Indole amide derivatives in Alzheimer’s disease: advancing from synthesis to drug discovery

In the field of organic synthesis, the indole ring - a biologically significant heterocycle - plays a pivotal role, particularly in electrophilic substitution reactions, predominantly at position 3. Given its importance, numerous reviews have been published in recent years, detailing both the synthesis and the broad spectrum of biological activities associated with the indole scaffold. This article aims to compile and critically analyze key bibliographic reports published between 2017 and 2025, with a particular focus on contributions to medicinal chemistry, specifically in the context of compounds relevant to Alzheimer’s disease. This review presents the primary methodologies employed in the synthesis of indole amide derivatives, highlighting eleven distinct synthetic approaches reported in the literature. Furthermore, molecular modeling studies were performed on five indole amides selected from the reviewed references within the specified timeframe. Among these, one reference was specifically utilized in a molecular docking analysis, providing insights into a potential mechanism of action through acetylcholinesterase inhibition. Based on the most relevant studies, five recently investigated indole amides were selected for molecular docking studies, which elucidated their key interactions with the acetylcholinesterase enzyme. These findings reinforce the importance of indole amides as a promising class of compounds for the development of novel therapeutic agents targeting Alzheimer’s disease.