Thiazolo[5,4-f]quinazolin-9-ones, inhibitors of glycogen synthase kinase-3.
Bioorg Med Chem Lett
; 16(13): 3419-23, 2006 Jul 01.
Article
in En
| MEDLINE
| ID: mdl-16644220
ABSTRACT
In an effort to identify new protein kinase inhibitors with increased potency and selectivity, we have developed the microwave-assisted synthesis of thiazolo[5,4-f]quinazolin-9-ones. The effects of eighteen derivatives on CDK1/cyclin B, CDK5/p25, and GSK-3 were investigated. Several turned out to inhibit GSK-3 in the micromolar range. Molecular modeling studies suggest that the most selective GSK-3 inhibitors 7a-d bind into the ATP-binding site through a key hydrogen bond interaction with Val135 and target the specific hydrophobic backpocket of the enzyme.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Quinazolines
/
Thiazoles
/
Glycogen Synthase Kinase 3
/
Enzyme Inhibitors
Language:
En
Journal:
Bioorg Med Chem Lett
Journal subject:
BIOQUIMICA
/
QUIMICA
Year:
2006
Document type:
Article
Affiliation country:
France