Title:Approaches to a Multitargeting Drug Development: First Profiled 3- Ethoxycarbonyl-1-aza-9-oxafluorenes Representing a Perspective Compound Class Targeting Alzheimer Disease Relevant Kinases CDK1, CDK5 and GSK-3β
Volume: 10
Issue: 1
Author(s): Andreas Hilgeroth, Volkmar Tell, Steffi Kramer, Frank Totzke and Christoph Schachtele
Affiliation:
Keywords:
Multitargeting, structure-activity relationships, biological activity, alzheimer disease, compound profiling, protein
kinases.
Abstract: Since Alzheimer disease (AD) is a multifactorial disease, recent therapeutical approaches concentrate on the
development of a multitargeting drug. Various protein kinases are known to be involved in the progression of AD. A first
series of 3-ethoxycarbonyl-1-aza-9-oxafluorenes has been synthesized and biologically evaluated as AD-relevant protein
kinase inhibitors. A concentration-dependent inhibition of important AD-relevant kinases has been characterized after the
selectivity of kinase inhibition had been demonstrated. Structure-activity relationships of protein kinase inhibition are discussed
and first multitargeting inhibitors have been identified.