title: Inhibition of Tpl2 kinase and TNF-alpha production with 1,7-naphthyridine-3-carbonitriles: synthesis and structure-activity relationships.
abstract: The synthesis and structure-activity studies of a series of 6-substituted-4-anilino-[1,7]-naphthyridine-3-carbonitriles as inhibitors of Tpl2 kinase are described. The early exploratory work described here may lead to the discovery of compounds with significant therapeutic potential for treating rheumatoid arthritis and other inflammatory diseases.
authors.affiliation: Chemical and Screening Sciences, Wyeth Research, 200 Cambridge Park Drive, Cambridge, MA 02140, USA.
authors.forename: Lori Krim
authors.initials: LK
authors.lastname: Gavrin
authors.forename: Neal
authors.initials: N
authors.lastname: Green
authors.forename: Yonghan
authors.initials: Y
authors.lastname: Hu
authors.forename: Kristin
authors.initials: K
authors.lastname: Janz
authors.forename: Neelu
authors.initials: N
authors.lastname: Kaila
authors.forename: Huan-Qiu
authors.initials: HQ
authors.lastname: Li
authors.forename: Steve Y
authors.initials: SY
authors.lastname: Tam
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Thomason
authors.forename: Ariamala
authors.initials: A
authors.lastname: Gopalsamy
authors.forename: Greg
authors.initials: G
authors.lastname: Ciszewski
authors.forename: John W
authors.initials: JW
authors.lastname: Cuozzo
authors.forename: J Perry
authors.initials: JP
authors.lastname: Hall
authors.forename: Sang
authors.initials: S
authors.lastname: Hsu
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Telliez
authors.forename: Lih-Ling
authors.initials: LL
authors.lastname: Lin
mesh_terms: D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors*; D009287:Naphthyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D009570:Nitriles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D009287:Naphthyridines; D009570:Nitriles; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D014409:Tumor Necrosis Factor-alpha; D020930:MAP Kinase Kinase Kinases; C069937:MAP3K8 protein, human