Discovery and SAR of novel [1,6]Naphthyridines as potent inhibitors of spleen tyrosine kinase (SYK)

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...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2003-04, Vol.13 (8), p.1415-1418
Main Authors: Cywin, Charles L, Zhao, Bao-Ping, McNeil, Daniel W, Hrapchak, Matt, Prokopowicz, Anthony S, Goldberg, Daniel R, Morwick, Tina M, Gao, Amy, Jakes, Scott, Kashem, Mohammed, Magolda, Ronald L, Soll, Richard M, Player, Mark R, Bobko, Mark A, Rinker, James, DesJarlais, Renee L, Winters, Michael P
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - pharmacology
Enzyme Precursors - antagonists & inhibitors
Humans
Inhibitory Concentration 50
Intracellular Signaling Peptides and Proteins
Medical sciences
Miscellaneous
Naphthyridines - chemistry
Naphthyridines - pharmacology
Pharmacology. Drug treatments
Protein-Tyrosine Kinases - antagonists & inhibitors
Spleen - enzymology
Structure-Activity Relationship
Syk Kinase
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. Graphic
ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(03)00163-X