1.
Bioorg Med Chem Lett
; 13(18): 3105-10, 2003 Sep 15.
Article
in English
| MEDLINE
| ID: mdl-12941344
ABSTRACT
The utilization and impact of parallel synthesis on lead exploration around initial hit oxindole (1) are described. The emergent SAR, analogue design and functional impact will also be detailed.
Subject(s)
Adjuvants, Immunologic/chemistry , Protein-Tyrosine Kinases/chemistry , Protein-Tyrosine Kinases/immunology , Animals , Binding Sites , Cell Division/drug effects , Drug Design , Edema/drug therapy , Enzyme Inhibitors/chemistry , Indoles/chemistry , Inhibitory Concentration 50 , Interleukin-2/pharmacology , Janus Kinase 3 , Mice , Oxyquinoline/chemistry , Phosphorylation/drug effects , Protein Binding , Protein Structure, Tertiary , Protein-Tyrosine Kinases/metabolism , Signal Transduction/drug effects , Structure-Activity Relationship
2.
Bioorg Med Chem Lett
; 13(18): 3111-4, 2003 Sep 15.
Article
in English
| MEDLINE
| ID: mdl-12941345
ABSTRACT
A series of oxindoles demonstrating inhibition of the phosphorylation of biotinylated substrates of Syk and IgE/Fc epsilon RI triggered basophil cell degranulation has been identified. A study of the SAR around sulfonamide 31 (IC(50)=5 nM, EC(50)=1400 nM) is discussed. The modest cellular activity representative of the sulfonamide series was overcome when the Polar Surface Area was lowered to <110 A(2), leading to the identification of amide 32 (IC(50)=145 nM, EC(50)=100 nM).
