title: Ruthenium half-sandwich complexes as protein kinase inhibitors: an N-succinimidyl ester for rapid derivatizations of the cyclopentadienyl moiety.
abstract: Cyclopentadienyl half-sandwich ruthenium complexes have been demonstrated to be promising scaffolds as protein kinase inhibitors. In order to rapidly identify derivatives which display modified pharmacological properties, we developed the synthesis of an organoruthenium compound bearing an N-succinimidyl ester at the cyclopentadienyl moiety. The quenching of this activated ester with a library of primary amines, followed by testing of the resulting amide library, led to the identification of organometallic Pim-1 and GSK-3 inhibitors with improved potencies and kinase selectivities. [structure: see text].
authors.affiliation: University of Pennsylvania, Department of Chemistry, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Howard
authors.initials: H
authors.lastname: Bregman
authors.forename: Eric
authors.initials: E
authors.lastname: Meggers
mesh_terms: D000588:Amines / Q000138:chemical synthesis; D002851:Chromatography, High Pressure Liquid; D003517:Cyclopentanes / Q000737:chemistry*; D004952:Esters / Q000737:chemistry*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors; D007700:Kinetics; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D051573:Proto-Oncogene Proteins c-pim-1 / Q000037:antagonists & inhibitors; D017975:Ruthenium Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D013237:Stereoisomerism; D013379:Substrate Specificity; D013388:Succinimides / Q000737:chemistry*
chemical_list: D000588:Amines; D003517:Cyclopentanes; D004952:Esters; D047428:Protein Kinase Inhibitors; D017975:Ruthenium Compounds; D013388:Succinimides; D051573:Proto-Oncogene Proteins c-pim-1; D038362:Glycogen Synthase Kinase 3