Imidazole: Synthesis, Functionalization and Physicochemical Properties of a Privileged Structure in Medicinal Chemistry

Abstract

Imidazole was first synthesized by Heinrich Debus in 1858 and was obtained by the reaction of glyoxal and formaldehyde in ammonia, initially called glyoxaline. The current literature provides much information about the synthesis, functionalization, physicochemical characteristics and biological role of imidazole. Imidazole is a structure that, despite being small, has a unique chemical complexity. It is a nucleus that is very practical and versatile in its construction/functionalization and can be considered a rich source of chemical diversity. Imidazole acts in extremely important processes for the maintenance of living organisms, such as catalysis in enzymatic processes. Imidazole-based compounds with antibacterial, anti-inflammatory, antidiabetic, antiparasitic, antituberculosis, antifungal, antioxidant, antitumor, antimalarial, anticancer, antidepressant and many others make up the therapeutic arsenal and new bioactive compounds proposed in the most diverse works. The interest and importance of imidazole-containing analogs in the field of medicinal chemistry is remarkable, and the understanding from the development of the first blockbuster drug cimetidine explores all the chemical and biological concepts of imidazole in the context of research and development of new drugs.

Green Synthesis Approaches toward Preparation of ZIF-76 and Its Thermal Behavior

“…The additional 1 H NMR spectra (Figure S-8) show that the obtained ligand ratio is 1:1.7, again lower than expected from the synthesis ratio, which could be explained by linker acidity. Because the 5-ClbIm linker has a lower p K a value than the imidazole linker, , it is more acidic and thus more susceptible to deprotonation. This deprotonation makes it easier for the linker to form a stable 1:1 product because the deprotonated species can interact with other species in the system more effectively, resulting in a more stable framework.…”

Synergistic Antimicrobial Activity of Silver Nanoparticles with an Emergent Class of Azoimidazoles

“…In another field, for the purpose of producing more potent antimicrobial structures, a variety of heteroaromatic moieties have been studied. N -heterocycle scaffolds, such as imidazole rings, are readily available in nature and provide interesting biological functions such as antifungal, antibacterial, and anticancer activity [ 23 , 24 , 25 , 26 , 27 , 28 ]. In our research group, an unusual class of azo dyes containing 2-aminoimidazoles (AzoIz) was developed using 5-aminoimidazole 4-carboxamidrazones (Amz) as a precursor [ 29 , 30 ].…”

Design, Synthesis and Bioactivity Evaluation of Novel 2-(pyrazol-4-yl)-1,3,4-oxadiazoles Containing an Imidazole Fragment as Antibacterial Agents

“…Imidazole alkaloids, a common class of five-membered aromatic heterocyclic compounds containing two intersite nitrogen atoms, exist widely in plants, animals, microorganisms and marine organisms [ 1 ]. Imidazole is a dominant skeleton in drug development that exists in the core structure of many medicines and pesticides and has been extensively explored by scientific researchers [ 2 , 3 ]. As a good pharmacodynamic group, imidazole can synergically enhance drug efficacy, improve in vitro and in vivo bioactivity, and reduce biotoxicity, and it also possesses excellent bioavailability, good tissue penetration and relatively low adverse reactions [ 1 , 2 , 3 ].…”

“…Imidazole is a dominant skeleton in drug development that exists in the core structure of many medicines and pesticides and has been extensively explored by scientific researchers [ 2 , 3 ]. As a good pharmacodynamic group, imidazole can synergically enhance drug efficacy, improve in vitro and in vivo bioactivity, and reduce biotoxicity, and it also possesses excellent bioavailability, good tissue penetration and relatively low adverse reactions [ 1 , 2 , 3 ]. To date, imidazoles have become one of the most important skeletons in medicine and pesticide discovery, and many novel bioactive molecules have been reported based on this advantageous framework, such as antibacterial [ 4 , 5 ], antifungal [ 6 ], antiviral [ 7 ], anti-inflammatory [ 8 ], anticancer [ 9 ], antioxidant [ 10 ] and anti-Alzheimer’s disease [ 11 ].…”