title: Imidazo[4,5-d]thiazolo[5,4-b]pyridine based inhibitors of IKK2: synthesis, SAR, PK/PD and activity in a preclinical model of rheumatoid arthritis.
abstract: The synthesis, structure-activity relationships (SAR) and biological evaluation of thiazole based tricyclic inhibitors of IKK2 are described. Compound 9 was determined to be orally efficacious in a murine model of rheumatoid arthritis.
authors.affiliation: Bristol-Myers Squibb, Research and Development, Princeton, NJ 08543-4000, USA. alaric.dyckman@bms.com
authors.forename: Alaric J
authors.initials: AJ
authors.lastname: Dyckman
authors.forename: Charles M
authors.initials: CM
authors.lastname: Langevine
authors.forename: Claude
authors.initials: C
authors.lastname: Quesnelle
authors.forename: James
authors.initials: J
authors.lastname: Kempson
authors.forename: Junqing
authors.initials: J
authors.lastname: Guo
authors.forename: Patrice
authors.initials: P
authors.lastname: Gill
authors.forename: Steven H
authors.initials: SH
authors.lastname: Spergel
authors.forename: Scott H
authors.initials: SH
authors.lastname: Watterson
authors.forename: Tianle
authors.initials: T
authors.lastname: Li
authors.forename: David S
authors.initials: DS
authors.lastname: Nirschl
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Gillooly
authors.forename: Mark A
authors.initials: MA
authors.lastname: Pattoli
authors.forename: Kim W
authors.initials: KW
authors.lastname: McIntyre
authors.forename: Laishun
authors.initials: L
authors.lastname: Chen
authors.forename: Murray
authors.initials: M
authors.lastname: McKinnon
authors.forename: John H
authors.initials: JH
authors.lastname: Dodd
authors.forename: Joel C
authors.initials: JC
authors.lastname: Barrish
authors.forename: James R
authors.initials: JR
authors.lastname: Burke
authors.forename: William J
authors.initials: WJ
authors.lastname: Pitts
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D004195:Disease Models, Animal; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D005260:Female; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007093:Imidazoles / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011725:Pyridines / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D051381:Rats; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry*
chemical_list: D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D013844:Thiazoles; C029899:imidazole; D051550:I-kappa B Kinase