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Organic & Biomolecular Chemistry Aug 2014A series of phosphinimine ligands were designed and used in the Cu(i)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction of tetrazolo[1,5-a]pyridines and alkynes for...
A series of phosphinimine ligands were designed and used in the Cu(i)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction of tetrazolo[1,5-a]pyridines and alkynes for the first time. By optimizing the reaction conditions, an efficient catalytic system (CuCl/2-PyCH2N[double bond, length as m-dash]P(t)Bu3) was developed to give 1-(pyridin-2-yl)-1,2,3-triazole derivatives in moderate to excellent yields (46-98%).
Topics: Alkynes; Azides; Catalysis; Copper; Cycloaddition Reaction; Imines; Ligands; Molecular Conformation; Pyridines; Triazoles
PubMed: 24984611
DOI: 10.1039/c4ob01176g -
Molecules (Basel, Switzerland) Jul 2019In the present study, 4-methylpyridin-2-amine was reacted with 3-bromothiophene-2-carbaldehyde and the Schiff base...
In the present study, 4-methylpyridin-2-amine was reacted with 3-bromothiophene-2-carbaldehyde and the Schiff base (E)-1-(3-bromothiophen-2-yl)-N-(4-methylpyridin-2-yl)methanimine was obtained in a 79% yield. Coupling of the Schiff base with aryl/het-aryl boronic acids under Suzuki coupling reaction conditions, using Pd(PPh) as catalyst, yielded products with the hydrolysis of the imine linkages (--) in good to moderate yields. To gain mechanistic insight into the transition metal-catalyzed hydrolysis of the compounds, density functional theory (DFT) calculations were performed. The theoretical calculations strongly supported the experiment and provided an insight into the transition metal-catalyzed hydrolysis of imines.
Topics: Catalysis; Hydrolysis; Imines; Models, Molecular; Molecular Structure; Nitrogen; Palladium; Pyridines; Schiff Bases
PubMed: 31319634
DOI: 10.3390/molecules24142609 -
Bioorganic & Medicinal Chemistry Letters Apr 2013During the course of our study on the innovative ligand for nicotinic acetylcholinergic receptors, LNAChR, and in order to assess activity and toxicity profiles of the...
During the course of our study on the innovative ligand for nicotinic acetylcholinergic receptors, LNAChR, and in order to assess activity and toxicity profiles of the drug's metabolites, synthesis of the main metabolites was undertaken. This synthesis work was done in parallel by organic chemistry and by biotransformation of LNAChR. Filamentous fungus Aspergillus alliaceus (NRRL 315) neatly afforded three of the main metabolites, one of which arose from a very unexpected and very uncommon rearrangement.
Topics: Aniline Compounds; Aspergillus; Molecular Structure; Pyridines; Receptors, Nicotinic
PubMed: 23434224
DOI: 10.1016/j.bmcl.2013.01.086 -
Bioorganic Chemistry Jun 2021Liver cancer is the most common type of cancer in many countries. New studies and statistics show rising liver cancer worldwide, so it is essential to seek new agents...
Liver cancer is the most common type of cancer in many countries. New studies and statistics show rising liver cancer worldwide, so it is essential to seek new agents for this type of cancer. PIM1 has an attractive target in the discovery of cancer medications as it is very much expressed in a variety of malignancies and influences such as tumorigenesis, cell cycle progression, cellular proliferation, apoptosis, and cell migration. Accordingly, a series of pyridones and pyridine-amides were synthesized and tested for anti-liver cancer activity. In the synthetic strategy 4,6-diaryl-3-cyano-2-pyridones 3a-n were synthesized using one-pot four component synthetic method. Structural modifications were done on 4,6-diphenyl-3-cayno-2-pyridone 3a to enhance the activity. Alkylation in the presence of KCO afforded the O-alkylated products 4-6. The acetoxy hydrazide 7 was synthesized and cyclized into 1,3,4-oxadiazolethione 8 which alkylated on sulfur to give 10. Azide-coupling method was used to couple the 2-(pyridin-2-yloxy)acetohydrazide 7 to different amines and amino acid esters to furnish the products 12a-e and 13a-b. The synthesized derivatives were subjected to cytotoxic screening against HepG2 and THLE-2 cells, Compounds 10, 12e and 13a have a remarkable cytotoxic activity with IC values (10.7-13.9 µM). Compound 7 was found to be more cytotoxic by showing the lowest IC value of 7.26 compared to 5-FU (IC = 6.98 µM). It inhibited cell growth by 76.76%. Additionally, it significantly stimulated apoptotic liver cancer cell death with 49.78-fold (22.90% compared to 0.46% for the control) arresting cell cycle Pre-G1 with 35.16% of a cell population, compared to 1.57% for the control. Moreover, it validated the intrinsic apoptosis through upregulation of P53, and other related genes, with inhibition of anti-apoptotic genes through PIM-1 inhibition.
Topics: Antineoplastic Agents; Apoptosis; Cell Proliferation; Cells, Cultured; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Liver Neoplasms; Molecular Docking Simulation; Molecular Structure; Pyridines; Structure-Activity Relationship
PubMed: 33839579
DOI: 10.1016/j.bioorg.2021.104877 -
Nucleosides, Nucleotides & Nucleic Acids 2019An efficient, mild and rapid procedure was employed to prepare a novel series of pyridine glycosides. The protocol allows the reaction of 2-pyridone with...
An efficient, mild and rapid procedure was employed to prepare a novel series of pyridine glycosides. The protocol allows the reaction of 2-pyridone with 1,2,3,4,6-penta-O-acetyl-α-D-glucopyranose under solvent-free microwave-assisted synthesis using different solid supports. Silica gel has been found to be an efficient and environmentally friendly promoter. Structures of the new products were confirmed based on their elemental analyses and spectral data (LC-MS/MS, IR, UV, 1D- and 2D-NMR).
Topics: Glycosides; Microwaves; Molecular Structure; Pyridines
PubMed: 30663490
DOI: 10.1080/15257770.2018.1562075 -
The Journal of Physical Chemistry. A Jan 2005pi-pi Interaction in pyridine dimer and trimer has been investigated in different geometries and orientations at the ab initio (HF, MP2) and DFT (B3LYP) levels of theory...
pi-pi Interaction in pyridine dimer and trimer has been investigated in different geometries and orientations at the ab initio (HF, MP2) and DFT (B3LYP) levels of theory using various basis sets (6-31G, 6-31G, 6-311++G) and corrected for basis set superposition error (BSSE). While the HF and DFT calculations show the pyridine dimer and the trimer to be unstable with respect to the monomer, the MP2 calculations show them to be clearly stable, thus emphasizing the need to include electron correlation while determining stacking interaction in such systems. The calculated MP2/6-311++G binding energy (100% BSSE corrected) of the parallel-sandwich, antiparallel-sandwich, parallel-displaced, antiparallel-displaced, T-up and T-down geometries for pyridine dimer are 1.53, 3.05, 2.39, 3.97, 1.91, 1.47 kcal/mol, respectively. The results show the antiparallel-displaced geometry to be the most stable. The binding energies for the trimer in parallel-sandwich, antiparallel-sandwich, and antiparallel-displaced geometry are found to be 3.18, 6.14, and 8.04 kcal/mol, respectively.
Topics: Computer Simulation; Dimerization; Molecular Structure; Pyridines; Thermodynamics
PubMed: 16839083
DOI: 10.1021/jp045218c -
Bioorganic Chemistry Sep 2020Mycobacterium tuberculosis (MTB) infection has become a growing health risk as multi-drug resistant strain (MDR-MTB) has emerged worldwide. The development of isoniazid...
Mycobacterium tuberculosis (MTB) infection has become a growing health risk as multi-drug resistant strain (MDR-MTB) has emerged worldwide. The development of isoniazid (INH)-resistant M. tuberculosis strains dictate the need to re-design this old drug to create effective analogs against the resistant INH strains. Synthesis and the biological activity of isoniazid and pyridine derivatives were successfully carried out with elaborated characterization by spectral data. Amongst the synthesized compounds; 1 and 2 displayed encouraging antimycobacterial activity with IC of 3.2 µM and 1.5 µM against the H37Rv strain. The MIC of test compounds 1 and 2 were also assessed against the 5 drug resistant isolates (FQ-R1, INH-R1, INH-R2, RIF-R1 and RIF-R2) of MTB strains under aerobic conditions and compound 1 [MIC = 3.2 µM for FQ-R1; MIC = 140 µM for INH-R1; MIC = 160 µM for INH-R2; MIC = 2.4 µM towards RIF-R1; MIC = 4.2 µM for RIF-R2] and 2 [MIC = 3.3 µM for FQ-R1; MIC = 170 µM for INH-R1; MIC = 190 µM for INH-R2; MIC = 1.8 µM for RIF-R1; MIC = 8.4 µM for RIF-R2] have shown significant activity at non-cytotoxic concentration in comparison to the standard drug.
Topics: Antitubercular Agents; Dose-Response Relationship, Drug; Microbial Sensitivity Tests; Molecular Structure; Mycobacterium tuberculosis; Pyridines; Structure-Activity Relationship; Tuberculosis, Multidrug-Resistant
PubMed: 32711084
DOI: 10.1016/j.bioorg.2020.104099 -
European Journal of Medicinal Chemistry Apr 2019Alzheimer's disease (AD) is a neurodegenerative disorder with no radical therapy. Aggregation of amyloid β-peptide (Aβ) induced by various factors is associated with...
Alzheimer's disease (AD) is a neurodegenerative disorder with no radical therapy. Aggregation of amyloid β-peptide (Aβ) induced by various factors is associated with pathogenesis of AD. A pyridine amine derivative, 3-bis(pyridin-2-ylmethyl)aminomethyl-5-hydroxybenzyltriphenylphosphonium bromide (PAT), is synthesized. The inhibition of self- and metal-induced Aβ aggregation by PAT is confirmed by thioflavine T fluorescence, circular dichroism spectroscopy, and TEM. Western blot, RT-PCR and fluorescence imaging indicate that PAT can alleviate the Aβ-induced paralysis, reduce the production of ROS, and protect the mitochondrial function in transgenic C. elegans. Genetic analyses indicate that heat shock protein is involved in the alleviation of Aβ toxicity. PAT also inhibits the activity of acetylcholinesterase in C. elegans. Morris water maze test shows that the memory and cognitive ability of APP/PS1 AD model mice are significantly improved by PAT. Both in vitro and in vivo studies demonstrate that PAT is effective in counteracting Aβ toxicity and ameliorating cognitive functions in AD mice, and therefore a potential lead compound of anti-AD drugs.
Topics: Alzheimer Disease; Amines; Amyloid beta-Peptides; Animals; Caenorhabditis elegans; Dose-Response Relationship, Drug; Humans; Mice; Mice, Transgenic; Molecular Structure; Neuroprotective Agents; PC12 Cells; Protein Aggregates; Pyridines; Rats; Reactive Oxygen Species; Structure-Activity Relationship
PubMed: 30826509
DOI: 10.1016/j.ejmech.2019.02.052 -
Organic Letters Mar 2014The tetrasubstituted pyridinium amino acids isodesmosine and desmosine are cross-linkers of elastin and are attractive biomarkers for the diagnosis of chronic...
The tetrasubstituted pyridinium amino acids isodesmosine and desmosine are cross-linkers of elastin and are attractive biomarkers for the diagnosis of chronic obstructive pulmonary disease (COPD). In this study, the biomimetic total synthesis of isodesmosine and desmosine via a lanthanide-promoted Chichibabin pyridine synthesis using the corresponding aldehyde and amine hydrochloride is reported.
Topics: Biomarkers; Biomimetics; Cross-Linking Reagents; Desmosine; Elastin; Humans; Isodesmosine; Lanthanoid Series Elements; Molecular Structure; Pulmonary Disease, Chronic Obstructive; Pyridines; Pyridinium Compounds
PubMed: 24597689
DOI: 10.1021/ol500333t -
The Journal of Physical and Colloid... Mar 1949
Topics: Pyridines
PubMed: 18118434
DOI: 10.1021/j150468a009