Imidazo[1,2-b]pyridazines as inhibitors of DYRK kinases.
Eur J Med Chem
; 269: 116292, 2024 Apr 05.
Article
en En
| MEDLINE
| ID: mdl-38479168
ABSTRACT
Selective inhibitors of DYRK1A are of interest for the treatment of cancer, Type 2 diabetes and neurological disorders. Optimization of imidazo [1,2-b]pyridazine fragment 1 through structure-activity relationship exploration and in silico drug design efforts led to the discovery of compound 17 as a potent cellular inhibitor of DYRK1A with selectivity over much of the kinome. The binding mode of compound 17 was elucidated with X-ray crystallography, facilitating the rational design of compound 29, an imidazo [1,2-b]pyridazine with improved kinase selectivity with respect to closely related CLK kinases.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Piridazinas
/
Yohexol
/
Diabetes Mellitus Tipo 2
Límite:
Humans
Idioma:
En
Revista:
Eur J Med Chem
Año:
2024
Tipo del documento:
Article