Discovery of acyl ureas as highly selective small molecule CSF1R kinase inhibitors.
Bioorg Med Chem Lett
; 74: 128929, 2022 10 15.
Article
in En
| MEDLINE
| ID: mdl-35961461
ABSTRACT
Based on the structure of an early lead identified in Deciphera's proprietary compound collection of switch control kinase inhibitors and using a combination of medicinal chemistry guided structure activity relationships and structure-based drug design, a novel series of potent acyl urea-based CSF1R inhibitors was identified displaying high selectivity for CSF1R versus the other members of the Type III receptor tyrosine kinase (RTK) family members (KIT, PDGFR-α, PDGFR-ß, and FLT3), VEGFR2 and MET. Based on in vitro biology, in vitro ADME and in vivo PK/PD studies, compound 10 was selected as an advanced lead for Deciphera's CSF1R research program.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Urea
/
Receptor Protein-Tyrosine Kinases
Type of study:
Prognostic_studies
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2022
Document type:
Article
Affiliation country: