2-Phenylimidazo[1,2-a]pyridine-3-carboxylic Acid Derivatives: Synthesis and Antiinflammatory Activity

Abdollahi Kheradmand Y., Salimi F., Oji Moghanlou A.

Recently, the development of supported ionic liquid on magnetic nanoparticles (MNP) and multicomponent reactions in industry and academia has been a matter of intense study. In this new and environmentally benign synthetic methodology, a dihydroxyl functionalized basic ionic liquid precursor was immobilized onto the magnetic silica nanoparticles via covalent bonding to prepare a novel powerful basic catalyst (DHBIL@Si-MNPs). The synthesized catalyst was characterized extensively by various techniques. Also, the alkalinity of the DHBIL@Si-MNPs catalyst (pKb value) was obtained at 9.23. The catalytic activity of the prepared catalyst was investigated in a one-pot and three-component reaction between pyridine, phenacyl bromide, and thiocyanate to afford corresponding substituted imidazo [1,2-a] Pyridine derivatives under solvent-free conditions. Different spectroscopic methods were used to establish the structures of target compounds. The imidazopyridines were generated in excellent yields (80–98%) under the optimum conditions utilizing 10% by weight of DHBIL@Si-MNPs to pyridine, a molar ratio of 1.2: 1.2: 1 mmol (mmol), and a temperature of 100 °C. The present developed synthetic protocol permits the production of interesting medicinal compounds with high purity and different functional group tolerating abilities. Also, the other significant advantages of this protocol are highlighted by less reaction time, cleaner reaction profiles, avoidance of toxic catalysts, simplicity of the process, benign reaction conditions, use of available raw materials, and easy separation of products. The catalyst could be easily recycled from the reaction mixture using an external magnet thanks to its superparamagnetic and reused several times without any appreciable decrease in its reactivity and product yield.

Moazzam A., Farid S.M., Khaleghi N., Alizadeh N., Mahdavi M.

This communication describes the development of a mild method for the arylation of imidazo[1,2-a]pyridine with diazonium salt derivatives and using chlorophyll as a biocatalyst via visible-light catalysis.

Khatun S., Singh A., Bader G.N., Sofi F.A.

Imidazopyridine scaffold has gained tremendous importance over the past few decades. Imidazopyridines have been expeditiously used for the rationale design and development of novel synthetic analogs for various therapeutic disorders. A wide variety of imidazopyridine derivatives have been developed as potential anti-cancer, anti-diabetic, anti-tubercular, anti-microbial, anti-viral, anti-inflammatory, central nervous system (CNS) agents besides other chemotherapeutic agents. Imidazopyridine heterocyclic system acts as a key pharmacophore motif for the identification and optimization of lead structures to increase medicinal chemistry toolbox. The present review highlights the medicinal significances of imidazopyridines for their rationale development as lead molecules with improved therapeutic efficacies. This review further emphasis on the structure-activity relationships (SARs) of the various designed imidazopyridines to establish a relationship between the key structural features versus the biological activities.Communicated by Ramaswamy H. Sarma.

Wan Y., Wu H., Ma N., Zhao J., Zhang Z., Gao W., Zhang G.

Described here is the de novo design and synthesis of a series of 6H-dipyrido[1,2-e:2',1'-i]purin-6-ones (DPs) as a new class of visible-light photoredox catalysts (PCs). The synthesized DP1-5 showed their λAbs(max) values in 433-477 nm, excited state redox potentials in 1.15-0.69 eV and -1.41 to -1.77 eV (vs. SCE), respectively. As a representative, DP4 enables the productive guanylation of various amines, including 1°, 2°, and 3°-alkyl primary amines, secondary amines, aryl and heteroaryl amines, amino-nitrile, amino acids and peptides as well as propynylamines and α-amino esters giving diversities in biologically important guanidines and cyclic guanidines. The photocatalytic efficacy of DP4 in the guanylation overmatched commonly used Ir and Ru polypyridyl complexes, and some organic PCs. Other salient merits of this method include broad substrate scope and functional group tolerance, gram-scale synthesis, and versatile late-stage derivatizations that led to a derivative 81 exhibiting 60-fold better anticancer activity against Ramos cells with the IC50 of 0.086 μM than that of clinical drug ibrutinib (5.1 μM).

Rezvanian A., Noorakhtar F., Ziarani G.M., Mahajer F.

A green and convenient procedure for the synthesis of quinoline-conjugated imidazopyridines and pyridopyrimidines has been developed by a simple one-pot reaction in the absence of any transition metal catalyst in water. This green process can be readily performed by reacting inexpensive starting materials of 2-chloroquinoline-3-carbaldehyde, malononitrile, 1,1-bis(methylthio)-2-nitroethylene, and diamine in aqueous solution. The present synthesis shows attractive characteristics, such as the use of water as reaction media, convenient one-pot operation, and reduced waste production without the use of any base or metal promoters. The products are purified by crystallization from ethanol, and the process does not involve any hazardous solvent. Also, the fluorescence study of these conjugated systems was also considered, which revealed that they have highly selective sensing of fluoride.

Alizadeh A., Roosta A., Rezaiyehraad R.

An expeditious metal-free heteroannulation reaction for pyrido[1,2-a]pyrimidines/imidazo[1,2-a]pyridines was developed in green solvent under mild reaction conditions by using three-component reaction of 2-chloroquinoline-3-carbaldehyde, malononitrile and nitroketen aminals, which obtained from the reaction between 1,1-bis(methylthio)-2-nitroethylene and diamines in green solvent under EtOH reflux conditions. This one-pot strategy is very simple and occurs in two steps. The present sequence is visualized as an environmentally benign process with excellent purity and high yields. An efficient, useful and general procedure for the synthesis of pyrido[1,2-a]pyrimidines/imidazo[1,2-a]pyridines via a one-pot three-component reaction of 2-chloroquinoline-3-carbaldehyde, malononitrile/ethyl 2-cyanoacetate and nitroketen aminals under mild and catalyst-free conditions in excellent yields is described. The major advantages of this protocol are high yields, mild and catalyst-free conditions, short reaction times and application of green solvent.

Bakhta S., Kabri Y., Crozet M.D., Nedjar-Kolli B., Vanelle P.

A series of imidazo[1,2-a]pyridinylpropenenitriles were synthesized via consecutive one-pot Suzuki–Miyaura and Knoevenagel reactions in water/ethanol mixture between imidazo[1,2-a]pyridine-2-carbal...

Hosseini H., Bayat M.

An easy synthesis of novel and highly substituted imidazo[1,2-a]pyridines and pyrido[1,2-a]pyrimidines using heterocyclic ketene aminals.

Hosseini H., Bayat M.

A new class of tetrahydroimidazo[1,2-a]pyridine derivatives has been successfully prepared via a five-component domino reaction using cyanoacetohydrazide, 9-fluorenone, aromatic aldehydes, 1,1-bis(methylthio)-2-nitroethene and ethylenediamine in ethanol at reflux.

Jadhav S.A., Shioorkar M.G., Chavan O.S., Sarkate A.P., Shinde D.B.

ABSTRACTAn effective, expeditious, environmentally benign one-pot synthesis of 2-phenylimidazo[1,2-a]pyridines and 2-phenylimidazo[1,2-a]quinoline from easily available starting materials as aromatic carbonyl compound, 2-amino pyridine, succinamide, and in situ generated α-iodo acetophenone in combination with green solvent PEG-400 and water (2:1) under microwave irradiation. The newly developed protocol with excellent yield of product in very short time of reaction by avoiding the use of lachrymatric α-chloro and α-bromocarbonyl compounds, volatile, toxic organic and hazardous solvents, reagents is the advantage of this research work. The final products were confirmed by their characterization data such as 1H NMR, 13C NMR, high resolution mass spectrometry (HRMS) and were compared with its reported method.

Zali-Boeini H., Norastehfar N., Amiri Rudbari H.

A novel efficient and convenient synthesis of imidazo[1,2-a]pyridines in water has been developed.

Sarkar A., Santra S., Kundu S.K., Hajra A., Zyryanov G.V., Chupakhin O.N., Charushin V.N., Majee A.

Particular success has been achieved in the synthesis of new products and in processes since the twelve principles of “green chemistry” were formulated in the 1990s. These products and processes are more compatible with human health, society, and the environment. In this review, a collection of research reports have been documented from the viewpoint of green chemistry. The main theme of this review is neat reactions, which are solvent and catalyst-free reactions. Neat reactions in the absence of any solvent or catalyst with concise summaries of microwave, ball milling, and neat reactions have been described.

Babu B.M., Kumar G.S., Thakur P.B., Bangade V.M., Meshram H.M.

A mild and novel approach is described for the synthesis of functionalized fused imidazole analogues in solvent-free and catalyst-free condition in ionic liquid. The short reaction time, good isolated yields, generality and environmentally benign reaction media are the significant features of this protocol.

Marandi G., Saghatforoush L., Mendoza-Meroño R., García-Granda S.

Financial support was provided by the Research Council of Urmia University, Payame Noor University, the Ministerio de Economia Competitividad de Espana (MAT2010-15094, Factoria de Cristalizacion–Consolider Ingenio 2010), and ERDF.

Attanasi O.A., Bianchi L., Campisi L.A., Crescentini L.D., Favi G., Mantellini F.

A very simple domino reaction under solvent-free conditions of various pyridine-like heterocycles with 1,2-diaza-1,3-dienes produces in good yields imidazo[1,2-a]pyridines, imidazo[1,2-a]quinolines, and imidazo[2,1-a]isoquinolines. The advantage of this one-pot transformation lies in the use of simple pyridine-like compounds without prefunctionalization of the starting heterocycles.