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Tubulin and the tubulin cycle, which have many vital cellular functions in living cells, are privileged targets for the development of anticancer drug candidates. In the processing of cellular processes, especially cell division, alpha and beta tubulin polymerize to form microtubules and continue the cycle by depolymerizing again. Disruption of the polymerization-depolymerization dynamics of microtubules by various agents causes mitotic cell arrest and subsequent cell death via apoptosis. This review summarizes the tubulin cycle, cancer, and target regions. Tubulin has three main target binding sites: taxane, vinca, and colchicine. In particular, the colchicine binding site, which is the current target for disrupting the tubulin cycle, is inhibited by various synthetic compounds, and the common properties of these compounds are emphasized. The results show that highly effective cytotoxic agents can be developed by modifying the imidazopyridine scaffold, which remains open to exploration. The remarkable antitubulin and cytotoxic effects of recently developed compounds with an imidazopyridine ring are interesting. A detailed report of anti-tubulin agents with imidazopyridine structures, among the tubulin polymerization inhibitors developed to date, and an evaluation of the structure–activity relationship is presented here. In addition, the new molecular topology established in this review based on the structure-activity relationships of imidazopyridine will inspire research groups to develop new imidazopyridine-based anti-tubulin agents with clinical anticancer potential in the near future. [ABSTRACT FROM AUTHOR]

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]

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.

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]

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]

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]

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.

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]

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]

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 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]

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.

• New imidazopyridine analogues were designed for anti-TB activity. • I2 and I7 exhibited MIC of 3.12 and 4.16 μg/mL against MTBH 37 Rv strain. • I2 and I7 was found to be more active than standard drug streptomycin. • Molecular docking data were in accordance with the anti-TB results. • Single crystal X-ray and computational photo physical studies were carried out. With the intent to discover new anti-TB compounds, new imidazopyridine analogues were synthesized through Schiff-base reaction. The newly developed imidazopyridines (I1-I8) were characterized using spectroscopic and elemental analysis. In addition the structure of compound I3 was elucidated by the single crystal X-ray diffraction technique. The global chemical reactivity descriptor parameter was calculated using theoretically DFT-B3LYP-6–31G(d) basis set which estimated HOMO-LUMO value and results are discussed. All the newly synthesized compounds were screened for their in vitro anti-tubercular activity, while the most active compounds were subjected to a cytotoxicity assay on Vero cell lines. Most of the tested compounds exhibited significant anti-TB activity with MIC in the range 3.12 – 12.5 μg/mL. Among the synthesized, compound I2 and I7 were found to be more active than the standard anti-TB drug streptomycin and comparable activity to pyrazinamide. A cytotoxicity study on Vero-cell lines confirmed the nontoxic nature of compound I2 and I7 indicating good safety profile. The molecular docking studies on PDB IB: 4ED4 enzyme of Mycobacterium tuberculosis was conducted to investigate mechanisms of anti-TB activity. The compounds displayed excellent hydrogen binding interactions and docking scores against MTB, which were in accordance with the results and further supported its credibility. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • Benzimidazole linked with imidazo[1,2- a ]pyridine molecules were synthesized by microwave irradiation. • Fluorescent properties of the molecules were determined in different solvents, aqueous media, and different acids. • 6a shows pH-sensitive fluorescence change. An approach for the synthesis of benzimidazole linked with imidazopyridine through a greener and highly efficient method is proposed herein. The approach involves the use of green, safe, and easy-to-use solvents: EtOH & H 2 O, which overthrows the already reported procedures using catalysts (Cu, Au, Zr, etc) and oxidizing agents. The efficiency of method was evaluated based on synthesis of derivatives (6a-h) containing versatile substituents. Synthesized compounds were investigated for their fluorescent properties in different solvents, aqueous medium, and different acids. 6a shows enhanced fluorescence in neutral to basic conditions and characterized by 1D & 2D NMR spectra. 6a could find application as pH-sensitive probes for the diagnosis of alkaline conditions. [ABSTRACT FROM AUTHOR]

• Several oxadiazole-based thiourea derivatives containing imidazopyridine moiety were synthesized. • Also, all derivatives were tested to determine their ability to inhibit α-amylase, α-glucosidase and 2- diphenyl-1-picrylhydrazyl (DDPH) and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging enzymes. • A molecular docking simulation of the most potent derivatives was performed to determine whether they are able to bind to the active site of targeted enzymes. A series of new imidazopyridine based oxadiazole derivatives (5a-l) were designed and synthesized. Their structures were confirmed by spectral data and then subjected to in vitro assessment including α-glucosidase, α-amylase inhibitory, and 2- diphenyl-1-picrylhydrazyl (DDPH) and 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activities. The inhibitory activity results revealed that all the synthesized analogs displayed significant α-glucosidase and α-amylase inhibition with IC 50 values of 0.90 ± 0.10 to 18.10 ± 0.20 µM (for α-glucosidase) and 1.10 ± 0.10 to 19.70 ± 0.20 µM (for α-amylase) respectively as compared to standard acarbose with IC 50 values of 11.50 ± 0.30 µM (α-glucosidase) and 12.20 ± 0.30 µM (for α-amylase).The synthesized analogs also showed significant DPPH and ABTS radical scavenging activities with IC 50 values in the range of 1.05 ± 0.05 to 4.56 ± 3.12 µM (for DDPH) and 1.15 ± 0.05 to 4.89 ± 2.89 µ M (for ABTS) respectively, incomparison to standard ascorbic acid with IC 50 = 1.83 ± 1.32 µM (for DDPH) and 1.84 ± 1.16 µM (for ABTS) respectively. After crucial analysis of varying substitution effects on inhibitory (α-glucosidase &α-amylase) and radical scavenging (DPPH & ABTS) potentials respectively, the structure-activity relationship (SAR) was established. Through the in silico molecular docking analysis, the ability of the synthesized analogs to inhibit α-glucosidase and α -amylase was also examined.There was a good correlation between in vitro and in silico studies for synthesized analogs 5i and 5d Further studies are required to determine whether these potent analogs could be a potential treatment for diabetes disease. [ABSTRACT FROM AUTHOR]

[Display omitted] • The charge transfer mechanism controls the mild steel corrosion process. • The inhibitory power of the two investigated imidazopyridine derivatives decreases with a rise in temperature. • The studied inhibitors adsorb on the mild steel surface in accordance with the Langmuir's isotherm model. • Quantum chemical calculations support experimental findings. In this study, two inhibitors namely 6-Chloro −2-phenylimidazo[1,2-a]pyridine (Pyr1) and 6-Chloro-2-(4- Chlorophenyl)imidazo[1,2-a]pyridine (Pyr2) were used to investigate their inhibition ability toward mild steel corrosion in 1 M HCl using electrochemical techniques and quantum approaches. The two inhibitors show corrosion inhibition efficiency of 98.35% and 97.57% for Pyr2 and Pyr1 respectively at the optimum concentration 10-3 M. This is due to the features of the substituent group and the effect of its emplacement in the phenyl ring. The electrochemical measurements reveal that both anodic and cathodic current are affected by these organic compounds so they are classified as mixed-type inhibitors with predominance cathodic character. The inhibited solution was analysed using UV spectrometer, which indicates a tendency to develop a complex between inhibitors and ferrous ions. The computational approaches were performed in order to examine the correlation between inhibition efficiency and molecular structure of the inhibitors Pyr1 and Pyr2. [ABSTRACT FROM AUTHOR]

[Display omitted] • The pharmaceutical significance of imidazopyridines is described. • The importance of kinases in cellular processes and their structures are presented. • The role of kinases in the cancer treatment is explained. • The comprehensive review about imidazopyridines as kinase inhibitors are provided. • The substantial structural features and interactions of imidazopyridines against these kinases are thoroughly described. Considering the fundamental role of protein kinases in the mechanism of protein phosphorylation in critical cellular processes, their dysregulation, especially in cancers, has underscored their therapeutic relevance. Imidazopyridines represent versatile scaffolds found in abundant bioactive compounds. Given their structural features, imidazopyridines have possessed pivotal potency to interact with different protein kinases, inspiring researchers to carry out numerous structural variations. In this comprehensive review, we encompass an extensive survey of the design and biological evaluations of imidazopyridine-based small molecules as potential agents targeting diverse kinases for anticancer applications. We describe the structural elements critical to inhibitory potency, elucidating their key structure–activity relationships (SAR) and mode of actions, where available. We classify these compounds into two groups: Serine/threonine and Tyrosine inhibitors. By highlighting the promising role of imidazopyridines in kinase inhibition, we aim to facilitate the design and development of more effective, targeted compounds for cancer treatment. [ABSTRACT FROM AUTHOR]

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. 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. Particularly, the analogs 4i (IC 50 = 5.68 ± 1.66 μM) , 4o (IC 50 = 7.11 ± 1.24 μM) , 4 g (IC 50 = 9.41 ± 1.19 μM) and 4 h (IC 50 = 10.45 ± 2.57 μM) were identified to be more potent than standard thiourea drug (IC 50 = 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. 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 -CF 3 & –NO 2 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. [ABSTRACT FROM AUTHOR]

New imidazopyridine-chalcone analogs were synthesized through the Claisen-Schmidt condensation reaction. The newly synthesized imidazopyridine-chalcones (S1-S12) were characterized using spectroscopic and elemental analysis. The structures of compounds S2 and S5 were confirmed by X-ray crystallography. The global chemical reactivity descriptor parameter was calculated using theoretically (DFT-B3LYP-3-211, G) estimated highest occupied molecular orbital and lowest unoccupied molecular orbital values and the results are discussed. Compounds S1-S12 were screened on A-549 (lung carcinoma epithelial cells) and MDA-MB-231 (M.D. Anderson-Metastatic Breast 231) cancer cell lines. Compounds S6 and S12 displayed exceptional antiproliferative activity against lung A-549 cancer cells with IC 50 values of 4.22 and 6.89 µM, respectively, compared to the standard drug doxorubicin (IC 50  = 3.79 μM). In the case of the MDA-MB-231 cell line, S1 and S6 exhibited exceptionally superior antiproliferative activity with IC 50 of 5.22 and 6.50 μM, respectively, compared to doxorubicin (IC 50  = 5.48 μM). S1 was found to be more active than doxorubicin. Compounds S1-S12 were tested for their cytotoxicity on human embryonic kidney 293 cells, which confirmed the nontoxic nature of the active compounds. Further molecular docking studies verified that compounds S1-S12 have a higher docking score and interacted well with the target protein. The most active compound S1 interacted well with the target protein carbonic anhydrase II in complex with pyrimidine-based inhibitor, and S6 with human Topo IIα ATPase/AMP-PNP. The results suggest that imidazopyridine-chalcone analogs may serve as new leads as anticancer agents., (© 2023 Deutsche Pharmazeutische Gesellschaft.)

Discovery of novel and potent lead molecules for the specific therapeutic targets by de novo drug design is still in infancy. Here, we disclose the unprecedented development of imidazopyri(mi)dine-based tumor pyruvate kinase M2 (PKM2) modulators by subsequent link and grow strategy. The most potent modulator 15n acts as a PKM2 activator with an AC 50 of 90 nM, with considerable cancer cell-selectivity and membrane-permeability. NMR metabolomics studies also revealed that treatment with 15n results in diminution in lactate concentrations in MCF-7 cells. 15n binds to a previously reported site at PKM2 adjacent to the interface of two monomers. In molecular dynamics (MD) simulation studies, it was observed that 15n stabilizes the PKM2 at the dimeric interface, assisting in the formation of a biologically active tetramer conformation. 15n was also screened on MCF-7 breast cancer cell lines grown on 3-D scaffolds, and the results exhibited better anticancer potential compared to control, paving the way for future clinical studies. [Display omitted] [ABSTRACT FROM AUTHOR]