Bioorganic & Medicinal Chemistry Letters 2008-04-01

Design and synthesis of a pyrido[2,3-d]pyrimidin-5-one class of anti-inflammatory FMS inhibitors.

Hui Huang, Daniel A Hutta, Huaping Hu, Renee L DesJarlais, Carsten Schubert, Ioanna P Petrounia, Margery A Chaikin, Carl L Manthey, Mark R Player

Index: Bioorg. Med. Chem. Lett. 18(7) , 2355-61, (2008)

Full Text: HTML

Abstract

A series of pyrimidinopyridones has been designed, synthesized and shown to be potent and selective inhibitors of the FMS tyrosine kinase. Introduction of an amide substituent at the 6-position of the pyridone core resulted in a significant potency increase. Compound 24 effectively inhibited in vivo LPS-induced TNF in mice greater than 80%.