title: Organometallic Pyridylnaphthalimide Complexes as Protein Kinase Inhibitors.
abstract: A new metal-containing scaffold for the design of protein kinase inhibitors is introduced. Key feature is a 3-(2-pyridyl)-1,8-naphthalimide "pharmacophore chelate ligand" which is designed to form two hydrogen bonds with the hinge region of the ATP-binding site and is at the same time capable of serving as a stable bidentate ligand through C-H-activation at the 4-position of the electron-deficient naphthalene moiety. This C-H-activation leads to a reduced demand for coordinating heteroatoms and thus sets the basis for a very efficient three-step synthesis starting from 1,8-naphthalic anhydride. The versatility of this ligand is demonstrated with the discovery of a ruthenium complex that functions as a nanomolar inhibitor for myosin light-chain kinase (MYLK or MLCK).
authors.affiliation: Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Strasse, 35043 Marburg, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Blanck
authors.forename: Thomas
authors.initials: T
authors.lastname: Cruchter
authors.forename: Adina
authors.initials: A
authors.lastname: Vultur
authors.forename: Radostan
authors.initials: R
authors.lastname: Riedel
authors.forename: Klaus
authors.initials: K
authors.lastname: Harms
authors.forename: Meenhard
authors.initials: M
authors.lastname: Herlyn
authors.forename: Eric
authors.initials: E
authors.lastname: Meggers