Phenyl bioisosteres in medicinal chemistry: discovery of novel γ-secretase modulators as a potential treatment for Alzheimer's disease.
Journal
RSC medicinal chemistry
ISSN: 2632-8682
Titre abrégé: RSC Med Chem
Pays: England
ID NLM: 101759460
Informations de publication
Date de publication:
26 May 2021
26 May 2021
Historique:
received:
11
02
2021
accepted:
23
03
2021
entrez:
14
6
2021
pubmed:
15
6
2021
medline:
15
6
2021
Statut:
epublish
Résumé
Phenyl rings are one of the most prevalent structural moieties in active pharmaceutical ingredients, even if they often contribute to poor physico-chemical properties. Herein, we propose the use of a bridged piperidine (BP) moiety as a phenyl bioisostere, which could also be seen as a superior phenyl alternative as it led to strongly improved drug like properties, in terms of solubility and lipophilicity. Additionally, this BP moiety compares favorably to the recently reported saturated phenyl bioisosteres. We applied this concept to our γ-secretase modulator (GSM) project for the potential treatment of Alzheimer's disease delivering clinical candidates.
Identifiants
pubmed: 34124674
doi: 10.1039/d1md00043h
pii: d1md00043h
pmc: PMC8152580
doi:
Types de publication
Journal Article
Langues
eng
Pagination
758-766Informations de copyright
This journal is © The Royal Society of Chemistry.
Déclaration de conflit d'intérêts
There is no conflict of interest to declare.
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