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Alzheimer's disease (AD), a severe neurodegenerative disorder, imposes socioeconomic burdens and necessitates innovative therapeutic strategies. Current therapeutic interventions are limited and underscore the need for novel inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), enzymes implicated in the pathogenesis of AD. In this study, we report a novel synthetic strategy for the generation of 2-aminopyridine derivatives via a two-component reaction converging aryl vinamidinium salts with 1,1-enediamines (EDAMs) in a dimethyl sulfoxide (DMSO) solvent system, catalyzed by triethylamine (Et3N). The protocol introduces a rapid, efficient, and scalable synthetic pathway, achieving good to excellent yields while maintaining simplistic workup procedures. Seventeen derivatives were synthesized and subsequently screened for their inhibitory activity against AChE and BChE. The most potent derivative, 3m, exhibited an IC50 value of 34.81 ± 3.71 µM against AChE and 20.66 ± 1.01 µM against BChE compared to positive control donepezil with an IC50 value of 0.079 ± 0.05 µM against AChE and 10.6 ± 2.1 µM against BChE. Also, detailed kinetic studies were undertaken to elucidate their modes of enzymatic inhibition of the most potent compounds against both AChE and BChE. The promising compound was then subjected to molecular docking and dynamics simulations, revealing significant binding affinities and favorable interaction profiles against AChE and BChE. The in silico ADMET assessments further determined the drug-like properties of 3m, suggesting it as a promising candidate for further pre-clinical development. [ABSTRACT FROM AUTHOR]

Several heterocyclic compounds bearing an imidazo(1,2a)pyridine moiety have been synthesized in this work, including triazole, thiazol, and thiazolone. This was done by condensation of 2-aminopyridine with 2-aminopyridine with 4- bromophencyl bromide or 4-phenylphencyl bromide to produce 2-substituted phenyl imidazo(1,2a)pyridine compounds 1 and 2. The Vilsmeier-Haak reaction was used to create the aldehyde group at position 3 of the 2-substituted phenyl imidazo(1,2a)pyridine ring (3 and 4). The reaction of compounds 3 and 4 with thiosemicarbazide afforded thiosemicarbazone derivatives 5 and 6 in 66 and 70% yields, respectively. These derivatives (5 and 6) were then subjected to three different cyclization reactions to obtain 1,3-thiazolone (7 and 8), 1,2,4-triazole (9 and 10), and 1,3-thiazole (11 and 12) derivatives. The FT-IR spectroscopy was used to confirm the structure of these derivatives, and the 1H NMR spectroscopy was used for some of them. A few of the produced compounds were examined for antimicrobial and antioxidant activities [ABSTRACT FROM AUTHOR]

The metal-catalyzed carbenoid-based N–H insertions of α-stabilized diazo compounds and relative precursors serve as robust strategies for the formation of C–N bonds. However, carbenoid-based N–H insertions with aminopyridines are usually challenging due to the undesired coordination effect between the pyridine and the metal. Moreover, the coupling of donor/donor diazo compounds with amines remains challenging due to the instability and unavailability of donor/donor diazo compounds. Considering all these existing challenges, herein, a metal-free strategy is reported to achieve N–H insertions via coupling donor/donor diazo precursors (N-tosylhydrazones) with a plethora of amines including aminopyridines, anilines, aliphatic amines, and other nucleophiles such as imidazoles, pyrroles, and indoles. Expediently, β-amino esters are also afforded by using this mild strategy. The utility of this protocol is further demonstrated by the gram-scale synthesis and modifications of pharmaceuticals. Therefore, it is very clear that this metal-free approach uniquely tolerates a wide range of nucleophiles and opens a straightforward synthetic route to synthesize diverse value-added amines. [ABSTRACT FROM AUTHOR]

Pyridines and quinolines substituted with sulfur‐containing functional groups are widely used as drugs, drug candidates, organic materials, N,S‐ligands and others. Traditional synthetic routes to produce these compounds are based on nucleophilic aromatic substitution reactions and transition metal‐catalyzed cross‐coupling reactions of (pseudo)halopyridines. While effective in many cases, both approaches are limited due to using forcing conditions and expensive, specifically designed catalytic systems. In the last decade, a number of innovative methods for the functionalization of the pyridine ring via the formation of a C−S bond have been developed. Most of these methods proceed through the direct or indirect C−H functionalization of unfunctionalized pyridines, thus avoiding the use of oftentimes not readily available halopyridines as the starting materials. Deoxygenative C−H functionalization of pyridine‐N‐oxides and deaminative transformation of aminopyridines have been also employed for the introduction of diverse organosulfur functionality into the pyridine ring. All these processes can be easily performed under mild conditions, typically affording value pyridines and quinolines in good to high yields. Usually being highly chemo‐ and regioselective, these methods allow the late‐stage functionalization of complex molecules including drugs and natural products. In this Review, we summarize the most recent synthetic methods for functionalization of pyridines and fused pyridines with sulfur‐containing functional groups reported mostly since 2018. For a better understanding of the processes, the mechanisms of the described reactions are briefly discussed. [ABSTRACT FROM AUTHOR]

Reusable catalysts are attractive alternatives to the metal-free catalysts accelerating the Groebke–Blackburn–Bienayme reaction for the efficient synthesis of imidazo[1,2-α]pyridines. Herein, we report the synthesis of a reusable defective borocarbonitride catalyst with Lewis acidic boron and Lewis basic nitrogen, which switches the nature of the catalyst from Lewis acid to a frustrated Lewis pair (FLP). Furthermore, FLPs catalyzed the Groebke–Blackburn–Bienayme-type one-pot multi-component (2-aminopyridine, aldehyde and trimethylsilyl cyanide) reaction to afford 3-aminoimidazo[1,2-α] pyridines. Moreover, FLPs were employed for the synthesis of fused heterocyclic compounds for the first time. The noteworthy features of this protocol are its short reaction time, wide functional group tolerance, good yields and catalyst recovery. [ABSTRACT FROM AUTHOR]

In order to reduce the investment of corrosion inhibitors, based on experimental and theoretical studies, the corrosion inhibition and mechanism of new imidazoline derivatives (SMIS) and 2‐aminopyridine (AMP) were investigated carefully. The best corrosion inhibition effect was at 0.7‐g/L SMIS and 0.3‐g/L AMP, the corrosion inhibition efficiency of weight loss, electrochemical impedance spectroscopy, and potentiodynamic polarization (Tafel) were 90.54%, 98.56% and 97.68%, respectively. Electrochemical research shows that SMIS&AMP belongs to cathodic corrosion inhibition. SMIS&AMP mainly increased the film resistance and charge transfer resistance in 1‐M HCl, thus playing a certain role in corrosion inhibition. X‐ray photoelectron spectroscopy and energy dispersive spectrometer proved that SMIS&AMP can be adsorbed on the surface of Q235, molecular dynamics showed that there was a certain synergy between SMIS and AMP. This study confirmed that SMIS and AMP have a good synergistic effect, improve the corrosion inhibition efficiency, reduce the synthesis cost of SMIS, and have a certain guiding significance for synergistic corrosion inhibition. [ABSTRACT FROM AUTHOR]

The Buchwald–Hartwig cross‐coupling reaction of 3‐bromo‐4‐indolylmaleimide with various anilines, aminopyridines and amides is described. A wide variety of 3‐amino‐4‐indolylmaleimides and 3‐amido‐4‐indolylmaleimides was prepared in good to excellent yields. We envisage that our protocol to access 3‐(amino/amido)‐4‐indolylmaleimides will find use towards constituting new potentially biologically active compounds. [ABSTRACT FROM AUTHOR]

Enantiomorphous crystals of achiral 2‐pyridone and 4‐aminopyridine served as sources of chirality, to induce the asymmetric autocatalysis of 5‐pyrimidyl alkanol during the asymmetric addition of diisopropylzinc to the corresponding pyrimidine‐5‐carbaldehyde, that is, the Soai reaction. Following a significant amplification of enantiomeric excess through asymmetric autocatalysis, highly enantioenriched 5‐pyrimidyl alkanol could be synthesized with their corresponding absolute configurations to those of chiral crystals of 2‐pyridone and 4‐aminopyridine. [ABSTRACT FROM AUTHOR]

The X-ray crystal structures of some aminopyridine derivatives as contained in CSD have been examined for structure optimization and quantum chemical analysis. The experimental data and quantum chemical analysis uncover intriguing findings. The research extensively explores optimized structural geometry, the frontier orbital energy gap, the distribution of atomic Mulliken charges, and the molecular electrostatic potential (MEP). The Hirshfeld surfaces and their 2D fingerprint plots confirm the existence of N-H... N, O-H...N, and N-H...O intermolecular interactions in the molecules. The void volume percentage, which has been calculated to determine the physical strength of each molecule, is generally consistent among all the identified molecules. The energy frameworks reveal that electrostatic energy emerges as the dominant factor in each structure. [ABSTRACT FROM AUTHOR]

The main aspects of the reactivity of 2-aminopyridine N-oxides and similar heterocyclic systems are discussed. Literature data are systematized based on the types of transformations considered with a focus on the major advantages and disadvantages of each synthetic method. The possibility to synthesize previously inaccessible functionally substituted and bicyclic pyridine derivatives based on selective transformations of 2-aminopyridine N-oxides is demonstrated. [ABSTRACT FROM AUTHOR]

We developed a sequential intramolecular ring‐closure‐opening‐closure pathway using a catalyst‐free and organo‐base catalyzed system for the synthesis of fused regioselective tricyclic furo[3,2‐c]chromen and bicyclic imidazo[1,2‐a]pyridine via a one‐pot three‐component reaction. The protocol involved a Knoevenagel and Michael adduct via intramolecular cyclization with 4‐hydroxycoumarin, aromatic glyoxal, and 2‐aminopyridine under heating and ambient conditions with very good yields. The merits of this methodology were studied, and new practical ways were developed to access furo[3,2‐c]chromen and imidazo[1,2‐a]pyridine moieties. [ABSTRACT FROM AUTHOR]

With the recent spread in monkeypox cases, continuous efforts are made to manage the disease efficiently. Pain at the site of monkeypox lesions and in areas of skin breakdown can be severe. The origin of pain is likely neuropathic. The Centers for Disease Control and Prevention (CDC) has issued general guidelines to control pain with non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, gabapentin, and topical agents such as corticosteroids and lidocaine. Guidelines circulated by the World Health Organization (WHO) suggest acetaminophen, tramadol, opioids, and/or topical lidocaine for symptomatic pain management. No first line agent with proven beneficial effect has been recommended in these patients. We present two patients' painful experiences with Monkeypox and suggest lessons learned. [ABSTRACT FROM AUTHOR]

Clinical treatment by FDA-approved ROS1/ALK inhibitor Crizotinib significantly improved the therapeutic outcomes. However, the emergence of drug resistance, especially driven by acquired mutations, have become an inevitable problem and worsened the clinical effects of Crizotinib. To combat drug resistance, some novel 2-aminopyridine derivatives were designed rationally based on molecular simulation, then synthesised and subjected to biological test. The preferred spiro derivative C01 exhibited remarkable activity against CD74-ROS1G2032R cell with an IC50 value of 42.3 nM, which was about 30-fold more potent than Crizotinib. Moreover, C01 also potently inhibited enzymatic activity against clinically Crizotinib-resistant ALKG1202R, harbouring a 10-fold potency superior to Crizotinib. Furthermore, molecular dynamic disclosed that introducing the spiro group could reduce the steric hindrance with bulky side chain (Arginine) in solvent region of ROS1G2032R, which explained the sensitivity of C01 to drug-resistant mutant. These results indicated a path forward for the generation of anti Crizotinib-resistant ROS1/ALK dual inhibitors. SAR of a series of 2-aminopyridine ROS1/ALK inhibitors was studied. The spiro derivatives exhibited remarkable dual ROS1/ALK activity. C01 potently inhibited Crizotinib-refractory ALKG1202R and ROS1G2032R mutants. Molecular simulations gave a probable explanation for the activity of C01. [ABSTRACT FROM AUTHOR]

In this research, synthesis of different imidazopyridine derivatives was performed using aryl glyoxals, thiobarbituric acid, and 2-aminopyridine in the presence of acetic acid in ethanol at 80 °C. Different aryl glyoxals can be used in this method. Finally, the desired products were separated by simple filtration in excellent yields. The salient features of this protocol are a simple operation, mild reaction conditions, simple work up, easy product isolation, and preparation of potentially bioactive compounds. [ABSTRACT FROM AUTHOR]

[Display omitted] In consideration of energy shortages and environmental pollution, there is a critical need to develop a photocatalyst with high catalytic performance for rapid hydrogen production and efficient pollutant degradation. We synthesized a photocatalytic composite catalyst with three-dimensional (3D) porous aminopyridine rings grafted on the edge of g-C 3 N 4 (APCN) using melamine, cyanuric acid and 4-aminopyridine as raw materials. The composite catalyst exhibited excellent photocatalytic performance for H 2 production (2.44 mmol g−1h−1) and RhB degradation (97.08%) under visible light. Subsequently, a possible enhanced mechanism of the catalyst was proposed on the basis of a series of characterization and photocatalytic experiments. The 3D porous structure not only enhanced the structural stability but also increased the surface area of the APCN catalysts, which generated more exposed active sites. Moreover, the aminopyridine ring embellishment was beneficial for achieving a narrowed bandgap and charge migration and separation, which decreased the occurrence of photogenerated carrier recombination. In summary, these two structural features showed a synergistic effect to enhance the photocatalytic performance of the APCN catalyst. Finally, an integrated feasible enhanced mechanism of photocatalytic activity was elucidated according to the results of active substance capture tests, showing that O 2 •− played an important role during RhB degradation. [ABSTRACT FROM AUTHOR]

A series of Mn(II), Fe(III), and Co(II), complexes with two ligands derived from 2-aminopyridine, 4-hydroxy-2-methyl-N-(2-pyridyl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide (L1) and 2-{[3-(trifluoromethyl)phenyl]-amino}-3-pyridinecarboxylic acid (L2), was prepared and characterized using elemental analysis, molar conductance, TG measurements, IR, UV-Vis, ESR, and magnetic measurements. The coordination mode of L1 and L2 ligands was evaluated and the different geometries around the metals were determined. A complementary computational study using density functional theory (DFT) calculations was carried out to optimize the structures of the metal complexes and to confirm the proposed geometries. Using the same theoretical method, the investigation of the frontier molecular orbitals (FMOs) was used to predict the stability/reactivity of the complexes. The study of the complexation in solution allowed the determination of the stability constants of the complexes confirming their stability in solution. The distribution of the species involving Co(II) over the whole pH-range was also studied. The electrochemical behavior of the ligands and their metal complexes was determined by cyclic voltammetry which revealed irreversible redox processes for all the compounds. The study of the biological activities of the synthesized compounds indicates that the metal complexes displayed enhanced antioxidant and antibacterial properties. Molecular docking results of the Co–L1 complex with bacterial DHPS confirmed that the metal-based compound could efficiently inhibit bacterial growth while the interactions with cyclooxygenase (COX-1 and COX-2) revealed that the compound could act as efficient anti-inflammatory drugs. [ABSTRACT FROM AUTHOR]

3-chloro-4-hydroxyphenylacetic acid (CHPAA) is a fungal metabolite. It is a small molecule that is useful in crystal engineering studies due to the functional groups present. Six amines were selected to form salts with CHPAA. Linear derivatives included diethylamine (DEA) and di-N-butylamine (DBM). The aromatic compounds chosen were 2-aminopyridine (A2MP), 2-amino-4-methylpyridine (A24MP), 2-amino-6-methylpyridine (A26MP) and 4-dimethylaminopyridine (DMAP). The salts were characterised using single-crystal X-ray diffraction, thermal analysis, FTIR spectroscopy and Hirshfeld surface analysis. For all the crystal structures, N-H···O and C-H···Cl contacts were present. O-H···O contacts were found in all the crystal structures except for ( C H P A A 2 −) 2 D E A + , which was also the only structure that displayed a Cl···Cl contact. Furthermore, C-H···O contacts were found in all the crystal structures except for (C H P A A −) (D B M +).   The thermal stability trend showed that the DBM salt was more stable than the DEA salt. For the aromatic co-formers, the thermal stability trend showed the following: C H P A A − (D M A P +)   >   (C H P A A −) (A 2 M P +) > 2 C H P A A − 2 A 26 M P + > (C H P A A −) (A 24 M P +) . [ABSTRACT FROM AUTHOR]

Due to the high level of biological activity and other different interesting applications, 3-aroylimidazo[1,2-a]pyridines have received considerable attention in modern synthetic organic chemistry. This review is devoted to the different strategies for the synthesis of 3-aroylimidazo[1,2-a]pyridines in recent years (2016–2022) using homogeneous or heterogeneous catalysts. The first part is devoted to methods that use 2-aminopyridine and chalcone as starting reagents, then in the second part another variant that uses 2-aminopyridine and 3-phenylpropiolaldehyde, and finally fewer common methods that use other different reagents. Thus, this review will be of interest to many researchers in the field of organic and medicinal chemistry. [ABSTRACT FROM AUTHOR]

While fluorescent organic materials have many potential as well as proven applications and so have attracted significant attention, pyridine–olefin conjugates remain a less studied subset of such systems. Herein, therefore, we report on the development of the straightforward syntheses of pyridin-1(2H)-ylacrylates and the outcomes of a study of the effects of substituents on their fluorescent properties. Such compounds were prepared using a simple, metal-free and three-component coupling reaction involving 2-aminopyridines, sulfonyl azides and propiolates. The fluorescent properties of the ensuing products are significantly affected by the positions of substituents on the cyclic framework, with those located in central positions having the greatest impact. Electron-withdrawing groups tend to induce blue shifts while electron-donating ones cause red shifts. This work highlights the capacity that the micro-modification of fluorescent materials provides for fine-tuning their properties such that they may be usefully applied to, for example, the study of luminescent materials. [ABSTRACT FROM AUTHOR]

We have developed a short and highly efficient microwave-enhanced protocol for the synthesis of new Schiff bases, (E)-N-[(2-arylimidazo[1,2-a]pyridine-3-yl)methylidene]pyridin-2-amines, by the condensa-tion of 2-arylimidazo[1,2-a]pyridine-3-carbaldehydes with 2-aminopyridine in polyethylene glycol-400 as a green reaction medium in the presence of a catalytic amount of acetic acid. The essential features of this protocol are enhanced reaction rate, more eco-friendly reaction conditions, high yields, and green aspects such as avoiding toxic catalysts and hazardous organic solvents and reuse of the reaction medium. [ABSTRACT FROM AUTHOR]

Compounds with γ‐lactone fragments, as well as derivatives of 2‐aminopyridines and 2‐aminopyridons, are biologically active, and some of them are used as drugs. The condensed combination of γ‐lactones with 2‐aminopyridones, such as the natural alkaloid cerpegin, has a wider spectrum of biological activities. Here we combined γ‐lactone and 2‐aminopyridine derivatives into one molecule via a single bond. A series of such compounds were synthesized in high yields through the transformations of unsaturated furan‐2(5H)‐ones. Interestingly, only two of the obtained compounds underwent intermolecular cyclization and led to new isoquinoline derivatives with skeletons similar to the "proton sponges". [ABSTRACT FROM AUTHOR]

An unsymmetrical 2-(diphenylphosphino) aminobenzothiazole (DPA) was used to synthesize a heterogeneous and recyclable palladium composite through co-doping C3N4. The resulting palladium composite (DPA-Pd@g-C3N4) was carefully characterized by scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, X-ray diffraction, N2 sorption isotherms, thermogravimetricanalysis and energy dispersive X-ray spectroscopy. In addition, the composite DPA-Pd@g-C3N4 was successfully applied to the synthesis of N-substituted aminopyridine derivatives from the reaction of 2-aminopyridine and benzyl alcohols through borrowing hydrogen strategy. The corresponding palladium heterogeneous catalyst was synthesized through Pd-doped with C3N4 and revealed high catalytic activity for the synthesis of N-substituted aminopyridine with good recovery performance. [ABSTRACT FROM AUTHOR]

The present work involved ultrasound-promoted KI-Oxone mediated oxidative C–N bond formation from a reaction of β-ketoester and 2-aminopyridines leading to novel functional imidazo[1,2-a]pridine-3-carboxylates (IPCs). The α-halogenation of β-ketoester has been easily carried out by in situ formed I+ OH− species from the KI-Oxone system. IR, NMR, and Mass spectra characterized all derivatives. The structure of the synthesized IPCs was confirmed by X-ray crystallographic analysis. A transition metal-free protocol, one-pot synthesis, non-toxic reagents, benign reaction conditions, high yield, short reaction time, and the synthesis of highly functional IPCs are the remarkable features of the present method. The synthesized IPCs show unusual anti-tubercular activity. [ABSTRACT FROM AUTHOR]

Silica-zinc chloride (SiO2-ZnCl2)-mediated method has been developed for the synthesis of 2-nitro-3-arylimidazo[1,2-a]pyridine derivatives from 2-aminopyridines and β-nitrostyrenes. This new methodology offers operational simplicity, mild conditions, easy workup process, and good to excellent yields of various 3-aryl-2-nitroimidazo[1,2-a]pyridines. [ABSTRACT FROM AUTHOR]

The reaction of (1-ethoxyethylidene)malononitrile with cyanoacetamide or cyanothioacetamide has yielded 6-amino-4-methyl-2-(thio)oxo-1,2-dihydropyridine-3,5-dicarbonitriles. The resulting pyridine derivatives enter into the aminomethylation reaction with an excess of formaldehyde and primary amines with the formation of previously unknown 8-methyl-6-oxo-3-R-1,3,4,6-tetrahydro-2H-pyrido[1,2-a][1,3,5]triazine-7,9-dicarbonitriles. Further treatment of 6-amino-4-methyl-2-thioxo-1,2-dihydropyridine-3,5-dicarbonitrile and its oxygen analog with excess of formaldehyde has led to the formation of 3,10-dimethyl-1,8-dithioxo-5,6,12,13-tetrahydro-1H,8H-dipyrido[1,2-a:1′,2′-e][1,3,5,7]tetrazocin-2,4,9,11-tetracarbonitrile and 6,6′-[methylenedi(imino)]bis(4-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarbonitrile), respectively. These compounds have shown a pronounced antidote effect against the herbicide 2,4-D (2,4-dichlorophenoxyacetic acid) in laboratory and field experiments on sunflower seedlings. Furthermore, 6-amino-4-methyl-2-oxo-1,2-dihydropyridine-3,5-dicarbonitrile has exhibited pronounced anticorrosion properties, acting as an adsorption-type corrosion inhibitor. The mechanism of the anticorrosion action has been investigated in detail using X-ray photoelectron spectroscopy. [ABSTRACT FROM AUTHOR]

Four novel proton transfer compounds (1-4) obtained between 2-aminopyridine (1), 2-amino-4- methylpyridine (2), 2-amino-5-methylpyridine (3), 2-amino-6-methylpyridine (4) and 2,4- dichloro-5-sulfamoylbenzoic acid (Hsba) and their Cu(II) complexes (6-10) have been synthesized. The structures of powdery salts (1-4) and complexes (6-10) have been suggested by spectral (1H-NMR, FT-IR and UV–Vis), elemental analysis, AAS, molar conductivity and magnetic susceptibility techniques of 6-10 have also been reported. The structures of metal complexes (6-10) were observed octahedral according to spectroscopic analysis results. Additionally, anti-microbial and anti-fungal activities of all compounds have been tested against Escherichia coli (ATCC 25922) (Gram negative), Enterococcus faecalis (ATCC 29212) (Gram positive), Staphylococcus aureus (ATCC 29213) (Gram positive), and Candida Albicans (ATCC 14053) (yeast), Candida parapisilosis (ATCC 22019) (yeast), and Candida krusei (ATCC 6258) (yeast). The results were comparisoned with the antibiotics, Fluconazole as anti-fungal agent and Cefepime, Levofloxacin, Vancomycin as anti-microbial agents. Activity against all compounds bacteria and yeasts was observed. Therefore, all compounds may be utilized for the synthesis of new anti-microbial and anti-fungal. Compounds with the best activity are 2 (15.60 µg/mL) for S. aureus, 2, 8 and 11 (31.25 µg/mL) for E. Faecalis, 2a5mp, 1, 2 and 9 (31.25 µg/mL) for E. Coli, Cu(OAc)2.2H2O, 1, 2 and 9 (31.25 µg/mL) for C. Parapsilosis, Hsba (15.60 µg/mL) for C. Albicans and Hsba and 8 (31.25 µg/mL) for C. Krusei. [ABSTRACT FROM AUTHOR]

[Cu2(μ‐2‐chlorobenzoato‐O,O')4Cl2].2(4‐DMAPH) (1) and [Zn2(μ‐2‐chlorobenzoato‐O,O')4(4‐DMAP)2] (2) (4‐DMAP=4‐Dimethylaminopyridine) were synthesized from CuCl2/Zn(NO)3)2. 6H2O, 2‐chlorobenzoic acid and 4‐dimethylaminopyridine in methanol under reflux. Compounds were comprehensively characterized by elemental analyses, conductance measurement, spectroscopic and X‐ray diffraction studies. Complexes crystallized in the monoclinic space group P21/n having dinuclear paddle‐wheel structure. DFT studies along with NCI plot, QTAIM analysis indicate presence of N−H⋯Cl, C−H⋯O, C−H⋯π interactions in 1 and CH3⋯π, π⋯π and C−H⋯Cl in 2. The charge distribution in the complexes was shown via MEP analysis. Complexes interact with CT‐DNA in moderately strong non‐intercalative mode of binding. Antimicrobial study against Shigella flexneri (B), Streptococcus pneumoniae (K), Klebsiella pneumoniae (P) and Shigella boydii (Q) shows appreciable activity of 1 whereas compound 2 is comparatively less active. In vitro cytotoxicity study against cell lines (L‐132) exhibits moderate activity by the complexes, but compound 2 shows significant cell inhibition activity against cell lines K‐562. The complexes are emissive in nature. [ABSTRACT FROM AUTHOR]

Urine is considered an outstanding biological fluid for biomarker discovery, reflecting both systemic and urogenital physiology. However, analyzing the N-glycome in urine in detail has been challenging due to the low abundance of glycans attached to glycoproteins compared to free oligosaccharides. Therefore, this study aims to thoroughly analyze urinary N-glycome using LC-MS/MS. The N-glycans were released using hydrazine and labeled with 2-aminopyridine (PA), followed by anion-exchange fractionation before LC-MS/MS analysis. A total of 109 N-glycans were identified and quantified, of which 58 were identified and quantified repeatedly in at least 80% of samples and accounted for approximately 85% of the total urinary glycome signal. Interestingly, a comparison between urine and serum N-glycome revealed that approximately 50% of the urinary glycome could originate from the kidney and urinary tract, where they were exclusively identified in urine, while the remaining 50% were common in both. Additionally, a correlation was found between age/sex and the relative abundances of urinary N-glycome, with more age-related changes observed in women than men. The results of this study provide a reference for human urine N-glycome profiling and structural annotations. [ABSTRACT FROM AUTHOR]

Three proton‐transfer salts of diphenylphosphinic acid (DPPA) with 2‐amino‐5‐(X)‐pyridine (AMPY, X = Cl, CN or CH3), namely, 2‐amino‐5‐chloropyridinium diphenylphosphinate, C5H6ClN2+·C12H10O2P− (1, X = Cl), 2‐amino‐5‐cyanopyridinium diphenylphosphinate, C6H6N3+·C12H10O2P− (2, X = CN), and 2‐amino‐5‐methylpyridinium diphenylphosphinate, C6H9N2+·C12H10O2P− (3, X = CH3), have been synthesized and characterized by FT–IR and 1H NMR spectroscopy, and X‐ray crystallography. The crystal structures of compounds 1–3 were determined in the space group P for 1 and 2, and C2/c for 3. All three compounds contain N—H...O hydrogen‐bonding interactions due to proton transfer from the O=P—OH group of DPPA as donor to the pyridine N atom of AMPY as acceptor. The proton transfer of compounds 1–3 was also verified by 1H NMR and FT–IR spectroscopy. The stoichiometry of all three proton‐transfer salts was determined to be 1:1 and the Benesi–Hildebrand equation was applied to determine the formation constant (KCT) and the molar extinction coefficient (ϵCT) in each case. Theoretical density functional theory (DFT) calculations were performed to investigate the optimized geometries, the molecular electrostatic potentials (MEP) and the highest occupied molecular orbitals (HOMO) and lowest unoccupied molecular orbitals (LUMO) of all three proton‐transfer salts. The results showed good agreement between the experimental data and the DFT computational analysis. [ABSTRACT FROM AUTHOR]

Two effective flame retardant additives hsalaminopyridine phosphaphenanthrene (HAD) and methoaminopyridine phosphaphenanthrene (MAD) were respectively prepared with DOPO, aminopyridine, salicylaldehyde and 3-Methoxysalicylaldehyde. Subsequently, HAD and MAD was added into epoxy resin (EP) respectively, and flame retardancy of EP/HAD and EP/MAD thermosets were dramatically enhanced. The result of cone calorimeter (CC) test revealed that both HAD and MAD showed perfect smoke suppression performance. In respect of transmittance and mechanical properties, there was a huge difference between HAD and MAD. The introduction of HAD dramatically harmed transmittance and mechanical properties of EP, while, EP/10%MAD was transparent and nearly possessed the same mechanical properties with pure EP. [ABSTRACT FROM AUTHOR]

A facile, green, synthetic protocol of several substituted N-(pyridin-2-yl)imidates from nitrostyrenes and 2-aminopyridines via the corresponding N-(pyridin-2-yl)iminonitriles as intermediates is reported. The reaction process involved the in situ formation of the corresponding α-iminontriles under heterogeneous Lewis acid catalysis in the presence of Al2O3. Subsequently, α-iminonitriles were selectively transformed into the desired N-(pyridin-2-yl)imidates under ambient conditions and in the presence of Cs2CO3 in alcoholic media. Under these conditions, 1,2- and 1,3-propanediols also led to the corresponding mono-substituted imidates at room temperature. The present synthetic protocol was also developed on one mmol scale, providing access to this important scaffold. A preliminary synthetic application of the present N-(pyridin-2-yl)imidates was carried out for their facile conversion into the N-heterocycles 2-(4-chlorophenyl)-4,5-dihydro-1H-imidazole and 2-(4-chlorophenyl)-1,4,5,6-tetrahydropyrimidine in the presence of the corresponding ethylenediamine and 1,3-diaminopropane. [ABSTRACT FROM AUTHOR]

A highly selective molecularly imprinted polymer (MIP) to 4-Aminopyridine (4-Ap) target was synthesized starting with azobenzene monomers, which cross-linked initiated by 2, 2′‐azobisisobutyronitrile with the ethylene glycol dimethacrylate. The obtained sorbent, comprised of light-thermosensitive functions, was characterized using FTIR and SEM. The product was finally employed for the 4-AP target in solid-phase extraction. The effect of optimal parameters in the process was studied. The adsorption and release processes for 4-Ap drug delivery were investigated under various conditions, including temperature and radiation wavelengths. This study suggests a facile determination method high selectivity to 4-Ap adsorption/release in a real sample. [ABSTRACT FROM AUTHOR]

A novel magnetically recoverable copper nanocatalyst was fabricated via the immobilization of a copper complex on the surface of silica-coated magnetic nanoparticles modified with a novel Schiff base ligand [Fe3O4@SiO2-bis(aminopyridine)-Cu]. FT-IR spectroscopy, SEM, TEM, EDX, VSM, XRD, XPS, TGA and AAS, ICP-OES techniques were applied to characterize the structure of the as-fabricated [Fe3O4@SiO2-bis(aminopyridine)-Cu(II)] nanocomposite. TEM and SEM analysis confirmed that the typical silica shell thickness was assessed to be around 20 nm. Catalytic studies revealed that the Fe3O4@SiO2-bis(aminopyridine)-Cu(II) nanocomposite is a highly efficient and green nanocatalyst for the synthesis of benzothiazoles and polyhydroquinolines. The [Fe3O4@SiO2-bis(aminopyridine)-Cu(II)] nanocatalyst could be easily recovered by a simple magnetic separation and recycled at least 6 times without deterioration in catalytic activity. [ABSTRACT FROM AUTHOR]

Background: Most patients with chronic plaque psoriasis receive topical treatment; however, available options lack a balance of efficacy with long-term safety and tolerability. Roflumilast cream 0.3% is a highly potent phosphodiesterase 4 (PDE4) inhibitor approved by the US FDA for treatment of psoriasis. Objective: The aim of this study was to define the pharmacokinetic (PK) profile of roflumilast delivered topically from a phase I maximal usage study and data from phase II and phase III studies. Methods: PK data for roflumilast and the active metabolite, roflumilast N-oxide, were determined from a phase I PK and safety maximal usage study of roflumilast cream 0.3% applied once daily for 14 days in patients with plaque psoriasis affecting body surface area (BSA) ≥20% (N = 26). Serial plasma samples were obtained on Days 1 and 15 to determine maximum plasma concentration (Cmax) and area under the concentration-time curve (AUC). Plasma concentrations were also assessed at Weeks 3, 4, and 5 for terminal half-life (t½). Concentrations of roflumilast and roflumilast N-oxide in skin were assessed at Day 28 for 14 patients with psoriasis in a phase I/IIa study of once-daily roflumilast cream 0.5% and 0.15% for 28 days. Systemic exposure (Ctrough and AUC) of roflumilast and roflumilast N-oxide in two phase III trials (DERMIS-1, n = 245; DERMIS-2, n = 250) of roflumilast cream 0.3% for 8 weeks was assessed at Weeks 4 and 8. Results: Bioavailability of roflumilast cream 0.3% after topical administration was 1.5%. Unlike after oral dosing, the plasma concentration-time curve was flat, with a peak-to-trough ratio of 1.2. Roflumilast N-oxide concentrations were eightfold higher than roflumilast concentrations. The t½ in adult patients was 4.0 days for roflumilast and 4.6 days for roflumilast N-oxide following the last dose administered. Steady state was reached by Day 15. Concentrations of roflumilast in skin were, on average, 126- and 61.8-fold higher than corresponding mean plasma Ctrough following administration of roflumilast cream 0.15% and 0.5% daily for 28 days. Roflumilast N-oxide was quantifiable in only one skin sample (N = 27). Following 8 weeks of treatment in DERMIS-1, mean plasma Ctrough of roflumilast was 1.78 ng/mL, and 9.86 ng/mL for roflumilast N-oxide. In DERMIS-2, mean plasma Ctrough was 1.72 ng/mL and 10.2 ng/mL, respectively. In the maximal usage study (mean BSA: 27.5%), eight patients (30.8%) experienced adverse events (AEs) and all were mild or moderate, with no reports of diarrhea, headache, insomnia, or application-site pain; no patients discontinued treatment due to an AE. Conclusion: Topical administration of roflumilast cream 0.3% results in concentrations in skin 126- and 61.8-fold higher relative to plasma, which are much higher than expected to be achievable with oral dosing. PDE4 inhibition in the skin is likely due to roflumilast as compared with its active metabolite, as there is no significant conversion to roflumilast N-oxide in the skin. Consistent with reservoir formation and retention of drug in the stratum corneum, roflumilast is slowly released from the skin (t½ 4 days) and peak-to-trough ratio is 1.2. ClinicalTrials.gov Identifiers: NCT04279119, NCT03392168, NCT04211363, NCT04211389. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma is a brain tumor that is among the deadliest of human cancers. The invasive spreading of the tumor cells allows subpopulations to escape chemo and radiation treatments and infiltrate other areas of the brain where they continue to grow and cause relapses. To achieve their high motility, glioblastoma cells appear to harness membrane signaling proteins including aquaporin water channels, glutamate receptors, and ion channels. Work here tested selected combinations of agents that selectively targeted sets of signaling proteins known to be enriched in glioblastomas and showed that blocking both glutamate receptor and aquaporin-1 channels is an attractive means for limiting tumor cell motility without causing cell toxicity that might negatively impact normal brain cell function. Using combinations of agents at threshold doses could enable focusing of the pharmacological effects on cancer cells specifically, minimizing off-target effects. Impairing the motility of glioblastoma multiforme (GBM) cells is a compelling goal for new approaches to manage this highly invasive and rapidly lethal human brain cancer. Work here characterized an array of pharmacological inhibitors of membrane ion and water channels, alone and in combination, as tools for restraining glioblastoma spread in human GBM cell lines U87-MG and U251-MG. Aquaporins, AMPA glutamate receptors, and ion channel classes (shown to be upregulated in human GBM at the transcript level and linked to mechanisms of motility in other cell types) were selected as pharmacological targets for analyses. Effective compounds reduced the transwell invasiveness of U87-MG and U251-MG glioblastoma cells by 20–80% as compared with controls, without cytotoxicity. The compounds and doses used were: AqB013 (14 μM); nifedipine (25 µM); amiloride (10 µM); apamin (10 µM); 4-aminopyridine (250 µM); and CNQX (6-cyano-7-nitroquinoxaline-2,3-dione; 30 µM). Invasiveness was quantified in vitro across transwell filter chambers layered with extracellular matrix. Co-application of each of the ion channel agents with the water channel inhibitor AqB013 augmented the inhibition of invasion (20 to 50% greater than either agent alone). The motility impairment achieved by co-application of pharmacological agents differed between the GBM proneural-like subtype U87-MG and classical-like subtype U251-MG, showing patterns consistent with relative levels of target channel expression (Human Protein Atlas database). In addition, two compounds, xanthurenic acid and caelestine C (from the Davis Open Access Natural Product-based Library, Griffith University QLD), were discovered to block invasion at micromolar doses in both GBM lines (IC50 values from 0.03 to 1 µM), without cytotoxicity, as measured by full mitochondrial activity under conditions matching those in transwell assays and by normal growth in spheroid assays. Mechanisms of action of these agents based on published work are likely to involve modulation of glutamatergic receptor signaling. Treating glioblastoma by the concurrent inhibition of multiple channel targets could be a powerful approach for slowing invasive cell spread without cytotoxic side effects, potentially enhancing the effectiveness of clinical interventions focused on eradicating primary tumors. [ABSTRACT FROM AUTHOR]

Herein we describe the self‐assembly of an achiral molecule into macroscopic helicity as well as the emergent chiral‐selective spin‐filtering effect. It was found that a benzene‐1,3,5‐tricarboxamide (BTA) motif with an aminopyridine group in each arm could coordinate with AgI and self‐assemble into nanospheres. Upon sonication, symmetry breaking occurred and the nanospheres transferred into helical nanofibers with strong CD signals. Although the sign of the CD signals appeared randomly, it could be controlled by using the as‐made chiral assemblies as a seed. Furthermore, it was found that the charge transport of the helical nanofibers was highly selective with a spin‐polarization transport of up to 45 %, although the chiral nanofibers are composed exclusively from achiral building blocks. This work demonstrates symmetry breaking under sonication and the chiral‐selective spin‐filtering effect. [ABSTRACT FROM AUTHOR]

Herein we describe the self‐assembly of an achiral molecule into macroscopic helicity as well as the emergent chiral‐selective spin‐filtering effect. It was found that a benzene‐1,3,5‐tricarboxamide (BTA) motif with an aminopyridine group in each arm could coordinate with AgI and self‐assemble into nanospheres. Upon sonication, symmetry breaking occurred and the nanospheres transferred into helical nanofibers with strong CD signals. Although the sign of the CD signals appeared randomly, it could be controlled by using the as‐made chiral assemblies as a seed. Furthermore, it was found that the charge transport of the helical nanofibers was highly selective with a spin‐polarization transport of up to 45 %, although the chiral nanofibers are composed exclusively from achiral building blocks. This work demonstrates symmetry breaking under sonication and the chiral‐selective spin‐filtering effect. [ABSTRACT FROM AUTHOR]

The new polynucleating tripodal proligand H6tren(dpa)3, containing thirteen nitrogen donors of four different types, was designed, synthesized, and isolated in good yield (~60%) via a transition-metal-free triple N-arylation of H6tren with HXdpa (X = Br or F), using K2CO3 or Cs2CO3 as a base (H6tren = tris(2-aminoethyl)amine, HXdpa = 6-halogeno-N-(pyridin-2-yl)pyridin-2-amine). HFdpa was prepared with excellent yield (90-92%) by reaction of 2,6-difluoropyridine with 2-aminopyridine in LiH/toluene/pyridine and was found more reactive than HBrdpa, affording higher conversion and higher yield. Use of Cs2CO3 turned out to be essential for achieving high regioselectivity and eliminating overarylation almost completely. [ABSTRACT FROM AUTHOR]

Reaction of 5-hydrazinyl-substituted 1,2,4-triazines and 2,5-norbornadiene at elevated pressure and temperature (in autoclave) has been studied; the reaction yields 2-aminopyridines, 5-amino-1,2,4,-triazines, and 6-unsubstituted pyridines (formation of one of two latter products is dependent on the nature of substituent in the C3 position of triazine). [ABSTRACT FROM AUTHOR]

Azabenzimidazoles are among the substrates most frequently found in small-molecule drugs due to their broad-spectrum biological activity. Newer drugs are continually in need of to replace existing drugs which encounter microorganism drug resistance. The reaction of 2,3-diaminopyridine precursors with variously substituted benzaldehydes has provided convenient and efficient access to a series of 4-azabenzimidazole derivatives and, regioselectively, to a series of 2-amino-5-bromo-3-(phenylimino)pyridine derivatives, while sodium cyanoborohydride reduction of the latter has afforded the corresponding 2-amino-5-bromo-3- (phenylamino)pyridine analogues. Bioassays of these and other compounds have been undertaken to explore their cytotoxicity and their activity against the parasitic protozoans, Plasmodium falciparum and Trypanosoma brucei. A number of the compounds show promising selective activity against T. brucei with IC50 values as low as 1.3 µM while two of them exhibit encouraging activity against both T. brucei and P. falciparum. [ABSTRACT FROM AUTHOR]

A silver‐promoted decarboxylative annulation of alkynoic acids with 2‐aminopyridines has been developed to assemble 2‐arylimidazo[1,2‐a]pyridines. Various functionalities in the aromatic rings in the two substrates are well tolerated in this reaction and gave the desired products in good yields for a broad scope of substrates. Additional advantages of this protocol include mild reaction conditions and high regioselectivity. This report represents the first example of synthesis of 2‐arylimidazo[1,2‐a]pyridines from alkynoic acids. [ABSTRACT FROM AUTHOR]

Increasing self-efficacy to exercise and minimizing disease-related barriers has been shown to improve physical activity levels and quality of life (QOL) in persons with multiple sclerosis (MS). Currently, little research has examined exercise self-efficacy in persons with more advanced MS. Purpose: Explore the effects of a self-efficacy plus exercise intervention on physical activity endurance and level, QOL, and fatigue in an individual with advanced MS and low self-efficacy. The participant was a 60-year-old, severely disabled female with secondary progressive MS and an Expanded Disability Status Score (EDSS) of 8. The 8-week intervention consisted of weekly discussions and MS-related education; four one-on-one sessions with a MS "mentor;" daily journal to record sleep quality, fatigue level, and physical activity. Outcomes included a modified 5-meter walk test (5MWT), MS Impact Scale (MSIS-29), Exercise Self-Efficacy Scale (EX-ES), Modified Fatigue Impact Scale (MFIS), MS Self-Efficacy Scale (MS-SES), Patient Health Questionnaire-9 (PHQ-9), and daily physical activity monitoring. Outcomes were assessed at baseline (week 0), post-intervention (week 8), and 8 weeks post intervention (week 16). The participant continued her regular exercise routine independently throughout the study period. There were notable improvements in EX-ES, MFIS, PHQ-9, MSIS-29 psychological subscale, sleep quality, and morning fatigue ratings post intervention, some of which were retained at follow up. The findings illustrate that an 8-week self-efficacy intervention increased exercise self-efficacy, QOL, and reduced perceived fatigue in a severely disabled individual with progressive MS. Future research should examine self-efficacy interventions in a larger sample size of persons with progressive MS. [ABSTRACT FROM AUTHOR]

The cocrystallization of the earlier described carboxy-containing iron(II) clathrochelate (I) with 2-hydroxypyridine and 2-aminopyridine affords two new crystalline products: the salt and cocrystal of this complex, respectively, formed by the acid–pyridine two-point heterosynthone, which is often met in multicomponent crystals of aromatic acids and ortho-substituted pyridines. The neutral nature of the cocrystallization product with 2-hydroxypyridine violates the rule of pKa, which is fulfilled in the case of 2-aminopyridine, because of the equilibrium shift in the crystalline phase toward the keto form of 2-hydroxypyridine: pyridone-2. According to the X-ray diffraction (XRD) data, complex I in the salt and cocrystal exists in the low-spin state and undergoes no temperature-induced transition in a temperature range of 100–298 K. [ABSTRACT FROM AUTHOR]

Herein, we report the first example of diazotization of aminopyridines and aminoquinolines with t-BuONO in hexafluoropropan-2-ol in the absence of acids or other initiators. For aminopyridines, this reaction is the first general route toward 2-, 3-, and 4-[(1,1,1,3,3,3-hexafluoropropan-2-yl)oxy]pyridines. [ABSTRACT FROM AUTHOR]

A method for the preparation of 2-morpholinocinchomeronic acid dinitrile derivatives (2-morpholinopyridine-3,4-dicarbonitriles) was developed. The optical properties of the obtained products were investigated both in solution and the solid state. It was found that the synthesized compounds exhibit fluorescence both in solution and in the solid state from the blue to green region of the spectrum, depending on the substituents at the fifth and sixth positions of the pyridine ring. It was found that the relative quantum yield in benzene reaches 50%. [ABSTRACT FROM AUTHOR]

One‐pot solvothermal reaction of 2‐aminopyridine and triethyl orthoformate with Ni(OAc)2 ⋅ 4H2O afforded a one dimensional (1D) nickel coordination polymer {[Ni(Dpyf′)] ⋅ MeOH}n (Dpyf′=C11H9N4−), 1, which has been structurally characterized by using single crystal X‐ray crystallography. Complex 1 can be considered as a potential heterogeneous catalyst for nitroaldol (Henry) reaction for C−C bond formation. [ABSTRACT FROM AUTHOR]

New representatives of 2-(butylamino)cinchomeronic dinitrile derivatives were synthesized as promising fluorophores showing dual-state emission. To characterize the influence of the length (from methyl to butyl) and the structure (both linear and branched) of the alkyl substituent at the amino nitrogen atom, the spectral fluorescence properties of all synthesized compounds were carefully studied both in solution and in solid state. The highest photoluminescence quantum yield values of 63% were noted for solutions of 2-(butylamino)-6-phenylpyridine-3,4-dicarbonitrile in DCM and 2-(butylamino)-5-methyl-6-phenylpyridine-3,4-dicarbonitrile in toluene. [ABSTRACT FROM AUTHOR]

The base-catalyzed hydroamination reaction of teramethyl ethynyldiphosphonate with substituted 2-aminopyridines was studied. The reaction proceeds stereoselectively with the formation of (E)-enaminophosphonates. A series of new phosphonoenamines, namely dimethyl [2-(dimethoxyphosphoryl)-2-(pyridin-2-ylamino)vinyl]phosphonates, was obtained. [ABSTRACT FROM AUTHOR]

A novel, versatile and efficient magnetically recoverable palladium nanocatalyst [Fe3O4@SiO2/2-aminopyridine-Pd(II)] was fabricated via the immobilization of palladium(II) complex on the surface of magnetic nanoparticles modified with 2-aminopyridine ligand. The structure of the as-fabricated Fe3O4@SiO2/2-aminopyridine-Pd(II) nanocomposite was characterized by a series of spectroscopic techniques including FT-IR, SEM, TEM, EDX, TGA, XRD, VSM and ICP-OES techniques. The Fe3O4@SiO2/2-aminopyridine-Pd(II) nanocomposite was utilized under mild and eco-friendly conditions in C–S and C–Se coupling reactions to afford a vast variety of diaryl sulfides and diaryl selenides with good to excellent yields. This heterogeneous palladium catalyst can be magnetically separated and reused for at least 7 consecutive trials without any reduction in activity. [ABSTRACT FROM AUTHOR]