title: Design and synthesis of 6,6-fused heterocyclic amides as raf kinase inhibitors.
abstract: Compounds belonging to several scaffolds-quinazolines, quinolines and quinoxalines-were designed and synthesized as Raf kinase inhibitors. Scaffolds were assessed for in vitro Braf(V600E) inhibition, and overall kinase selectivity. Pharmacokinetic parameters for one of the scaffolds were also determined.
authors.affiliation: Global Discovery Chemistry/Oncology & Exploratory Chemistry, Novartis Institutes for Biomedical Research, Emeryville, CA 94608, USA. savithri.ramurthy@novartis.com
authors.forename: Savithri
authors.initials: S
authors.lastname: Ramurthy
authors.forename: Abran
authors.initials: A
authors.lastname: Costales
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Jansen
authors.forename: Barry
authors.initials: B
authors.lastname: Levine
authors.forename: Paul A
authors.initials: PA
authors.lastname: Renhowe
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Shafer
authors.forename: Sharadha
authors.initials: S
authors.lastname: Subramanian
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D002478:Cells, Cultured; D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D048490:raf Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D048490:raf Kinases