Imidazo[1,2-b]pyridazines as inhibitors of DYRK kinases.
Eur J Med Chem
; 269: 116292, 2024 Apr 05.
Article
in 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pyridazines
/
Iohexol
/
Diabetes Mellitus, Type 2
Limits:
Humans
Language:
En
Journal:
Eur J Med Chem
Year:
2024
Document type:
Article