title: Synthesis and biological evaluation of tricyclic anilinopyrimidines as IKKbeta inhibitors.
abstract: A series of tricyclic anilinopyrimidines were synthesized and evaluated as IKKbeta inhibitors. Several analogues, including tricyclic phenyl (10, 18a, 18c, 18d, and 18j) and thienyl (26 and 28) derivatives were shown to have good in vitro enzyme potency and excellent cellular activity. Pharmaceutical profiling of a select group of tricyclic compounds compared to the non-tricyclic analogues suggested that in some cases, the improved cellular activity may be due to increased clog P and permeability.
authors.affiliation: Chemical Sciences, Pfizer Global Research and Development, Collegeville, PA 19335, USA. aimeecrombie@hotmail.com
authors.forename: Aimee L
authors.initials: AL
authors.lastname: Crombie
authors.forename: Fuk-Wah
authors.initials: FW
authors.lastname: Sum
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Powell
authors.forename: Darrin W
authors.initials: DW
authors.lastname: Hopper
authors.forename: Nancy
authors.initials: N
authors.lastname: Torres
authors.forename: Dan M
authors.initials: DM
authors.lastname: Berger
authors.forename: Yixian
authors.initials: Y
authors.lastname: Zhang
authors.forename: Maria
authors.initials: M
authors.lastname: Gavriil
authors.forename: Tammy M
authors.initials: TM
authors.lastname: Sadler
authors.forename: Kim
authors.initials: K
authors.lastname: Arndt
mesh_terms: D000818:Animals; D002460:Cell Line; D002463:Cell Membrane Permeability; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors*; D020128:Inhibitory Concentration 50; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D011743:Pyrimidines; D051550:I-kappa B Kinase