1.
Bioorg Med Chem Lett
; 18(20): 5456-9, 2008 Oct 15.
Article
in English
| MEDLINE
| ID: mdl-18835164
ABSTRACT
We have identified a second series of potent p38 inhibitors. As with our first generation series, these compounds are based on an alpha-ketoamide scaffold. The reversal of the ketoamide order, however, introduces more chemical flexibility and in addition results in improve potencies against p38.
Subject(s)
Amides/chemistry , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Ketones/chemistry , p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors , Allosteric Site , Anti-Inflammatory Agents/pharmacology , Chemistry, Pharmaceutical/methods , Cytokines/metabolism , Drug Design , Humans , Inflammation/drug therapy , Inhibitory Concentration 50 , Models, Chemical , Models, Molecular , Structure-Activity Relationship
2.
Bioorg Med Chem Lett
; 18(12): 3578-81, 2008 Jun 15.
Article
in English
| MEDLINE
| ID: mdl-18502127
ABSTRACT
The discovery of two classes of pyrimidine-based inhibitors of GSK-3 is described. Optimization of these series led to inhibitors with IC(50)<10nM and >100-fold selectivity over Aurora A kinase. A proposed binding mode of 21b is presented. One compound (33) of the pyrimidine series showed promising pharmacokinetic parameters.