Structure-based optimization of 1H-imidazole-2-carboxamides as Axl kinase inhibitors utilizing a Mer mutant surrogate.
Bioorg Med Chem Lett
; 27(4): 1099-1104, 2017 02 15.
Article
in En
| MEDLINE
| ID: mdl-28082036
ABSTRACT
Axl has been a target of interest in the oncology field for several years based on its role in various oncogenic processes. To date, no wild-type Axl crystal structure has been reported. Herein, we describe the structure-based optimization of a novel chemotype of Axl inhibitors, 1H-imidazole-2-carboxamide, using a mutated kinase homolog, Mer(I650M), as a crystallographic surrogate. Iterative optimization of the initial lead compound (1) led to compound (21), a selective and potent inhibitor of wild-type Axl. Compound (21) will serve as a useful compound for further in vivo studies.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Proto-Oncogene Proteins
/
Receptor Protein-Tyrosine Kinases
/
Protein Kinase Inhibitors
/
Imidazoles
/
Mutation
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2017
Document type:
Article