1.
Bioorg Med Chem Lett
; 20(7): 2344-9, 2010 Apr 01.
Article
in English
| MEDLINE
| ID: mdl-20189807
ABSTRACT
From potent and selective inhibitors of GSK3beta displaying CYP1A2 inhibition and poor PK properties, mostly linked to metabolic instability and in vivo hydrolysis of the amide bond, we were able to obtain safe and orally available inhibitors with good half lives.
Subject(s)
Glycogen Synthase Kinase 3/antagonists & inhibitors , Glycogen Synthase Kinase 3/metabolism , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/pharmacokinetics , Animals , Cytochrome P-450 CYP1A2/metabolism , Cytochrome P-450 CYP1A2 Inhibitors , Glycogen Synthase Kinase 3 beta , Humans , Mice , Models, Molecular , Protein Kinase Inhibitors/chemistry
2.
Bioorg Med Chem Lett
; 20(6): 1985-9, 2010 Mar 15.
Article
in English
| MEDLINE
| ID: mdl-20167481
ABSTRACT
From an HTS hit, a series of potent and selective inhibitors of GSK3beta have been designed based on a Cdk2-homology model and with the help of several crystal structures of the compounds within Cdk2.