Synthesis of Novel Oxime and Benzofuran Chemical Frameworks Possessing Potent Anticholinesterase Activity: A SAR Study Related to Alzheimer Disease

Abstract

Alzheimer Disease (AD) is a neurological disorder that causes the brain to shrink and brain cells to eventually die. Main symptom of AD is dementia. Today, approximately 50 million people worldwide are estimated to have AD. However, there is not a determined cure known against AD today. There are just four drugs against AD on the market. Unfortunately, none of them can totally destroy AD. Thus, discovering new molecules having capability to treat AD is required and significant. Benzofurans and oximes demonstrate a number of biological effects including anti‐inflammatory and brain‐barrier penetrating. For this reason, a number of novel compounds bearing oxime and benzofuran skeletons were designed and synthesized, and their anticholinesterase activities were investigated. Based on the results, several molecules demonstrated very strong anticholinesterase activities against both AChE and BChE enzymes, even much better than the reference drug molecule, Galantamine. Besides, structure‐activity relationship (SAR) studies belonging to these chemical cores were revealed through this study for the first time. Various derivatives with different types of selective activities were obtained, which brightens the detailed SAR tendency of these molecules. This study can contribute to discover a novel lead drug molecule against AD, which is an urgent need.