Novel thienopyrimidones targeting hepatic and erythrocytic stages of Plasmodium parasites with increased microsomal stability.
Journal
European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510
Informations de publication
Date de publication:
05 Dec 2023
05 Dec 2023
Historique:
received:
03
07
2023
revised:
02
10
2023
accepted:
11
10
2023
medline:
3
11
2023
pubmed:
20
10
2023
entrez:
19
10
2023
Statut:
ppublish
Résumé
Based on the structure of a previously identified hit, Gamhepathiopine 1, which showed promising antiplasmodial activity, but poor microsomal stability, several strategies were investigated to improve the metabolic stability of the compounds. This included the introduction of fluorine or deuterium atoms, as well as carbocyclic groups. Among the new compounds, the 2-aminocyclobutyl derivative 5g demonstrated enhanced microsomal stability compared to compound 1, while retaining antiplasmodial activity against erythrocytic and hepatic stages of Plasmodium, without significant cytotoxicity against primary hepatocytes.
Identifiants
pubmed: 37857143
pii: S0223-5234(23)00840-1
doi: 10.1016/j.ejmech.2023.115873
pii:
doi:
Substances chimiques
Antimalarials
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
115873Informations de copyright
Copyright © 2023 Elsevier Masson SAS. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.