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.
Background: Alzheimer's disease is rapidly becoming a major threat to public health, with an increasing number of individuals affected as the world's population ages. In this sense, studies have been carried out aiming at the identification of new small-molecule kinase inhibitors useful for the treatment of Alzheimer's disease. Objective: In the present study, we investigated the compounds developed as inhibitors of different protein kinases associated with the pathogenesis of Alzheimer's disease. Methods: The applied methodology was the use of the Clarivate Analytics Integrity and ClinicalTrials. com databases. Moreover, we highlight ROCK2 as a promising target despite being little studied for this purpose. A careful structure-activity relationship analysis of the ROCK2 inhibitors was performed to identify important structural features and fragments for the interaction with the kinase active site, aiming to rationally design novel potent and selective inhibitors. Results: We were able to notice some structural characteristics that could serve as the basis to better guide the rational design of new ROCK2 inhibitors as well as some more in-depth characteristics regarding the topology of the active site of both isoforms of these enzymes, thereby identifying differences that could lead to planning more selective compounds. Conclusion: We hope that this work can be useful to update researchers working in this area, enabling the emergence of new ideas and a greater direction of efforts for designing new ROCK2 inhibitors to identify new therapeutic alternatives for Alzheimer's disease.
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