Novel heterocyclic nitrofurfural hydrazones. In vivo antirypanosomal activity.
J Med Chem
; 19(4): 512-6, 1976 Apr.
Article
en En
| MEDLINE
| ID: mdl-817023
Hydrazine derivatives of several pyrazolo[1,5-alpha]pyrimidines (A), pyrazolo[1,5-alpha]-1,3,5-triazines (B), s-triazolo[1,5-alpha]pyrimidines (C), and imidazo[1,2-alpha]pyrimidines (D) were synthesized and condensed with 5-nitrofurfural in order to obtain the corresponding nitrofurfural hydrazones of each heterocycle (1d-14d). Each compound was screened for in vitro activity against Trypanosoma cruzi. The compounds were then tested in vivo against experimental infections of T. cruzi in laboratory (C3H/He strain) mice. An interesting structure-activity relationship was uncovered, revealing that 5-methyl-7-(5-nitrofurfurylidenehydrazino)pyrazolo[1,5-alpha]pyrimidine (2d) greatly increased the mean survival time (IMST) of mice with terminal infections. Subtle alterations in the structure of 2d, such as the substitution of a 5-hydrogen for the 5-methyl group (1d) or the substitution of the 3-hydrogen by the water-soluble 3-sulfonic acid (3d) or 3-sodium sulfonate (4d), resulted in a drastic loss of in vivo and in vitro activity.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Tripanocidas
/
Nitrofuranos
Límite:
Animals
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
1976
Tipo del documento:
Article
Pais de publicación:
Estados Unidos