Pyrrolopyrimidine Bumped Kinase Inhibitors for the Treatment of Cryptosporidiosis.
ACS Infect Dis
; 7(5): 1200-1207, 2021 05 14.
Article
en En
| MEDLINE
| ID: mdl-33565854
ABSTRACT
Bumped kinase inhibitors (BKIs) that target Cryptosporidium parvum calcium-dependent protein kinase 1 have been well established as potential drug candidates against cryptosporidiosis. Recently, BKI-1649, with a 7H-pyrrolo[2,3-d]pyrimidin-4-amine, or "pyrrolopyrimidine", central scaffold, has shown improved efficacy in mouse models of Cryptosporidium at substantially reduced doses compared to previously explored analogs of the pyrazolopyrimidine scaffold. Here, two pyrrolopyrimidines with varied substituent groups, BKI-1812 and BKI-1814, were explored in several in vitro and in vivo models and show improvements in potency over the previously utilized pyrazolopyrimidine bumped kinase inhibitors while maintaining equivalent results in other key properties, such as toxicity and efficacy, with their pyrazolopyrimidine isosteric counterparts.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Criptosporidiosis
/
Cryptosporidium
/
Antiprotozoarios
Límite:
Animals
Idioma:
En
Revista:
ACS Infect Dis
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos