Synthesis of functionalized derivatives of the gamma-secretase modulator BMS-932481 and identification of its major metabolite.
Alzheimer's disease
GS modulators
Metabolites
Journal
Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377
Informations de publication
Date de publication:
15 11 2020
15 11 2020
Historique:
received:
08
04
2020
revised:
21
08
2020
accepted:
27
08
2020
pubmed:
6
9
2020
medline:
23
6
2021
entrez:
5
9
2020
Statut:
ppublish
Résumé
In an effort to improve physical properties by introducing polar functionality into the bicyclic pyrimidine gamma-secretase modulator (GSM) clinical candidate BMS-932481, we prepared several oxidative products of BMS-932481. Among the analogs that were prepared, the C-5 alcohol 3 was identified as the predominant metabolite of BMS-932481 found in rat and human liver microsomes. Alcohol 3 was determined to be chemically unstable, leading to the hypothesis that 3 may lead to the production of reactive species both in vitro and in vivo.
Identifiants
pubmed: 32890687
pii: S0960-894X(20)30641-7
doi: 10.1016/j.bmcl.2020.127530
pii:
doi:
Substances chimiques
7-(4-fluorophenyl)-N2-(3-methoxy-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)-N4-methyl-6,7-dihydro-5H-cyclopenta(d)pyrimidine-2,4-diamine
0
Aniline Compounds
0
Pyrimidines
0
Amyloid Precursor Protein Secretases
EC 3.4.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
127530Informations de copyright
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