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

…, M Hrapchak, AS Prokopowicz, DR Goldberg…

Index: Cywin, Charles L.; Zhao, Bao-Ping; McNeil, Daniel W.; Hrapchak, Matt; Prokopowicz III, 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. Bioorganic and Medicinal Chemistry Letters, 2003 , vol. 13, # 8 p. 1415 - 1418

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Citation Number: 52

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.