title: Design and preparation of 2-benzamido-pyrimidines as inhibitors of IKK.
abstract: The design, synthesis, and the biological evaluation of 2-benzamido-pyrimidines as novel IKK inhibitors are described. By optimization of the lead compound 3, compounds 16 and 24 are identified as good inhibitors of IKK2 with IC(50) values of 40 and 25 nM, respectively. Compound 16 also demonstrated significant in vivo activity in an acute model of cytokine release.
authors.affiliation: Novartis Institutes for BioMedical Research, CH-4002 Basel, Switzerland. rudolf.waelchli@novartis.com
authors.forename: Rudolf
authors.initials: R
authors.lastname: Waelchli
authors.forename: Birgit
authors.initials: B
authors.lastname: Bollbuck
authors.forename: Christian
authors.initials: C
authors.lastname: Bruns
authors.forename: Thomas
authors.initials: T
authors.lastname: Buhl
authors.forename: Jörg
authors.initials: J
authors.lastname: Eder
authors.forename: Roland
authors.initials: R
authors.lastname: Feifel
authors.forename: Rene
authors.initials: R
authors.lastname: Hersperger
authors.forename: Philipp
authors.initials: P
authors.lastname: Janser
authors.forename: Laszlo
authors.initials: L
authors.lastname: Revesz
authors.forename: Hans-Günter
authors.initials: HG
authors.lastname: Zerwes
authors.forename: Achim
authors.initials: A
authors.lastname: Schlapbach
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors*; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D016207:Cytokines; D004791:Enzyme Inhibitors; D011743:Pyrimidines; D051550:I-kappa B Kinase