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A visible‐light‐promoted site‐selective difluoroalkoxylation of imidazo[1,2‐a]pyridines has been achieved using N‐fluorobenzenesulfonimide (NFSI) as a fluorinating agent. This practical reaction has a wide range of substrate scope for both imidazo[1,2‐a]pyridines and alcohols to give 3,3‐difluoro‐2‐alkoxy‐2‐arylimidazo[1,2‐a]pyridines in 65–93% yields. The reaction proceeded at room temperature, showed high functional group tolerance, and was amenable to scale‐up. Based on mechanistic investigation, a radical pathway is proposed. [ABSTRACT FROM AUTHOR]

Imidazole moiety when fused with other heterocyclic system form numerous compounds with different types of pharmacological and biological activities. In this review, we discussed a comprehensive analysis of the synthetic methodologies and reaction mechanisms for imidazo‐fused heterocyclic molecules. These molecules represent a crucial class of compounds due to their significant applications and versatile chemical reactivity. This article meticulously examined various synthetic routes for the construction of imidazo‐fused heterocycles, ranging from traditional methods to modern approaches such as microwave‐assisted reactions, NPs‐catalyzed reactions, light‐mediated synthesis, electrochemical reactions, and transition metal‐free synthesis routes. By consolidating the current knowledge and highlighting future directions, this review aims to serve as a treasure for research community in the fields of organic chemistry, medicinal chemistry, and material science. [ABSTRACT FROM AUTHOR]

Different classes of Imidazopyridine i.e., Imidazo[1,2-a]pyridine, Imidazo[1,5-a] pyridine, Imidazo[4,5-b]pyridine, have shown versatile applications in various fields. In this review, we have concisely presented the usefulness of the fluorescent property of imidazopyridine in different fields such as imaging tools, optoelectronics, metal ion detection, etc. Fluorescence mechanisms such as excited state intramolecular proton transfer, photoinduced electron transfer, fluorescence resonance energy transfer, intramolecular charge transfer, etc. are incorporated in the designed fluorophore to make it for fluorescent applications. It has been widely employed for metal ion detection, where selective metal ion detection is possible with triazole-attached imidazopyridine, β-carboline imidazopyridine hybrid, quinoline conjugated imidazopyridine, and many more. Also, other popular applications involve organic light emitting diodes and cell imaging. This review shed a light on recent development in this area especially focusing on the optical properties of the molecules with their usage which would be helpful in designing application-based new imidazopyridine derivatives. [ABSTRACT FROM AUTHOR]

ABSTRACT Here, we have succeeded in developing an eco‐efficient, mild, and metal‐free synthetic protocol for biologically significant scaffolds: imidazopyridines and their derivatives via radical cyclization from a wide variety of simple 2‐aminopyridines and phenacyl bromides as reactants and utilizing visible light as a reaction promoter in the ethanol/water solvent. To the best of our knowledge, the present strategy is the first example of visible light promoted synthesis of imidazo[1,2‐a]pyridine via the formation of C‐N bonds. The proposed methodology has various advantages namely quick reaction time, low cost, simple setup, high atom efficiency, easy‐availability of reactants and non‐involvement of specific glasswares and photo reactor system. [ABSTRACT FROM AUTHOR]

We have synthesized imidazopyridine-type ionic liquids and evaluated their properties. [Cnimpy][Br] (n = 4, 6, 8, 10), in which an alkyl group was introduced at the N1 position of imidazo[1,2-a]pyridine, were all solid at room temperature. Exchange of the counteranions of [Cnimpy][Br] with N(CN)2− and FSI− gave the ionic liquids [Cnimpy][N(CN)2] and [Cnimpy][FSI] in the liquid state at room temperature. In particular, the DSC thermogram of [C10impy][FSI] showed a clear melting point at 22 °C. In [Cnimpy][TFSI], ionic liquids consisting of cations with short alkyl chain lengths (n = 4,6) were solids at room temperature, while those with long alkyl chain lengths (n = 8,10) were liquids. [Cnimpy][FSI] has lower viscosity than other anion-consisting ionic liquids which showed a liquid state at room temperature. [Cnimpy][FSI] has lower viscosity than other anion-containing ionic liquids. In particular, [C4impy][FSI], with its relatively short alkyl chain length, exhibited a viscosity of 101 mPa·s at 25 °C, which renders it suitable for practical applications. [C4impy] [FSI] (50 μM acetonitrile solution) showed fluorescence with maximum absorption at 336 nm. Its fluorescence wavelength was shorter than that of imidazo[1,2-a]pyridine, whereas its fluorescence quantum yield (ΦF 0.39) was higher. Therefore, it is expected to be used as a composite material by employing FRET with a substance that exhibits fluorescence in the visible region.

Pharmacotherapy protocols used in cancer treatment are far from curative for many patients due to reasons such as drug-related toxicity and decreased effectiveness of the drug. Multidrug resistance is a defense mechanism developed by the cancer cell against different drug groups or drug combinations. One of the most important reasons is the increase in the efficiency or number of ABC transporters that ensure drug removal from the cell. Imidazopyridines, which are incorporated into the structure of many biomolecules, have been produced under laboratory conditions for many years. Imidazopyridines are effective anticancer agents that can kill cancer cells in various ways. In this review, we presented a detailed summary of studies in which imidazopyridines were used to overcome multidrug resistance by targeting ABC transporters in cancer cells. For this purpose, we collectively evaluated the synthesis strategies and laboratory results of the agents synthesized and used as drugs and the compounds whose clinical trials have not yet started. The introduction of several imidazopyridine derivatives as prescription drugs reflects the potential of these molecules. We think that agents that can provide targeted therapy will be used more frequently in the clinic and will improve treatment success. [ABSTRACT FROM AUTHOR]

In recent years, there has been increasing attention focused on various products belonging to the imidazopyridine family; this class of heterocyclic compounds shows unique chemical structure, versatile optical properties, and diverse biological attributes. The broad family of imidazopyridines encompasses different heterocycles, each with its own specific properties and distinct characteristics, making all of them promising for various application fields. In general, this useful category of aromatic heterocycles holds significant promise across various research domains, spanning from material science to pharmaceuticals. The various cores belonging to the imidazopyridine family exhibit unique properties, such as serving as emitters in imaging, ligands for transition metals, showing reversible electrochemical properties, and demonstrating biological activity. Recently, numerous noteworthy advancements have emerged in different technological fields, including optoelectronic devices, sensors, energy conversion, medical applications, and shining emitters for imaging and microscopy. This review intends to provide a state-of-the-art overview of this framework from 1955 to the present day, unveiling different aspects of various applications. This extensive literature survey may guide chemists and researchers in the quest for novel imidazopyridine compounds with enhanced properties and efficiency in different uses. [ABSTRACT FROM AUTHOR]

Novel imidazopyridines hydrazine conjugates were designed and synthesized for their anti‐tubercular (anti‐TB) activity. A cytotoxicity assay was conducted with Vero cells to determine the safety profile of the most effective compounds. It was found that compound (IA3) (MIC=0.78 μM) and (IA8) (MIC=1.12 μM) were nearly 3.7 and 2.5 times more active than pyrazinamide. Based on Density functional theory (DFT), these molecules exhibited better charge transfer between molecular orbital's, which made them suitable for biological applications. Molecular docking on Mycobacterium tuberculosis InhA bound to NITD‐916 (PDB: 4R9S) revealed that compounds possessed greater binding affinity towards proteins. In addition, the most active anti‐TB compounds (IA3) and (IA8) exhibited high levels of interaction with the target protein and exceptional safety profile, suggesting they may prove to be effective leads for new drugs. [ABSTRACT FROM AUTHOR]

A catalyst-, oxidant-free and green synthetic route for direct access to a series of novel imidazopyridine-linked coumarins has been devised through tandem C(sp2)–H functionalization/decarboxylation reaction in ethyl acetate as a sustainable medium. Moreover, the utilities of ensured products in further organic synthesis were conducted by Suzuki–Miyaura and Sonogashira cross-coupling reactions. The fluorescence characteristics of the produced molecules are appropriate, and the synthesized scaffolds could promisingly garner future attention in clinical diagnostics and bioimaging research. [ABSTRACT FROM AUTHOR]

In the current era, a potent drug is still needed on the market for the treatment of various diseases worldwide. Researchers mainly focus on those enzymes that cause these diseases. One of the major diseases is caused by an enzyme called urease, which increases the concentration of ammonia in the body upon hydrolysis. Researchers across the globe have keen interest to synthesize the potent inhibitor for this conversion. From this perspective, hybrid analogs of imidazopyridine and oxadiazole (1–20) were designed and efficiently synthesized followed by characterizing them through varied spectroscopic methods (1HNMR, 13CNMR, and HREI-MS). In addition, in vitro analyses of the synthesized compounds were conducted to evaluate their anti-urease potency. There was significant potential in most compounds analyzed, but analogs 15, 16, and 17 (IC50 = 2.20 ± 0.10 μM, IC50 = 2.50 ± 0.10 μM, and IC50 = 2.30 ± 2.10 μM, respectively) performed exceptionally well in comparison with thiourea (IC50 = 22.30 ± 0.44 μM). The selected candidates were further investigated under a molecular docking study to confirm protein ligand interactions. In addition, energy gap (E gap) of the HOMO–LUMO was explored via density functional theory studies.

Zn(II) coordination polymers are being increasingly studied for their stability and properties. Similarly, there is a growing interest in imidazo[1,5-a]pyridine derivatives, which show great potential in luminescence and pharmaceutical applications. In this work, we successfully synthesized and crystallized three new coordination polymers, using Zn(II) as the metallic node, dicarboxylic acids of different length and nature as linkers, and a linear ditopic imidazo[1,5-a]pyridine derivative, to explore the role of this molecule as a propagator of the dimensionality of the structure or as an ancillary ligand. Our work demonstrates the structural capability of imidazo[1,5-a]pyridines in an unexplored domain for this family of ligands. Notably, we observed a pronounced ability of this heterocyclic scaffold to establish π···π interactions in the solid state. The supramolecular π-stacked assemblies were theoretically analyzed using DFT calculations based on model structures. [ABSTRACT FROM AUTHOR]

Abstract Two series of novel imidazo[1,2-a]pyridine-2-carbohydrazide derivatives have been designed, synthesized, and evaluated for cytotoxic activity. Target compounds were designed in two series: aryl hydrazone derivatives that were devoid of triazole moiety (7a-e) and aryl triazole bearing group (11a-e). In vitro cytotoxicity screening was carried out using MTT assay against three human cancer cells including breast cancer (MCF-7), colon cancer (HT-29), and leukemia (K562) cell lines as well as a non-cancer cell line (Vero). Compound 7d bearing 4-bromophenyl pendant from aryl hydrazone series exhibited the highest cytotoxic potential with IC50 values of 22.6 µM and 13.4 µM against MCF-7 and HT-29 cells, respectively, while it was not toxic towards non-cancer cells up to the concentration of 100 µM. Cell cycle analysis revealed that 7d increased the number of MCF-7 cells in the G0/G1 phase and also induced apoptosis in these cells as revealed by Hoechst 33,258 staining. The molecular mechanism contributing to the anti-proliferative effect of the most potent compound was investigated in silico using Super Pred software and introduced PDGFRA as a plausible target for 7d. Molecular docking and molecular dynamic studies demonstrated Lys627 and Asp836 as key residues interacting with the active compound. Overall, 7d could serve as a suitable candidate for further modifications as a lead anticancer structure.

A metal‐free formylation of imidazopyridines by direct decarboxylative cross‐coupling of glyoxylic acid in presence of K2S2O8 as oxidant under mild and neutral conditions is described. This reaction features a broad substrate scope, good functional group tolerance, and generates products in good yields between 68–85 %. The translational capacity of the reaction from a laboratory methodology to gram‐scale synthesis has also been ensured. The involvement of a radical pathway has been demonstrated by radical trapping experiments with 2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPO) and 2,6‐di‐tert‐butyl‐4‐methylphenol (BHT). [ABSTRACT FROM AUTHOR]

A Selectfluor mediated regioselective π‐extended [3+1+1] annulation using imidazopyridines, acetophenones and DMF as carbon source has been realized. The current route compared to traditional π‐extended annulation reaction utilizes commercially available acetophenones as a cyclic partner and offers three C−C bond formations. This reaction displayed good functional group tolerance wherein DMF served as a carbon synthon. Five‐membered bridged chroman‐4‐one derivative of imidazopyridine has been achieved with 2‐hydroxy acetophenone, wherein DMF acted as a dual carbon synthon and offered four C−C and one C−O bond formation in one‐pot. [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]

In recent years, there has been increasing attention focused on various products belonging to the imidazopyridine family; this class of heterocyclic compounds shows unique chemical structure, versatile optical properties, and diverse biological attributes. The broad family of imidazopyridines encompasses different heterocycles, each with its own specific properties and distinct characteristics, making all of them promising for various application fields. In general, this useful category of aromatic heterocycles holds significant promise across various research domains, spanning from material science to pharmaceuticals. The various cores belonging to the imidazopyridine family exhibit unique properties, such as serving as emitters in imaging, ligands for transition metals, showing reversible electrochemical properties, and demonstrating biological activity. Recently, numerous noteworthy advancements have emerged in different technological fields, including optoelectronic devices, sensors, energy conversion, medical applications, and shining emitters for imaging and microscopy. This review intends to provide a state-of-the-art overview of this framework from 1955 to the present day, unveiling different aspects of various applications. This extensive literature survey may guide chemists and researchers in the quest for novel imidazopyridine compounds with enhanced properties and efficiency in different uses.

Alzheimer's dementia (AD), the most prevalent neurodegenerative disorder adversely affecting elderly citizens worldwide, is an incurable disorder with no effective medication found till date. Taking into account the seriousness of this issue, imidazopyridine-based benzothiazole-oxadiazole hybrid derivatives were synthesized as anti-Alzheimer's agents. The efficacy of these scaffolds was compared with the standard Donepezil (IC50 = 14.47 ± 1.20 μM for AChE and 19.90 ± 2.40 μM for BuChE). All the novel scaffolds exhibited biological activity covering a range of IC50 = 6.70 ± 1.65 μM and 41.65 ± 7.20 μM for AChE and 6.40 ± 1.80 μM for AChE and 44.65 ± 7.40 μM for BuChE. Analog 6p having IC50 = 6.70 ± 1.65 μM for AChE and 6.40 ± 1.80 μM for BuChE was found as the lead candidate of the series with maximum inhibition due to presence of small sized and highly electronegative fluoro moieties, inhibiting the enzymes through effective hydrogen bonds. These effective interactions were also studied in molecular docking investigations of the lead compounds. Furthermore, ADME analysis conducted in this study assisted the drug likeness of the potent analogs. Synthetic and structural confirmation of the hybrid derivatives was achieved through 13C NMR, 1H NMR and HREI-MS.

Keywords: imidazopyridine; cycloaddition; 2-aminopyridine; chromones; DTBP EN imidazopyridine cycloaddition 2-aminopyridine chromones DTBP 2570 2580 11 07/31/23 20230817 NES 230817 Graph Imidazopyridines are an important class of aza-fused heterocycles in the pharmaceutical industry, and they exhibit wide biological activities, Including, anticancer [1] and antibacterial [6] action, central nervous system modulation, [9] and kinase inhibition. HRMS (ESI+): I m i / I z i [M + H] SP + sp calcd for [C SB 14 sb H SB 10 sb BrN SB 2 sb O SB 2 sb ] SP + sp : 316.9920; found: 316.9923. For a proof of concept, we described a novel and facile I SB 2 sb /DTBP promoted synthesis of C3-carbonylated imidazopyridines from chromones and 2-aminopyridines via ring opening (3+2) cycloaddition by employing simple and readily available starting materials. [Extracted from the article]

A green electrochemical C(sp2)−H trifluoromethylation of imidazo[1,2‐a]pyridines by engaging Langlois' reagent is reported. This oxidative regioselective CF3‐functionalization strategy operates under open atmosphere, in an undivided cell and at ambient temperature. Regioselective C−CF3 bond formation was achieved exclusively by applying this mild protocol exhibiting broad functional group compatibility affording the desired product up to 79% isolated yield. Mechanistic studies indicated a radical pathway for this electrochemical redox transformation. [ABSTRACT FROM AUTHOR]

Purpose: Ulcer is a serious disease that is caused due to different bacteria and over usage of various NSAIDs which caused to reduce the defensive system of stomach. Therefore, some novel series are needed to overcome these issues. Methods: Oxazole-based imidazopyridine scaffolds (4a-p) were designed and synthesized by two step reaction protocol and then subjected to urease inhibition profile (in vitro). All the newly afforded analogs (4a-p) were found potent and demonstrated moderate to significant inhibition profile. Results: Particularly, the analogs 4i (IC50 = 5.68 ± 1.66 μM), 4o (IC50 = 7.11 ± 1.24 μM), 4 g (IC50 = 9.41 ± 1.19 μM) and 4 h (IC50 = 10.45 ± 2.57 μM) were identified to be more potent than standard thiourea drug (IC50 = 21.37 ± 1.76 μM). Additionally, the variety of spectroscopic tools such as 1H NMR, 13C NMR and HREI-MS analysis were employed to confirm the precise structures of all the newly afforded analogs. Discussion: The structure–activity relationship (SAR) studies showed that analogs possess the substitution either capable of furnishing strong HB like –OH or had strong EW nature such as -CF3 & –NO2 groups displayed superior inhibitory potentials than the standard thiourea drug. A good PLI (protein–ligand interaction) profile was shown by most active analogs when subjected to molecular study against corresponding target with key significant interactions such as pi-pi stacking, pi-pi T shaped and hydrogen bonding.

An electro-oxidative method for the ring opening of imidazopyridine derivatives is reported. This mild protocol offers a sustainable alternative to the existing harsh reaction conditions and unleashes an efficient approach to produce N -(pyridin-2-yl)amide derivatives with good tolerance of different functional groups. Systematic mechanistic studies provided insight into the reaction pathway and revealed that the residual water of DMSO is the source of oxygen atoms in the products. [ABSTRACT FROM AUTHOR]

Malaria continues to be a significant public health problem threatened by the emergence and spread of resistance to artemisinin‐based combination therapies and marked half a million deaths in 2016. A new imidazopyridine chemotype has been envisaged through scaffold‐hopping approach combined with docking studies for putative‐binding interactions with Plasmodium falciparum phosphatidylinositol‐4‐kinase (PfPI4K) target. The docking results steered to the synthesis of compound 1 [5‐(3‐(methylsulfonyl)phenyl)‐3‐(4‐(methylsulfonyl)phenyl)‐3H‐imidazo[4,5‐b]pyridine] followed by the in vitro screening for antiplasmodial activity and ADME‐PK studies. Combined with potent antimalarial activity of compound 1 (Pf3D7 IC50 = 29 nM) with meager in vitro intrinsic clearance, moderate plasma‐protein binding, and acceptable permeability, compound 1 displayed sustained exposure and high oral bioavailability in mice and can thus have the potential as next generation PI4K inhibitor for in vivo studies. [ABSTRACT FROM AUTHOR]

In breast cancer (BC), STAT3 is hyperactivated. This study explored the design of imidazopyridine-tethered pyrazolines as a de novo drug strategy for inhibiting STAT3 phosphorylation in human BC cells. This involved the synthesis and characterization of two series of compounds namely, 1-(3-(2,6-dimethylimidazo [1,2-a]pyridin-3-yl)-5-(3-nitrophenyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-(4-(substituted)piperazin-1-yl)ethanone and N-substituted-3-(2,6-dimethylimidazo[1,2-a]pyridin-3-yl)-5-(3-nitrophenyl)-4,5-dihydro-1H-pyrazoline-1-carbothioamides. Compound 3f with 2,3-dichlorophenyl substitution was recognized among the tested series as a lead structure that inhibited the viability of MCF-7 cells with an IC50 value of 9.2 μM. A dose- and time-dependent inhibition of STAT3 phosphorylation at Tyr705 and Ser727 was observed in MCF-7 and T47D cells when compound 3f was added in vitro. Calculations using density functional theory showed that the title compounds HOMOs and LUMOs are situated on imidazopyridine-pyrazoline and nitrophenyl rings, respectively. Hence, compound 3f effectively inhibited STAT3 phosphorylation in MCF-7 and T47D cells, indicating that these structures may be an alternative synthon to target STAT3 signaling in BC. [ABSTRACT FROM AUTHOR]

[Display omitted] • Discovery of first-in-class ZnII metal complexes as potent inhibitors of Zika viral infection. • Dual entry and replication inhibition Mode of Action. • High potency and selectivity in Vero cells. In this study, we synthesized and characterized a series of coumarin-imidazopyridine hybrid ligands (HL1 - HL4) and their corresponding Zn(II) complexes (C1 - C4). The ligands were synthesized via a two-step process in 56–90 % yields. The resulting ligands, were utilized to form Zn(II) complexes, characterized by conductivity measurements, HRMS, IR, 1H NMR spectroscopy and X-ray diffractions. Biological evaluations revealed that these compounds exhibited potent antiviral activity against Zika virus (ZIKV), with EC 50 values ranging from 0.55 to 4.8 µM and SI of up to 1490. Notably, the complexes (the first-in-class Zn(II) anti-ZIKV complexes) generally displayed enhanced activity compared to their respective ligands, with some compounds outperforming the reference antiviral, ribavirin. The Time of Addition assay suggested that while some compounds interfere with both viral entry (with a virucidal component) and replication phases, other only acted in replication phases. These results together with molecular modeling studies on ZIKV Envelope protein and ZIKV NS2B-NS3 offered insights for their mode of actions and further optimizations. [ABSTRACT FROM AUTHOR]

Zn(II) coordination polymers are being increasingly studied for their stability and properties. Similarly, there is a growing interest in imidazo[1,5-a]pyridine derivatives, which show great potential in luminescence and pharmaceutical applications. In this work, we successfully synthesized and crystallized three new coordination polymers, using Zn(II) as the metallic node, dicarboxylic acids of different length and nature as linkers, and a linear ditopic imidazo[1,5-a]pyridine derivative, to explore the role of this molecule as a propagator of the dimensionality of the structure or as an ancillary ligand. Our work demonstrates the structural capability of imidazo[1,5-a]pyridines in an unexplored domain for this family of ligands. Notably, we observed a pronounced ability of this heterocyclic scaffold to establish π···π interactions in the solid state. The supramolecular π-stacked assemblies were theoretically analyzed using DFT calculations based on model structures.

Fused pyridines are reported to display various pharmacological activities, such as antipyretic, analgesic, antiprotozoal, antibacterial, antitumor, antifungal, anti-inflammatory, and antiapoptotic. They are widely used in the field of medicinal chemistry. Imidazopyridines (IZPs) are crucial classes of fused heterocycles that are expansively reported on in the literature. Evidence suggests that IZPs, as fused scaffolds, possess more diverse profiles than individual imidazole and pyridine moieties. Bacterial infections and antibacterial resistance are ever-growing risks in the 21st century. Only one IZP, i.e., rifaximin, is available on the market as an antibiotic. In this review, the authors highlight strategies for preparing other IZPs. A particular focus is on the antibacterial profile and structure–activity relationship (SAR) of various synthesized IZP derivatives. This research provides a foundation for the tuning of available compounds to create novel, potent antibacterial agents with fewer side effects. [ABSTRACT FROM AUTHOR]

BACKGROUND: In our previous work, we applied a new synthetic strategy to design and synthesize a series of imidazopyridine mesoionic derivatives with an ester group. The newly synthesized compounds had excellent insecticidal activity against aphids; however, insecticidal activity against planthoppers was less than satisfactory. In the present study, we designed and synthesized a series of novel imidazopyridine mesoionic compounds, containing an amido group, and these compounds were found to have improved insecticidal activity against planthoppers. RESULTS: The bioassay results demonstrated that most of the target compounds had moderate‐to‐good insecticidal activity against Sogatella furcifera, and some exhibited good‐to‐excellent insecticidal activity against Aphis craccivora. Among them, compound C6 had the highest insecticidal activity against S. furcifera and A. craccivora, with LC50 values of 10.5 and 2.09 μg mL−1, respectively. Proteomic results suggested that the differentially expressed proteins mainly were enriched in the nervous system‐related pathways after compound C6 treatment. Enzymatic assay results showed that compound C6 and triflumezopyrim had a certain inhibitory effect on acetylcholinesterase. Molecular docking and real‐time quantitative PCR results indicated that compound C6 not only may act on the nicotinic acetylcholine receptor, but also may interact with the α4 and β1 subunits of this receptor. CONCLUSION: The results reported here contribute to the development of new mesoionic insecticides and further our understanding of the mode‐of‐action of imidazopyridine mesoionic derivatives. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB), an infectious remains a global health burden till date. Considering immense importance of theoretical tools in computer aided-drug designing, the current study focuses on common pharmacophore and QSAR analysis of 38 imidazopyridine analogues as anti-TB agents. Our developed atom-based, field-based, and multilinear regression based-QSAR models showed high values for statistical robustness for internal as well as external validations (a correlation coefficient: R2 > 0.9, least standard deviations, higher Fischer coefficient, and cross-validation correlation coefficient: Q2 > 0.5). From our ZINC-Drug-like analysis, we were retained with 5 hits (VS1-VS-5), among them VS-4 molecule was found to have high potency (predicted pIC50 (μM) value: 7.96 (against MTB H37Rv ATCC 27,294)) with good theoretical properties (high softness, and low hardness values). From our designed analogues (S1-S10), analogue S-10 was retained with high potency as well as good pharmacokinetics to act as good anti-mycobacterial agent in future. [ABSTRACT FROM AUTHOR]

Human African trypanosomiasis (HAT), a fatal infection caused by Trypanosoma brucei (T. brucei) is considered as a neglected disease in the tropical areas, and newer agents with unique mechanism of action are urgently needed. In this work, 65 Imidazopyridine analogues from known literature were selected for building statistically robust genetic algorithm (GA) based QSAR models. Furthermore, values for the various cross-validation properties supported its statistical robustness (model 1, R tr 2 = 0. 8 5 3 7 , RMSE cv = 0. 3 5 8 6 , MAE cv = 0. 2 6 4 2 , CCC cv = 0. 8 9 5 3 , and Q LMO 2 = 0. 7 8 8 7). Our in silico ADMET analysis revealed that a designed molecule, S10 may act as potent lead (T. brucei, pEC 5 0 (μ M), predicted = 8. 2 0 0) with better pharmacokinetics, no carcinogenicity, class III acute oral toxicity, minimal OCT1 and OCT2 inhibitions and no eye corrosion profiles. Our molecular docking analysis (on 42 drug targets) for a dataset and designed molecules demonstrated higher binding affinity of Imidazopyridine analogues with T. brucei farnesyl diphosphate synthase (TbFPPS) (PDB id: 2I19). This observation was further supported by 100 ns molecular dynamics analysis retaining better stability of complex. Thus, imidazopyridine analogues would provide a promising scaffold for the development of anti-HAT agents. Human African trypanosomiasis (HAT), a fatal infection caused by Trypanosoma brucei, is considered as a neglected disease in the tropical areas, and newer agents with unique mechanism of action are urgently needed. In this present work, 65 Imidazopyridine analogues from known literature were selected for building statistically robust genetic algorithm (GA) based QSAR models. Furthermore, values for the various cross-validation properties supported its statistical robustness. Our in-silico ADMET analysis revealed that a designed molecule, S10 may act as potent lead (T. brucei, pEC 50 (μM), predicted = 8.200) with better pharmacokinetics, no carcinogenicity, class III acute oral toxicity, minimal OCT1 and OCT2 inhibitions, and no eye corrosion profiles. [ABSTRACT FROM AUTHOR]

In the title molecule, C20H24Br2N4, the imidazopyridine moiety is not planar as indicated by the dihedral angle of 2.0 (2)° between the constituent rings; the 4-dimethylaminophenyl ring is inclined to the mean plane of the imidazole ring by 27.4 (1)°. In the crystal, two sets of C—H...π(ring) interactions form stacks of molecules extending parallel to the a-axis direction. Hirshfeld surface analysis indicates that the most important contributions to the crystal packing are from H...H (42.2%), H...C/C...H (23.1%) and H...Br/Br...H (22.3%) interactions. The optimized structure calculated using density functional theory (DFT) at the B3LYP/ 6–311 G(d,p) level is compared with the experimentally determined structure in the solid state. The calculated HOMO–LUMO energy gap is 2.3591 eV.

Most heteroaryl selenides and diselenides are biologically active, with some reported to act as antioxidants and show activities that are medicinally relevant; hence, the development of efficient methods for their synthesis is an important objective. Herein, a simple method for the synthesis of selenides and diselenides bearing imidazo[1,2-a]pyridine rings and their anticancer activity are described. The double C–H selenation of imidazo[1,2-a]pyridine with Se powder was catalyzed by CuI (10 mol %) ligated with 1,10-phenanthroline (10 mol %) at 130 °C under aerobic conditions. The selenides or diselenides were prepared almost selectively using selenium powder in an appropriate quantity under otherwise identical reaction conditions. The prepared selenides and diselenides bearing two imidazo[1,2-a]pyridine rings were all novel compounds. Among the prepared diselenides and selenides that exhibited cytotoxicity against cancer cells, bis[2-(4-methoxyphenyl)imidazo[1,2-a]pyridin-3-yl] diselenide showed an excellent anticancer activity and low cytotoxicity toward noncancer cells, suggesting that this diselenide is a potential lead compound for anticancer therapy.

Electrochemical synthesis offers a mild, simple, and efficient tool for the preparation of interesting and useful molecules, thus eluding severe chemical oxidizing and reducing agents used in conventional synthetic methods. In particular, electrochemical C-H activation is expected to play an important role in the direct functionalization of heterocyclic compounds. Over the past few decades, the research interest in imidazopyridine and indazole has increased significantly due to their multipurpose uses in medicinal and industrial chemistry. Therefore, structural modification of these heterocycles using electro-oxidation has become one of the important research topics among synthetic organic chemistry in recent time. This review provides a comprehensive discussion of electrochemical functionalization of indazoles and imidazopyridines published so far. A summary of the current challenges and the future direction for the development of efficient and green electrochemical methods for functionalization of these heterocycles is also presented. [ABSTRACT FROM AUTHOR]

In breast cancer (BC), STAT3 is hyperactivated. This study explored the design of imidazopyridine-tethered pyrazolines as a de novo drug strategy for inhibiting STAT3 phosphorylation in human BC cells. This involved the synthesis and characterization of two series of compounds namely, 1-(3-(2,6-dimethylimidazo [1,2-a]pyridin-3-yl)-5-(3-nitrophenyl)-4,5-dihydro-1H-pyrazol-1-yl)-2-(4-(substituted)piperazin-1-yl)ethanone and N-substituted-3-(2,6-dimethylimidazo[1,2-a]pyridin-3-yl)-5-(3-nitrophenyl)-4,5-dihydro-1H-pyrazoline-1-carbothioamides. Compound 3f with 2,3-dichlorophenyl substitution was recognized among the tested series as a lead structure that inhibited the viability of MCF-7 cells with an IC50 value of 9.2 μM. A dose- and time-dependent inhibition of STAT3 phosphorylation at Tyr705 and Ser727 was observed in MCF-7 and T47D cells when compound 3f was added in vitro. Calculations using density functional theory showed that the title compounds HOMOs and LUMOs are situated on imidazopyridine-pyrazoline and nitrophenyl rings, respectively. Hence, compound 3f effectively inhibited STAT3 phosphorylation in MCF-7 and T47D cells, indicating that these structures may be an alternative synthon to target STAT3 signaling in BC.

A one-pot electrochemical synthesis of two medically interesting compounds is presented. 2-Phenylimidazo[1,2-a]pyridine and 2-(4-fluorobenzylidene)malononitrile were prepared using previously used starting materials. The reaction consists of electrochemical methods without adding additional reagents, giving product yields of about 82–90% at 5.0 V, leading to a different approach for synthesizing important organic compounds with efficient route.

Fused pyridines are reported to display various pharmacological activities, such as antipyretic, analgesic, antiprotozoal, antibacterial, antitumor, antifungal, anti-inflammatory, and antiapoptotic. They are widely used in the field of medicinal chemistry. Imidazopyridines (IZPs) are crucial classes of fused heterocycles that are expansively reported on in the literature. Evidence suggests that IZPs, as fused scaffolds, possess more diverse profiles than individual imidazole and pyridine moieties. Bacterial infections and antibacterial resistance are ever-growing risks in the 21st century. Only one IZP, i.e., rifaximin, is available on the market as an antibiotic. In this review, the authors highlight strategies for preparing other IZPs. A particular focus is on the antibacterial profile and structure–activity relationship (SAR) of various synthesized IZP derivatives. This research provides a foundation for the tuning of available compounds to create novel, potent antibacterial agents with fewer side effects.

In the present work, the two imidazopyridine derivatives namely ethyl 6,8-dibromoimidazo [1,2-a] pyridine-2-carboxylate (ES-IMD) and (5-methylimidazo [1,2-a] pyridine-2-yl) methanol (OL-IMD) were presented as powerful anti-polarizing agent for steel surface in aggressive system related to the obtained results in experimental and computational methods. 1H NMR and mass spectrometry (MS) were used to confirm the structures of resynthesized molecule. We assessed the effectiveness of OL-IMD and ES-IMD inhibitors in safeguarding mild steel from corrosion in a 1 M hydrochloric acid environment. We adopted an integrated experimental and computational approach to evaluate the inhibition efficiency and mechanism of OL-IMD and ES-IMD, utilizing gravimetric method, polarization curves and electrochemical impedance spectroscopy. Quantum chemical calculations and molecular dynamics simulations provided atomic-level insights into adsorption behaviour. Scanning electron microscopy characterized surface morphology. Findings revealed that OL-IMD and ES-IMD compounds performed as mixed-type inhibitors. At the greatest inhibitor concentration (10−3 M), the polarization curves gave inhibition efficiency values of 98.91% (ES-IMD) and 95.42% (OL-IMD). Thermodynamic activation parameters indicated a spontaneous adsorption process of OL-IMD and ES-IMD on the steel surface, which effectively increased the energy barrier for the corrosion process. The EIS parameters demonstrated that when inhibitor concentration raised, the double-layer capacitance (C dl) dropped which suggested that the dielectric constant was decreasing. The results reveal a substantial correlation produced by the three analysed approaches EIS, PDP, and WL. Thermodynamic activation parameters indicated a spontaneous adsorption process of OL-IMD and ES-IMD on the steel surface, which effectively increased the energy barrier for the corrosion process. Furthermore, the calculated ΔG ads values for the considered compounds were -47.39 (kJ/mol) and 49.26 (kJ/mol) for OL-IMD and ES-IMD respectively, proving the chemical nature of the adsorption. Furthermore, SEM surface studies displayed a homogeneous surface while the tested inhibitors were present, but a damaged surface in the blank solution. The theoretical models closely aligned with the experimental data, presented an excellent overview of the investigated inhibitors' reactivity against mild steel confirming the validity of the findings. [ABSTRACT FROM AUTHOR]

The importance of transforming growth factor beta-activated kinase 1 (TAK1) to cell survival has been demonstrated in many studies. TAK1 regulates signalling cascades, the NF-κB pathway and the mitogen-activated protein kinase (MAPK) pathway. TAK1 inhibitors can induce the apoptosis of cancerous cells, and irreversible inhibitors such as (5Z)-7-oxozeaenol are highly potent. However, they can react non-specifically with cysteine residues in proteins, which may have serious adverse effects. Reversible covalent inhibitors have been suggested as alternatives. We synthesised imidazopyridine derivatives as novel TAK1 inhibitors, which have 2-cyanoacrylamide moiety that can form reversible covalent bonding. A derivative with 2-cyano-3-(6-methylpyridin-2-yl)acrylamide (13h) exhibited potent TAK1 inhibitory activity with an IC50 of 27 nM. It showed a reversible reaction with β-mercaptoethanol, which supports its potential as a reversible covalent inhibitor.

Objective: While chronic feeding with high-fat or high-sugar diets is known related to obesity and type 2 diabetes, later data have indicated that it is also related to depression and anxiety appearance. In this regard, multi-target drugs raise considerable interest as promising therapeutic solutions to complex diseases. Considering the pharmacological effects of the imidazopyridinederivative moiety imidazo[1,2-a]pyridine and the organoselenium molecules, the combination of both could be a feasible strategy to develop efficient drugs to handle obesity and related comorbidities, for example dyslipidemia and mood disorders. Methods The antidepressant-and anxiolytic-like properties of a selanylimidazopyridine compound, 2-Phenyl-3-(phenylselanyl)imidazo[1,2-a]pyridine (3-SePh-IP), were evaluated on high-fat/high-fructose diet (HFFD)-fed female Swiss mice. Key findings: Our results showed that a short-term HFFD (16 days) could promote a significant body weight gain, hypercholesterolemia, glucose intolerance, and anxiety- and depressive-like behaviour in mice. Concomitant treatment with 3-SePh-IP (10 mg/kg; i.p.) attenuated the HFFD-induced increase in cholesterol levels and blunted the anxiety- and depressive-like behaviour in mice. Conclusions: 3-SePh-IP holds multimodal pharmacological properties, which provide a rationale for further studies, for example to assess the underlying mechanisms linked to its anxiolytic- and antidepressive-like activities. [ABSTRACT FROM AUTHOR]

Two imidazopyridine derivatives 6-chloro-2-(4-chlorophenyl) imidazo [1,2-a]pyridine (IPCl1) and 6-chloro-2-(4-chlorophenyl)imidazo[1,2-a]pyridine-3-carbal-dehyde (IPCl2) were investigated as corrosion inhibitors of mild steel in 1.0M HCl medium using potentiodynamic polarization curves and electrochemical impedance spectroscopy. The concentrations used in this work ranged between 1.0 × 10–6 and 1.0 × 10–3 M. Those compounds were found to be good inhibitors. In addition, their adsorption on the mild steel surface obeyed the Langmuir adsorption isotherm. A quantum chemical calculation was computed using Gaussian 09 based on the density-functional theory method at B3LYP/6-31G (d, p) in order to relate some electronic properties of the studied compounds to the inhibition efficiencies achieved experimentally. The Fukui functions were calculated to estimate the most reactive sites of nucleophilic and electrophilic attacks. Finally, the molecular dynamics simulation was implemented to search for the equilibrium configurations of IPCl1 and IPCl2/Fe(110) adsorption systems in a hydrochloric acid solution at various temperatures. The theoretical and experimental results obtained were in good correlation. [ABSTRACT FROM AUTHOR]

The present paper discusses the adsorption and inhibitory effect of a new pyridine derivative, namely, 6-bromo-2-(4-methoxyphenyl)-3-nonyl-3H-imidazo[4,5-b] pyridine (PIP) on mild steel corrosion in molar hydrochloric acid medium. The experimental study was carried out using a series of techniques such as weight loss, potentiodynamic polarization and electrochemical impedance spectroscopy (EIS). The effectiveness of this compound reaches a maximum value of 92% at 10–4 M. The obtained results showed that the adsorption process on the metal surface follows the Flory–Huggins adsorption model. Scanning electron microscopy (SEM) confirmed the existence of an adsorption film on the MS. The relationship between the corrosion inhibition efficiency and the molecular electronic properties of the studied compound were performed using Quantum chemistry method at the level of DFT/B3LYP at 6-31G (d,p) basis set. Quantum chemical calculations indicated that the investigated molecule has a tendency to be protonated in the acid medium. Molecular dynamics (MD) simulations were performed to evaluate the reactivity (interactions) of the system Fe (110) surface/PIP in HCl. A very good agreement was recorded with the experimental data. [ABSTRACT FROM AUTHOR]

Abstract Herein, we present the first Suzuki–Miyaura cross-coupling in a sustainable natural deep eutectic solvent (NaDES) applied to biologically relevant imidazo-fused scaffolds imidazo[1,2-a]pyridine and imidazo[1,2-b]pyridazine. The choline chloride/glycerol (1:2, mol/mol) NaDES allowed the functionalisation of diverse positions on the heterocycles with various boronic acids, by using 2.5 mol% of readily available Pd(OAc)2. Notably, the catalytic system proceeds without any ligands or additives, without protection from the atmosphere.

The importance of transforming growth factor beta-activated kinase 1 (TAK1) to cell survival has been demonstrated in many studies. TAK1 regulates signalling cascades, the NF-κB pathway and the mitogen-activated protein kinase (MAPK) pathway. TAK1 inhibitors can induce the apoptosis of cancerous cells, and irreversible inhibitors such as (5Z)-7-oxozeaenol are highly potent. However, they can react non-specifically with cysteine residues in proteins, which may have serious adverse effects. Reversible covalent inhibitors have been suggested as alternatives. We synthesised imidazopyridine derivatives as novel TAK1 inhibitors, which have 2-cyanoacrylamide moiety that can form reversible covalent bonding. A derivative with 2-cyano-3-(6-methylpyridin-2-yl)acrylamide (13h) exhibited potent TAK1 inhibitory activity with an IC50 of 27 nM. It showed a reversible reaction with β-mercaptoethanol, which supports its potential as a reversible covalent inhibitor. [ABSTRACT FROM AUTHOR]

Synthesis of functionalized 2-pyridone derivatives from thiazolo[3,2-a]pyridine-6-carbohydrazides or tetrahydroimidazo[1,2-a]pyridine-6-carbohydrazides was developed using acetic acid as solvent at 70°C. Various carbohydrazides could be applied to this protocol, and the desired 2-pyridone products were isolated in excellent yields by simple filtration. This method has several additional advantages, such as simple operation, mild reaction conditions, simple work up, easy product isolation, and preparation of potentially bioactive compounds. [ABSTRACT FROM AUTHOR]

p‐tosylmethyl isocyanide (TosMIC) which is also known as van Leusen's reagent hold the three functionalized groups including the isocyanide and sulfonyl group and an alpha carbon which is acidic by nature. Tosyl set of this fortunate reagent acts as a good leaving group and assist the alpha carbon to contribute in a range of cyclization strategies. Exceptionally, TosMIC was also proved as a good sulfonylating and sulfomethylating reagent. TosMIC has proved as a powerful and versatile synthon and betrothed in the synthesis of broad range of heterocycles having pharmacological interest. This review is focused on synthetic utility of TosMIC in diverse range of heterocycles like five membered heterocycles, fused heterocycles, linked or tethered heterocycles, spiro compounds etc. It is also utilized for regio, chemo and stereoselective synthesis and production of sulfones and sulfinates. It serves as an important building block in various synthetic methodologies like multi component reaction, cyclization, domino, cascade and cycloaddition and metal catalysed reactions. Various new catalyst and novel methodologies were explored due to enormous use of this wonderful reagent. [ABSTRACT FROM AUTHOR]

The unregulated activation of STAT3 has been demonstrated to occur in many cancers and enhances tumour growth, migration, and invasion. Stimulation by cytokines, growth factors, and hormones triggers this activation by phosphorylating STAT3 at tyrosine 705. Novel imidazopyridine compounds were synthesized to evaluate the inhibition of STAT3 at Y705. Among the tested compounds, 16 reduced the level of phospho-STAT3, inhibited the downstream signalling cascade and subsequently attenuated the survival of hepatocellular carcinoma (HCC) cells. Further assays showed that the reduction effects of compound 16 on tyrosine 705 of STAT3 were attributed to up-regulation of protein tyrosine phosphatase SHP-1.

Two efficient thermally activated delayed fluorescent (TADF) emitters were developed by utilizing CN‐modified imidazopyridine as an acceptor unit. The CN‐modified imidazopyridine acceptor was combined with either an acridine donor or a phenoxazine donor through a phenyl linker to produce two TADF emitters, Ac‐CNImPy and PXZ‐CNImPy. The acridine‐based Ac‐CNImPy emitter exhibited sky‐blue emission with a CIE coordinate of (0.18, 0.38), whereas the phenoxazine‐donor‐based PXZ‐CNImPy showed greenish‐yellow emission with a CIE coordinate of (0.32, 0.58). A high photoluminescence quantum yield of 80 % was observed for the PXZ‐CNImPy emitter compared with 40 % for the Ac‐CNImPy emitter. Organic light‐emitting diodes based on the PXZ‐CNImPy emitter demonstrated high external quantum efficiency of 17.0 %. Hence, the CN‐modified imidazopyridine unit can be considered as a useful electron acceptor for the future design of highly efficient TADF emitters. [ABSTRACT FROM AUTHOR]

6-(2-Fluorophenyl)-N-(p-tolyl)imidazo[1,2-a]pyridine-2-carboxamide is an organic intermediate having both functions of azabicyclo and amide groups. In this paper, the title compound is obtained by the ring closure reaction, the Suzuki reaction, the hydrolysis and amidation reactions. The structure of the compound is confirmed by FT-IR, lH NMR, 13C NMR spectroscopy, and MS. At the same time, a single crystal of the title compound is measured by X-ray diffraction and subjected to crystallographic and conformational analyses. The molecular structure is further calculated using density functional theory (DFT) and compared with the X-ray diffraction value. The results of the conformation analysis indicate that the molecular structure optimized by DFT is consistent with the crystal structure determined by single crystal X-ray diffraction. In addition, the molecular electrostatic potential and frontier molecular orbitals of the title compound are further investigated using DFT, revealing some physicochemical properties of the compound. [ABSTRACT FROM AUTHOR]

Here in, we described the synthesis of novel bisheterocycles imidazopyridine bearing xanthenedione by reacting various substituted 2-phenylimidazo [1,2-a] pyridine-3-carbaldehyde with cyclohexane-1,3-dione in gluconic acid aqueous solution (GAAS) via a tandem Knoevenagel followed by Michael, cyclization & tautomerization sequence. The use of GAAS in organic synthesis offers significant benefits like cost-effective, simple operation, reusable catalyst and green method. The reaction completed in 2–12 h to afford white stable solid compounds with very good yield. The structures of the compounds are confirmed by analyzing MS, IR, 1H NMR and 13C NMR spectra. Further, the structure of compound 3 h was confirmed by XRD analysis. [ABSTRACT FROM AUTHOR]