Abstract
The discovery of novel 5,7-disubstituted[1,6]naphthyridines as potent inhibitors of Spleen Tyrosine Kinase (SYK) is discussed. The SAR reveals the necessity for a 7-aryl group with preference towards para substitution and that this in combination with 5-aminoalkylamino substituents further improved the potency of the compounds. The initial SAR as well as a survey of the other positions is discussed in detail.
MeSH terms
-
Animals
-
Enzyme Inhibitors / chemistry*
-
Enzyme Inhibitors / pharmacology*
-
Enzyme Precursors / antagonists & inhibitors*
-
Humans
-
Inhibitory Concentration 50
-
Intracellular Signaling Peptides and Proteins
-
Naphthyridines / chemistry*
-
Naphthyridines / pharmacology*
-
Protein-Tyrosine Kinases / antagonists & inhibitors*
-
Spleen / enzymology*
-
Structure-Activity Relationship
-
Syk Kinase
Substances
-
Enzyme Inhibitors
-
Enzyme Precursors
-
Intracellular Signaling Peptides and Proteins
-
Naphthyridines
-
Protein-Tyrosine Kinases
-
SYK protein, human
-
Syk Kinase