Synthesis and pharmacological evaluation of novel tacrine derivatives as potential acetylcholinesterase inhibitors

Abstract

Alzheimer's disease (AD) is a progressive, neurodegenerative disorder characterized by deterioration of cognitive skills and it is the most abundant form of dementia according to the World Health Organization (WHO).1 Tacrine belongs to a class of acetylcholinesterase inhibitors (AChEIs) and it was formerly used in the treatment of AD symptoms. Albeit no longer in clinical use due to its hepatotoxicity, tacrine ring system is extensively investigated as pharmacophore in novel AChEIs, many of which showed improved pharmacological profile in the preclinical studies.2 Here we present optimized synthetic pathway and pharmacological evaluation of three novel tacrine derivatives (5, 6 and 7), possessing functionalized piperidine connected with tacrine via five methylene groups alkyl chain