Turning Donepezil into a Multi-Target-Directed Ligand through a Merging Strategy
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F21%3A00557423" target="_blank" >RIV/60162694:G44__/21:00557423 - isvavai.cz</a>
Alternative codes found
RIV/00179906:_____/21:10421371
Result on the web
<a href="https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.202000484" target="_blank" >https://chemistry-europe.onlinelibrary.wiley.com/doi/epdf/10.1002/cmdc.202000484</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/cmdc.202000484" target="_blank" >10.1002/cmdc.202000484</a>
Alternative languages
Result language
angličtina
Original language name
Turning Donepezil into a Multi-Target-Directed Ligand through a Merging Strategy
Original language description
Thanks to the widespread use and safety profile of donepezil (1) in the treatment of Alzheimer's disease (AD), one of the most widely adopted multi-target-directed ligand (MTDL) design strategies is to modify its molecular structure by linking a second fragment carrying an additional AD-relevant biological property. Herein, supported by a proposed combination therapy of1and the quinone drug idebenone, we rationally designed novel1-based MTDLs targeting A beta and oxidative pathways. By exploiting a bioisosteric replacement of the indanone core of1with a 1,4-naphthoquinone, we ended up with a series of highly merged derivatives, in principle devoid of the "physicochemical challenge" typical of large hybrid-based MTDLs. A preliminary investigation of their multi-target profile identified9, which showed a potent and selective butyrylcholinesterase inhibitory activity, together with antioxidant and antiaggregating properties. In addition, it displayed a promising drug-like profile.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30107 - Medicinal chemistry
Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
S - Specificky vyzkum na vysokych skolach
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
ChemMedChem
ISSN
1860-7179
e-ISSN
1860-7187
Volume of the periodical
16
Issue of the periodical within the volume
1
Country of publishing house
DE - GERMANY
Number of pages
12
Pages from-to
187-198
UT code for WoS article
000564570900001
EID of the result in the Scopus database
2-s2.0-85089982454