Benzofuran and Indole: Promising Scaffolds for Drug Development in Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease with no clinically accepted treatment to cure or halt its progression. The Food and Drug Administration has approved drugs (e.g., rivastigmine, donepezil, galantamine, and memantine) that at best provide marginal benefits, thus emphasizing the urgent need to explore other molecular entities as future drug candidates for AD. Looking at the wide pharmaceutical applications of heterocyclic compounds and particularly those containing benzofuran and indole ring systems, these molecular frameworks have drawn special attention from medicinal chemists for further evaluation in numerous diseases. This article focuses on the history and recent advances of benzofuran- and indole-based compounds as inhibitors of butyrylcholinesterase, acetylcholinesterase, γ-secretase, β-secretase, tau misfolding, and β-amyloid aggregation.

Harnessing the Chemistry of the Indole Heterocycle to Drive Discoveries in Biology and Medicine

“…Numerous indole-containing natural products [1][2][3][4][5][6] and synthetic compounds [7][8][9][10][11] demonstrate biological activities of importance to human disease. These biological activities are driven by intricate molecular interactions between the indole agent and its corresponding therapeutic target that controls disease.…”

Application of Electrochemical Processes to Classical Iodocyclisation: Utility for Selectivity and Mechanistic Insight

“…Iodocyclisation of alkenes with oxygen nucleophiles is a powerful method of generating furan and benzofuran frameworks that maintain the iodine functionality and thereby allow further manipulation . The benzofuran motif is an important framework in a variety of natural products and drug substances and as such, rapid and efficient processes for the construction of substituted variants via the construction of the bicyclic nucleus are synthetically valuable . With our own research interests in practical electrochemical processes we here report an efficient route for the construction of the dihydrobenzofuran framework through an iodoetherification reaction of 2‐allylphenols where the molecular iodine and a Lewis acid are electrochemically generated from benign starting materials.…”

“…[1][2][3][4][5] The benzofuran motif is an important framework in a variety of natural products and drug substances and as such, rapid and efficient processes for the construction of substituted variants via the construction of the bicyclic nucleus are synthetically valuable. [6][7][8][9][10][11][12][13] With our own research interests in practical electrochemical processes we here report an efficient route for the construction of the dihydrobenzofuran framework through an iodoetherification reaction of 2-allylphenols where the molecular iodine and a Lewis acid are electrochemically generated from benign starting materials. Examples of iodocyclisation of phenols onto alkenes are conspicuously sparse in the literature with only a few examples being noted.…”

A Simple and Efficient Process for the Synthesis of Novel Heterocycles Containing Benzofuran Moiety Using Thiocarbohydrazide as a Precursor

“…The chemistry of benzofurans has attracted the attention of researchers in both academia and industry due to their wide range of biological activities and their presence in many natural products . Various benzofurans showed antibacterial , antioxidant , anti‐inflammatory , cholinesterase inhibition , antidepressant , anticonvulsant , and anticancer activities .…”

“…(Benzofuran-2-yl)ethylidene) hydrazinecarbothiohydrazide(3). A mixture of 1 (0.80 g, 5.0 mmol) and 2 (0.53 g, 5.0 mmol) in dry EtOH (30 mL) containing glacial AcOH (0.3 mL) was refluxed for 3 h. The solid obtained on cooling was filtered, dried, and recrystallized from dimethylformamide (DMF) to give yellow crystals of 3 in 86% yield, mp 250-252°C 1.…”