyridin-2-yl) 2-chloroethanethioate (), and ethyl 3-amino-6-(naphthalen-2-yl)-4-(thiophen-2-yl)furo[2,3-b]pyridine-2-carboxylate () are among the most active inhibitors with IC values of 0.57, 0.24, 0.65, 0.50, and 0.93 µM, respectively, compared to roscovitine (IC 0.394 μM). Most compounds showed significant inhibition on different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549) with IC ranges of 31.3-49.0, 19.3-55.5, 22.7-44.8, and 36.8-70.7 μM, respectively compared to doxorubicin (IC 40.0, 64.8, 24.7 and 58.1 µM, respectively). Furthermore, a molecular docking study suggests that most of the target compounds have a similar binding mode as a reference compound in the active site of the CDK2 enzyme. The structural requirements controlling the CDK2 inhibitory activity were determined through the generation of a statistically significant 2D-QSAR model.
Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Cyclin-Dependent Kinase 2; Dose-Response Relationship, Drug; Doxorubicin; Drug Design; Drug Screening Assays, Antitumor; Humans; Imidazoles; Inhibitory Concentration 50; Molecular Docking Simulation; Protein Kinase Inhibitors; Pyrazoles; Pyridines; Pyrimidines; Quantitative Structure-Activity Relationship
PubMed: 34206976
DOI: 10.3390/molecules26133923 -
Yakugaku Zasshi : Journal of the... 2019New meta-arylene ethynylene foldamers were developed by employing pyridine and phenol units. These demonstrated interesting properties related to the hydrogen-bonding... (Review)
Review
New meta-arylene ethynylene foldamers were developed by employing pyridine and phenol units. These demonstrated interesting properties related to the hydrogen-bonding behavior of the arylene units. Pyridine-acetylene-phenol foldamers showed improved saccharide recognition abilities compared with pyridine-acetylene foldamers with no phenol units. Solid-liquid extraction could be achieved due to the strong binding. Hydrocarbon stapling by alkene metathesis under templation was attempted, and the helical structure was efficiently stabilized. Phenol-acetylene oligomers spontaneously formed helical structures via intramolecular hydrogen bonding. The helical sense could be biased by adding chiral amines.
Topics: Acetylene; Alkenes; Glucose; Hydrocarbons; Hydrogen Bonding; Macromolecular Substances; Molecular Conformation; Monosaccharides; Organic Chemistry Phenomena; Phenol; Pyridines; Solid Phase Extraction
PubMed: 30930394
DOI: 10.1248/yakushi.18-00179-2 -
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 -
Molecules (Basel, Switzerland) Oct 2018An efficient Ag/pyridine co-mediated oxidative arylthiocyanation of activated alkenes via radical addition/cyclization cascade process was developed. This reaction could...
An efficient Ag/pyridine co-mediated oxidative arylthiocyanation of activated alkenes via radical addition/cyclization cascade process was developed. This reaction could be carried out under mild conditions to provide biologically interesting 3-alkylthiocyanato-2-oxindoles in good to excellent yields. Mechanistic studies suggested a unique NCS• radical addition path and clarified the dual roles of catalytic pyridine as base and crucial ligand to accelerate the oxidation of Ag(I) to Ag(II), which is likely oxidant responsible for the formation of NCS• radical. These mechanistic results may impact the design and refinement of other radical based reactions proceeding through catalytic oxidations mediated by Ag(I)-pyridine/persulfate. The chemical versatility of thiocyanate moiety was also highlighted via SCN-tailoring chemistry in post-synthetic transformation for new S-C(sp³/sp²/sp), S-P, and S-S bonds constructions. The protocol provides an easy access to many important bioisosteres in medicinal chemistry and an array of sulfur-containing 2-oxindoles that are difficult to prepare by other approaches.
Topics: Alkenes; Magnetic Resonance Spectroscopy; Molecular Structure; Oxidation-Reduction; Pyridines; Silver; Thiocyanates
PubMed: 30360416
DOI: 10.3390/molecules23102727 -
Chemistry & Biodiversity Jun 2023In this project, an effective procedure for constructing a new combination of pyrazolo[3,4-b]pyridine was depicted through the coupling of diazonium salt 2 of...
In this project, an effective procedure for constructing a new combination of pyrazolo[3,4-b]pyridine was depicted through the coupling of diazonium salt 2 of heterocyclic amine 1 with active methylene, enamine, and amidine moieties such as 3, 5, 7, and 9 at 0-5 °C in pyridine to afford hydrazinylhydrazonoyl derivatives 4, and diazenylheterocyclic derivatives 6, 8, and 10, respectively. Also, aminopyrazolo[3,4-b]pyridine 1 condensed with different aryl or heteroaryl aldehydes in EtOH/AcOH gave the corresponding aldimine 14, 15, 16. Compound 15 was cyclized via refluxing in DMF for 6 h to afford 18, while the transformation of compound 16 with an alkyl halide afforded 19a, b. The synthesized compounds, explicated by spectral data and elemental analysis, were examined for their antitumor activities. The in vitro cytotoxic activity of new pyrazolo[3,4-b]pyridines against the A2780CP, MCF-7, and HepG-2 cell lines was evaluated using the reference doxorubicin. Compounds 15 and 19a exhibited high reactivity against the A2780CP cell lines, with IC values of 35 and 17.9 μM, respectively. Also, compound 28 had the cytotoxic potential for A2780CP and MCF-7 cell lines, with IC values of 14.5, and 27.8 μM, respectively.
Topics: Humans; Molecular Structure; Drug Screening Assays, Antitumor; Antineoplastic Agents; Pyridines; MCF-7 Cells; Structure-Activity Relationship; Cell Proliferation; Cell Line, Tumor
PubMed: 37212385
DOI: 10.1002/cbdv.202300156 -
Applied and Environmental Microbiology Jul 2020Pyridine and its derivatives constitute the majority of heterocyclic aromatic compounds that occur largely as a result of human activities and contribute to...
Pyridine and its derivatives constitute the majority of heterocyclic aromatic compounds that occur largely as a result of human activities and contribute to environmental pollution. It is known that they can be degraded by various bacteria in the environment; however, the degradation of unsubstituted pyridine has not yet been completely resolved. In this study, we present data on the pyridine catabolic pathway in sp. strain 68b at the level of genes, enzymes, and metabolites. The gene cluster, responsible for the degradation of pyridine, was identified in a catabolic plasmid, p2MP. The pathway of pyridine metabolism consisted of four enzymatic steps and ended by the formation of succinic acid. The first step in the degradation of pyridine proceeds through a direct ring cleavage catalyzed by a two-component flavin-dependent monooxygenase system, encoded by (pyridine monooxygenase) and genes. The genes , , and were found to encode ()--(4-oxobut-1-enyl)formamide dehydrogenase, amidohydrolase, and succinate semialdehyde dehydrogenase, respectively. These enzymes participate in the subsequent steps of pyridine degradation. The metabolites of these enzymatic reactions were identified, and this allowed us to reconstruct the entire pyridine catabolism pathway in sp. 68b. The biodegradation pathway of pyridine, a notorious toxicant, is relatively unexplored, as no genetic data related to this process have ever been presented. In this paper, we describe the plasmid-borne gene cluster, which includes the complete set of genes responsible for the degradation of pyridine. A key enzyme, the monooxygenase PyrA, which is responsible for the first step of the catabolic pathway, performs an oxidative cleavage of the pyridine ring without typical activation steps such as reduction or hydroxylation of the heterocycle. This work provides new insights into the metabolism of -heterocyclic compounds in nature.
Topics: Arthrobacter; Biodegradation, Environmental; Genes, Bacterial; Multigene Family; Pyridines
PubMed: 32471913
DOI: 10.1128/AEM.00902-20 -
Angewandte Chemie (International Ed. in... Nov 2019(-)-Himeradine A is a complex lycopodium alkaloid with seven rings and ten stereogenic centers that shows anticancer activity against lymphoma L1210 cells. A total...
(-)-Himeradine A is a complex lycopodium alkaloid with seven rings and ten stereogenic centers that shows anticancer activity against lymphoma L1210 cells. A total synthesis has been developed that builds off prior work on (+)-fastigiatine. A 2,4,6-trisubstitited piperidine ring forms the core of the quinolizidine segment, and was prepared by diastereoselective reduction of a pyridine and classic resolution of an intermediate. The remaining secondary amine was introduced with a catalyst-controlled Overman rearrangement. The piperidine segment was coupled in a B-alkyl Suzuki reaction with a bicyclic bromoenone, which was a key intermediate for the synthesis of (+)-fastigiatine. The final transformation featured a transannular Mannich reaction and cyclization to complete the quinolizidine. Five bonds and four new rings were generated in this one-pot procedure. (-)-Himeradine A was prepared in 17 steps in the longest linear sequence.
Topics: Catalysis; Cyclization; Molecular Structure; Piperidines; Pyridines; Quinolizines; Stereoisomerism
PubMed: 31491044
DOI: 10.1002/anie.201910129 -
Spectrochimica Acta. Part A, Molecular... Feb 2022A series of coumarin-pyridine-based push-pull fluorophores were prepared starting from 1,2,4-triazines by using direct C-H functionalization...
A series of coumarin-pyridine-based push-pull fluorophores were prepared starting from 1,2,4-triazines by using direct C-H functionalization (S-reaction)-Diels-Alder-retro Diels-Alder domino reaction sequence. This efficient synthetic strategy allowed to obtain a series of 19 coumarin-pyridine fluorophores. Their photophysical properties were studied. While pyridine-substituted derivatives of 4-alkylcoumarins may be considered as alternative to coumarin dyes characterized by emission maxima mainly in a visible region with wavelengths of 402-415 nm, absorption in the UV range at 210-307 nm, and good photoluminescence quantum yields of 6-19%, all the derivatives of 4-phenylcoumarin did not exhibit any noticeable fluorescence. More detailed photophysical studies were carried out for two the most representative derivatives of 4-alkyl-coumarin-pyridines to demonstrate their positive solvatochromism, and the collected data were analyzed by using Lippert-Mataga equation, as well as Kosower and Dimroth/Reichardt scales. The obtained results demonstrate that the combining two chromophore systems, such as 2,5-diarylpyridine and coumarin ones, is promising in terms of improving the photophysical properties of the new coumarin-pyridine hybrid compounds.
Topics: Coumarins; Fluorescence; Fluorescent Dyes; Pyridines
PubMed: 34749256
DOI: 10.1016/j.saa.2021.120499