Synthesis of novel huprine derivatives as potential cholinesterase inhibitors

• Main Author: Pokrievková, Lucia
• Other Authors: Roh, Jaroslav
• Format: Dissertation
• Language: Slovak
• Published: 2018
• Online Access: http://www.nusl.cz/ntk/nusl-388311

Charles University Faculty of Pharmacy in Hradec Králové Department of Organic And Bioorganic Chemistry Student: Lucia Pokrievková Supervisor: doc. PharmDr. Jaroslav Roh, Ph.D. Supervisor specialist: RNDr. Eva Mezeiová, Ph.D., PharmDr. Jan Korábečný, Ph.D. Title of Diploma thesis: Synthesis of novel huprine derivatives as potential cholinesterase inhibitors Alzheimer's disease (AD) is a complex neurodegenerative disease that is manifested by the gradual loss of short-term and, at more advanced stages, also of long-term memory. The characteristic histopathological features of AD is the presence of neuritic plaques and neurofibrillary tangles in affected brain regions. Cholinergic neurotransmission is also one of the key pathological findings in AD. Only two drug groups are used in AD therapy. The first group consists of acetylcholinesterase inhibitors (AChEIs). Memantine, which is a glutamate receptors antagonist, belongs to the second one. The aim of the diploma thesis was the synthesis of a new group of drugs acting as multipotent ligands (multi-target directed ligands, MTDLs) derived from huprines. The new compounds were designed to be able to interact with both anionic sites of acetylcholinesterase (AChE), thereby exaggerating the enzyme-inhibiting effect. In the experimental part of the diploma...