New antiplasmodial 4-amino-thieno[3,2-d]pyrimidines with improved intestinal permeability and microsomal stability - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue European Journal of Medicinal Chemistry Année : 2023

New antiplasmodial 4-amino-thieno[3,2-d]pyrimidines with improved intestinal permeability and microsomal stability

Romain Mustière
  • Fonction : Auteur
  • PersonId : 1100729

Résumé

The increasing number of Plasmodium falciparum strains resistant to current treatments justifies the urgent need to discover new compounds active on several stages of the parasite development. Based on the structure of Gamhepathiopine, a 2-tert-butylaminothieno[3,2-d]pyrimidin-4(3H)-one previously identified for its dual activity against the sexual and asexual stages of P. falciparum, 25 new 4-amino-substituted analogues were synthesized and evaluated on the erythrocytic and hepatic stages of Plasmodium. A promising compound, N2-(tert-butyl)-N [4]-(3-(dimethylamino)propyl)-6-(p-tolyl)thieno[3,2-d]pyrimidine-2,4-diamine, showed improved physicochemical properties, intestinal permeability (PAMPA model) and microsomal stability compared to Gamhepathiopine, while maintaining a good antiplasmodial activity on the erythrocytic stage of P. falciparum and on the hepatic stage of P. berghei.
Fichier non déposé

Dates et versions

hal-03942426 , version 1 (17-01-2023)

Identifiants

Citer

Prisca Lagardère, Romain Mustière, Nadia Amanzougaghene, Sébastien Hutter, Marion Casanova, et al.. New antiplasmodial 4-amino-thieno[3,2-d]pyrimidines with improved intestinal permeability and microsomal stability. European Journal of Medicinal Chemistry, 2023, 249, pp.115115. ⟨10.1016/j.ejmech.2023.115115⟩. ⟨hal-03942426⟩
37 Consultations
0 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More