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Critical Reviews in Analytical Chemistry 2024Pyridine derivatives are the most common and significant heterocyclic compounds, which play an important role in various fields ranging from medicinal to chemosensing... (Review)
Review
Pyridine derivatives are the most common and significant heterocyclic compounds, which play an important role in various fields ranging from medicinal to chemosensing applications. Pyridine derivatives possess different biological activities such as antifungal, antibacterial, antioxidant, antiglycation, analgesic, antiparkinsonian, anticonvulsant, anti-inflammatory, ulcerogenic, antiviral, and anticancer activity. Furthermore, these derivatives have a high affinity for various ions and neutral species and can be used as a highly effective chemosensor for the determination of different species. In this review article, generally used synthetic routes of pyridine, structural characterization, medicinal applications, and potential of pyridine derivatives in analytical chemistry as chemosensors have been discussed. We hope this study will support the new thoughts to design biological active compounds and highly selective and effective chemosensors for the detection of various species (anions, cations, and neutral species) in various samples (environmental, agricultural, and biological). [Figure: see text].
Topics: Pyridines; Humans; Animals
PubMed: 35724248
DOI: 10.1080/10408347.2022.2089839 -
Tuberculosis (Edinburgh, Scotland) Jul 2021Isoniazid (INH) remains a cornerstone for treatment of drug susceptible tuberculosis (TB), yet the quantitative structure-activity relationships for INH are not well...
Isoniazid (INH) remains a cornerstone for treatment of drug susceptible tuberculosis (TB), yet the quantitative structure-activity relationships for INH are not well documented in the literature. In this paper, we have evaluated a systematic series of INH analogs against contemporary Mycobacterium tuberculosis strains from different lineages and a few non-tuberculous mycobacteria (NTM). Deletion of the pyridyl nitrogen atom, isomerization of the pyridine nitrogen to other positions, replacement of the pyridine ring with isosteric heterocycles, and modification of the hydrazide moiety of INH abolishes antitubercular activity. Similarly, substitution of the pyridine ring at the 3-position is not tolerated while substitution at the 2-position is permitted with 2-methyl-INH 9 displaying antimycobacterial activity comparable to INH. To assess the specific activity of this series of INH analogs against mycobacteria, we assayed them against a panel of gram-positive and gram-negative bacteria, as well as a few fungi. As expected INH and its analogs display a narrow spectrum of activity and are inactive against all non-mycobacterial strains evaluated, except for 4, which has modest inhibitory activity against Cryptococcus neoformans. Our findings provide an updated analysis of the structure-activity relationship of INH that we hope will serve as useful resource for the community.
Topics: Antitubercular Agents; Gram-Negative Bacteria; Gram-Positive Bacteria; Isoniazid; Microbial Sensitivity Tests; Molecular Structure; Mycobacterium tuberculosis; Pyridines; Structure-Activity Relationship
PubMed: 34116482
DOI: 10.1016/j.tube.2021.102100 -
The Indian Journal of Tuberculosis Apr 2017Mycobacterium tuberculosis (MTB) infection has become an increasing health threat due to the worldwide emergence of multidrug-resistant MTB (MDR-MTB) strain. Isoniazid... (Review)
Review
Mycobacterium tuberculosis (MTB) infection has become an increasing health threat due to the worldwide emergence of multidrug-resistant MTB (MDR-MTB) strain. Isoniazid (pyridine) resistance problem is a complex process and is associated with mutations in several genes. However, the emergence of isoniazid (INH) resistant M. tuberculosis strains dictates the necessity for redesigning this old drug in order to create analogs effective against INH-resistant strains by using rational approach. In light of these findings, the present review discusses the synthesis, structural optimization, and modification in pyridine structure to combat the problem of multidrug-resistant tuberculosis.
Topics: Drug Resistance; Humans; Molecular Structure; Pyridines; Structure-Activity Relationship; Tuberculosis, Multidrug-Resistant
PubMed: 28410694
DOI: 10.1016/j.ijtb.2016.11.012 -
Future Medicinal Chemistry Feb 2020Over the last decades, few significant achievements have been made in tuberculosis (TB) therapy. As a result, there is an urgent need for new anti-TB drugs. Two new...
Over the last decades, few significant achievements have been made in tuberculosis (TB) therapy. As a result, there is an urgent need for new anti-TB drugs. Two new classes of -(imidazole/benzimidazole)-pyridine derivatives were designed, synthesized and evaluated for their antimycobacterial activity. The synthesis is efficient and straightforward, involving only two successive -alkylations. The anti-TB assay reveal that our compounds have an excellent anti-TB activity against both replicating and nonreplicating , are not cytotoxic, exhibited a very good intracellular activity and are active against drug-resistant strains, some compounds have a bactericidal mechanism. The absorption, distribution, metabolism, excretion and toxicity studies performed for one compound are promising, indicating that it is a good candidate for a future drug.
Topics: Anti-Bacterial Agents; Benzimidazoles; Humans; Imidazoles; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Pyridines; Tuberculosis
PubMed: 31916456
DOI: 10.4155/fmc-2019-0063 -
Chemistry (Weinheim An Der Bergstrasse,... Apr 2022Inclusion of a second nitrogen atom in the aromatic core of phosphorus-nitrogen (PN) heterocycles results in unexpected tautomerization to a nonaromatic form. This...
Inclusion of a second nitrogen atom in the aromatic core of phosphorus-nitrogen (PN) heterocycles results in unexpected tautomerization to a nonaromatic form. This tautomerization, initially observed in the solid state through X-ray crystallography, is also explained by computational analysis. We prepared an electron deficient analogue (2 e) with a fluorine on the pyridine ring and showed that the weakly basic pyridine resisted tautomerization, providing key insights to why the transformation occurs. To study the difference in solution vs. solid-state heterocycles, alkylated analogues that lock in the quinoidal tautomer were synthesized and their different H NMR and UV/Vis spectra studied. Ultimately, we determined that all heterocycles are the aromatic tautomer in solution and all but 2 e switch to the quinoidal tautomer in the solid state. Better understanding of this transformation and under what circumstances it occurs suggest future use in a switchable on/off hydrogen-bond-directed receptor that can be tuned for complementary hydrogen bonding.
Topics: Hydrogen Bonding; Nitrogen; Phosphorus; Pyridines
PubMed: 35213751
DOI: 10.1002/chem.202200472 -
ChemMedChem Apr 2022Obesity is a global epidemic associated with multiple severe diseases. Several pharmacotherapies have been investigated including the antagonists of melanin...
Obesity is a global epidemic associated with multiple severe diseases. Several pharmacotherapies have been investigated including the antagonists of melanin concentrating hormone receptor 1 (MCHR1). The design, synthesis, and biological studies of novel MCHR1 antagonists based on benzofuro-pyridine and pyrazino-indole scaffold was performed. We confirmed that fine-tuning lipophilicity and basic pK by modifying the benzyl group and introducing different substituents on the aliphatic nitrogen sidechain decreases both hERG inhibition and metabolic clearance. We have succeeded to develop excellent in vitro parameters in the case of compounds 17 (4-[(5-chloropyridin-2-yl)methoxy]-1-[4-(2-hydroxyethyl)-8-oxa-4-azatricyclo[7.4.0.0 , ]trideca-1(13),2(7),9,11-tetraen-11-yl]-1,2-dihydropyridin-2-one monohydrochloride) and 23 g (4-[(5-chloropyridin-2-yl)methoxy]-1-(1,2,3,4-tetrahydropyrazino[1,2-a]indol-8-yl)pyridin-2(1H)-one monohydrochloride), which can be considered as valuable tools for further pharmacological investigation.
Topics: Humans; Obesity; Pyridines; Receptors, Somatostatin; Structure-Activity Relationship
PubMed: 35041296
DOI: 10.1002/cmdc.202100707 -
Acta Parasitologica Mar 2023The imidazo[1,2-a] pyridines have huge applications in medicinal chemistry with potent activity against wide spectrum of infectious agents. The efficacy of...
BACKGROUND AND PURPOSE
The imidazo[1,2-a] pyridines have huge applications in medicinal chemistry with potent activity against wide spectrum of infectious agents. The efficacy of imidazo[1,2-a]pyridine on the in vitro growth of different piroplasms, including Babesia bovis, B. bigemina, B. divergens, B. caballi, and Theileria equi, was investigated in this study.
METHODS
The anti-piroplasm efficacy of imidazo[1,2-a] pyridines was assessed using a fluorescence-based SYBR Green I assay. Furthermore, efficacy of imidazo[1,2-a]pyridine against piroplasms following discontinuation of treatment was also assessed using a viability assay. In vitro cultures of B. bovis and T. equi were used to assess the imidazo[1,2-a]pyridine and diminazene aceturate (DA) interaction.
RESULTS
In vitro, imidazo[1,2-a]pyridine inhibited the growth of B. bovis, B. bigemina, B. caballi, and T. equi in a dose-dependent manner. The highest inhibitory effects of imidazo[1,2-a]pyridine were detected on the growth of B. caballi with IC value of 0.47 ± 0.07. Interestingly, the efficacy of imidazo[1,2-a]pyridine was higher against B. bigemina (IC: 1.37 ± 0.15) compared to the positive-control DA (IC: 2.29 ± 0.06). The viability test findings indicate that imidazo[1,2-a]pyridine had a long-lasting inhibitory effect on bovine Babesia parasites in vitro growth up to 4 days after treatment. Notably, when coupled with DA at 0.75 or 0.50 IC, a high concentration (0.75 IC) of imidazo[1,2-a]pyridine produced additive suppression of B. bovis growth which suggest that imidazo[1,2-a]pyridine/DA could be a promising combination therapy for the treatment of B. bovis.
CONCLUSION
The obtained encouraging findings pave the way for in vitro and in vivo efficacy trials of imidazo[1,2-a]pyridine derivatives against several piroplasmids.
Topics: Animals; Cattle; Babesia; Theileria; Pyridines; Babesiosis; Theileriasis
PubMed: 36637693
DOI: 10.1007/s11686-022-00655-w -
Organic Letters Jun 2023This study presents a DNA-compatible synthesis of diverse 5-arylimidazo[1,2-]pyridin-3-amine derivatives using the Suzuki-Miyaura reaction, followed by a...
This study presents a DNA-compatible synthesis of diverse 5-arylimidazo[1,2-]pyridin-3-amine derivatives using the Suzuki-Miyaura reaction, followed by a Groebke-Blackburn-Bienaymé (GBB) reaction. The GBB reaction demonstrates a wide substrate scope, mild one-pot reaction conditions, and compatibility with subsequent enzymatic ligation, highlighting its potential in DNA-encoded library technology.
Topics: Amines; Cyclization; DNA; Gene Library; Pyridines
PubMed: 37310879
DOI: 10.1021/acs.orglett.3c01366 -
Carbohydrate Research Apr 2017The stereoselective peracetylation of α-d-xylose (1) and α-l-arabinose (4) using a combination of triethylamine and acetic anhydride in the presence or absence of a...
The stereoselective peracetylation of α-d-xylose (1) and α-l-arabinose (4) using a combination of triethylamine and acetic anhydride in the presence or absence of a catalytic amount of dimethylaminopyridine (DMAP) is described. The peracetylated d-xylose and l-arabinose alpha pyranose anomers 2α and 5α are obtained in 97% and 56% yields respectively. The peracetylated d-xylose beta pyranose anomer 2β is obtained in 71% yield through simple modification of the reaction conditions. Details regarding synthesis and isolation optimization studies under different conditions are presented below. The stereoselective peracetylation reactions disclosed here have been used to separate mixtures of d-xylose and l-arabinose as their peracetylated derivatives 2β and 5α in 47% and 42% yields and can provide pure pentoses after deacetylation.
Topics: Acetylation; Catalysis; Polysaccharides; Pyridines; Stereoisomerism; Substrate Specificity; Sugars
PubMed: 28319681
DOI: 10.1016/j.carres.2017.03.008 -
Angewandte Chemie (International Ed. in... Jun 2018Signal amplification by reversible exchange (SABRE) turns typically weak magnetic resonance responses into strong signals making previously impractical measurements... (Review)
Review
Signal amplification by reversible exchange (SABRE) turns typically weak magnetic resonance responses into strong signals making previously impractical measurements possible. This technique has gained significant popularity because of its speed and simplicity. This Minireview tracks the development of SABRE from the initial hyperpolarization of pyridine in 2009 to the point in which 50 % H polarization levels have been achieved in a di-deuterio-nicotinate, a key step in the pathway to potential clinical use. Simple routes to highly efficient N hyperpolarization and the creation of hyperpolarized long-lived magnetic states are illustrated. To conclude, we describe how the recently reported SABRE-RELAY approach offers a route for parahydrogen to hyperpolarize a much wider array of molecular scaffolds, such as amides, alcohols, carboxylic acids, and phosphates, than was previously thought possible. We predict that collectively these developments ensure that SABRE will significantly impact on both chemical analysis and the diagnosis of disease in the future.
Topics: Alcohols; Amides; Carboxylic Acids; Catalysis; Humans; Hydrogen; Magnetic Resonance Spectroscopy; Niacin; Phosphates; Pyridines
PubMed: 29316071
DOI: 10.1002/anie.201710406