Synthetic Approaches for Piperidone-Based Templates as Scaffolds to Access Chirally Enriched Donepezil Analogues

Autor:	Agostino Cilibrizzi, David M. Mountford, Anna Poeschl, Robert C. Hider
Jazyk:	angličtina
Rok vydání:	2020
Předmět:	Chemistry General Chemical Engineering Diastereomer General Chemistry Combinatorial chemistry Acetylcholinesterase Article chemistry.chemical_compound Template mental disorders medicine Moiety Piperidine Donepezil QD1-999 Biological evaluation medicine.drug
Zdroj:	ACS Omega, Vol 5, Iss 5, Pp 2378-2396 (2020) ACS Omega
ISSN:	2470-1343
Popis:	A concise and high-yielding double aza-Michael reaction is presented as an atom-efficient method to access chiral 2-substituted 4-piperidone building blocks from divinyl ketones. The piperidones were further converted into analogues of donepezil, an acetylcholinesterase inhibiting drug used in the treatment of Alzheimer’s disease. The donepezil analogues were obtained as inseparable diastereomeric mixtures with resolved stereochemistry in position 2 of the piperidine ring. Biological evaluation of the acetylcholinesterase inhibition by these analogues provides a new insight into structure–activity relationship studies with regard to donepezil’s piperidine moiety toward stereochemical enhancement.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c8aabba3a8289cbde421321ff08b314e https://doaj.org/article/745bb46d814c4a76bef761f5369fd2c3 Zobrazit plný text záznamu